Clinical efficacy and drug resistance of anti-epidermal growth factor receptor therapy in colorectal cancer

Colorectal cancer(CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC(mCRC), such as monoclonal antibodies against epidermal growth factor receptor(anti-EGFR), which provided additional clinical benefits in mCRC. However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated mCRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because; approximately fifty percent(40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet. Current article summarizes the clinical efficacy of anti-EGFR therapies and also evaluates its resistance mechanisms.

The effects of anti-vascular endothelial growth factor agents on human retinal pigment epithelial cells under high glucose conditions

AIM： To investigate the effects of high glucose levels and anti-vascular endothelial growth factor（VEGF） agents（bevacizumab,ranibizumab and aflibercept） on retinal pigment epithelium（RPE） cells.METHODS： ARPE-19 cells were cultured at different glucose levels（5.5 mmol/L,25 mmol/L,and 75 mmol/L）.Cell viability was evaluated by MTT assay at 3d after treatment with D-glucose.Cell migration ability was measured by wound healing assay at 3d.A cell death detection kit was used to assess apoptosis at 3 and 14 d.Cell proliferation was assessed by EdU assay at 3d.The culture medium was treated with anti-VEGF agents at clinically relevant concentrations.The experiment was then repeated at a different glucose level.RESULTS： The viability and migration of ARPE-19 cells were significantly decreased in the presence of 75 mmol/L as compared to 5.5 mmol/L glucose.The percentage of TUNEL-positive cells was significantly increased and the proliferative potential was decreased with 75 mmol/L compared to 5.5 mmol/L glucose.There were no significant differences in the results between 25 mmol/L and 5.5 mmol/L glucose.In the presence of 75 mmol/L glucose,the groups treated with anti-VEGF showed decreased cell viability and proliferation and increased apoptosis.However,there were no significant differences between the anti-VEGF groups.CONCLUSION： High glucose level decreases the viability,wound healing ability,and proliferation of RPE cells,while increasing apoptosis.Furthermore,anti-VEGF agents interfered with the physiological functions of RPE cells under high-glucose conditions,accompanied by decreases in cell viability and proliferation.

Numerical simulation of inhibiting effects on solid tumour cells in anti-angiogenic therapy: application of coupled mathematical model of angiogenesis with tumour growth

To investigate the inhibiting effects of the anti-angiogenic factor andostatin and the anti-angiogenic drug endostatin on turnout angiogenesis and turnout cells, a coupled mathematical model of tumor angiogenesis with tumour growth and blood perfusion is developed. Simulation results show that angiostatin and endostatin can improve the abnormal microenvironment inside the tumour tissue by effectively inhibiting the process of tumor angiogenesis and decreasing tumour cells. The present model can be used as a valid theoretical method in the investigation of the tumour anti-angiogenic therapy.

Bilateral same-session intravitreal injections of antivascular endothelial growth factors

AIMTo document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.

Supplementation of Yeast Extract to Practical Diet Improves the Growth, Anti-Oxidative Capacity and Intestinal Morphology of Shrimp Litopenaeus vannamei

Two control diets based on the commercial formula were designed to contain high(27%,D1)and low(22%,D2)levels of fish meal,respectively.Into D2,500,1000 and 1500 mg kg 1 of yeast extract were added,respectively,yielding three experimental diets(YE1 through YE3).Shrimp(initial body weight 0.30 g±0.02 g)were fed with the experimental diets,five tanks each diet and 30 shrimp individuals each tank,for 8 weeks,and then challenged with Vibrio parahaemolyticus.The results showed that the specific growth rate(SGR)of shrimp in D2 was significantly lower than that of shrimp in D1(P<0.05).The SGR of shrimp in YE3 was similar to that of shrimp in D1.The feed intake of shrimp was similar between D1 and D2.The feed conversion ratio and protein efficiency ratio of shrimp were similar among all diets(P>0.05).YE significantly improved the activity of glutathione S-transferase.The concentration of glutathione(GSH)and the total serum anti-oxidative capacity(T-AOC)of D1 were significantly higher than those of shrimp feeding other diets(P<0.05).The content of serum malondialdehyde of shrimp feeding YE2 and YE3 was signifi-cantly lower than that of shrimp feeding D2(P<0.05).The thickness of intestine muscular layer of shrimp feeding YE1 and YE2 was similar to that of shrimp feeding D1.The shrimp feeding YE1 showed the highest villus height of intestine among all groups.The cumulative mortality after challenging was similar among all groups(70.00%86.67%)(P>0.05).In conclusion,1000 1500 mg kg 1 of YE was suggested to be supplemented into the practical diets to improve the growth,anti-oxidative capacity and intestinal mor-phology of shrimp L.vannamei.

Diabetic macular edema:Efficacy and safety of antivascular endothelial growth factor therapy

Diabetic retinopathy is one of the prominent causes of vision impairment in the working-age population in industrialized countries and is related to 1%-5% of cases of blindness in the world. Among patients with diabetic retinopathy, diabetic macular edema(DME) is the major reason of vision impairment and represents a significant public health problem. Previous studies demonstrated the role of vascular endothelial growth factor(VEGF) in diabetic retinopathy and DME pathogenesis, and also revealed the efficacy of anti-VEGF agents for the management of these disorders. This review summarizes the outcomes of clinical studies that evaluated the anti-VEGF therapy including pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. A significant number of clinical trials indicated favorable functional and anatomical results of anti-VEGF therapy for DME. Therefore, these agents should be considered an option in the treatment of DME in routine clinical practice.

抗转化生长因子β_1(anti-TGF-β_1)对瘢痕成纤维细胞增殖和胶原合成的影响

目的 探讨抗转化生长因子β1(anti-TGF - β1)对瘢痕成纤维细胞增殖及胶原合成的影响及意义。方法 用电镜观察anti-TGF - β1作用后瘢痕成纤维细胞的形态学变化 ,以及用MTT法和3 H -脯氨酸掺入等方法检测anti-TGF - β1对体外培养的瘢痕成纤维细胞的增殖及胶原蛋白合成的影响。结果 anti -TGF - β1能明显影响成纤维细胞的超微结构 (细胞核、线粒体、粗面内质网等 )。anti -TGF - β1能抑制成纤维细胞的增殖和胶原蛋白的合成 (P <0 .0 1) ,在一定范围内 (10 μg/ml)呈剂量 -效应关系。抑制作用在 10 μg/ml时最大 ,抑制率达 72 %。结论 anti-TGF - β1能中和TGF - β1,促进成纤维细胞增殖和胶原合成的作用 ;提示anti-TGF - β1的应用可能为临床瘢痕的治疗提供新的途径。

Beyond KRAS:Predictive factors of the efficacy of anti-EGFR monoclonal antibodies in the treatment of metastatic colorectal cancer

Systematic analysis of the epidermal growth factor receptor(EGFR)pathway revealed that biomarkers could be used to predict the response to and outcome of antiEGFR therapies in patients affected by metastatic colorectal cancer.We have conducted a review on the most recent findings and advances on this topic.To this aim,we searched the PubMed database for articles devoted to predictive and prognostic biomarkers for patients administered cetuximab-and panitumumab-based therapies.Here we review the state of the art and the controversies about the molecular factors known to be predictors of the efficacy of anti-EGFR therapy,namely,KRAS,BRAF,NRAS,PI3KCA and PTEN,and we discuss their prognostic value in colorectal cancer patients.

Role of bevacizumab in colorectal cancer growth and its adverse effects:A review

Angiogenesis affects both wound healing and malignant cell growth through nutrients and oxygen.Vascular endothelial growth factor(VEGF) is the most important element involved in this complex process.Inhibition of VEGF influences angiogenesis and may restrict tumor growth and metastatic ability.Modern antiangiogenic therapy is based on this theory.Bevacizumab is a recombinant humanized monoclonal antibody(immunoglobulin G1) which binds with VEGF-A forming a large molecule.It can not be bound with VEGF tyrosine kinase receptors preventing VEGF-A incorporation;thus its activity is inhibited inducing blockage of VEGFmediated angiogenesis.Bevacizumab,in combination with chemotherapy or other novel targeted therapeutic agents,is currently used more frequently in clinical practice,mainly for managing advanced colorectal cancer.It is also used for managing other malignancies,such as breast cancer,pancreatic cancer,prostate cancer,non small-cell lung cancer,metastatic renal carcinoma and ovarian tumors.Although it is generally considered a safe treatment,there are reports of some rare side effects which should be taken into account.Recent experiments in rats and mice show promising results with a wider therapeutic range.

Vascular endothelial growth factor trap-eye(Aflibercept) for the management of diabetic macular edema

Diabetic retinopathy(DR)is the most common cause of visual loss among working age individuals.Diabetic macular edema(DME)is an important complication of DR that affects around one third of the patients with DR.Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor(VEGF)antagonists.The index review discusses aflibercept(EYLEA-Regeneron Pharmaceuticals,Inc.,Tarrytown,New York,NY,and Bayer Healthcare Pharmaceuticals,Berlin,Germany)in the context of other VEGF antagonists currently available for the treatment of DME.A systematic search of literature was conducted on PubMed,Scopus,and Google Scholar with no limitation on language or year of publication.Pre-clinical studies of aflibercept have shown a higher affinity of this molecule for vascular endothelial growth factor A(VEGF-A)along with a longer duration of action as compared to other VEGF antagonists.Recent clinical trials have shown visual outcome results for aflibercept to be similarly favorable as compared to other available agents with the added benefit of fewer required injections and less frequent monitoring.Aflibercept presents a potential exciting new addition to the armamentarium of current VEGF antagonists available for the treatment of DME and other retinal vascular diseases.However,further studies are indicated to confirm the role,safety,and efficacy of aflibercept for DME.

Intravitreal anti-VEGF agents, oral glucocorticoids, and laser photocoagulation combination therapy for macular edema secondary to retinal vein occlusion: preliminary report

AIM： To evaluate the efficacy and safety of combined anti-vascular endothelial growth factor （VEGF） agents, oral glucocorticoid, and laser photocoagulation therapy for macular edema （ME） secondary to retinal vein occlusion （RVO）. METHODS： This study included 16 eyes of 16 patients with RVO-associated ME. Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent. Two weeks later, patients underwent standard laser photocoagulation. Best-corrected visual acuity （BCVA）, central retinal thickness （CRT）, and retinal vessel oxygenation were examined over 12mo. RESULTS： Patients received 1.43＋0.81 anti-VEGF injections. Mean baseline and 12-month IogMAR BCVA were 0.96±0.51 （20/178） and 0.31±0.88 （20/40）, respectively, in eyes with central retinal vein occlusion （CRVO） （P〈0.00）, and 1.02±0.45 （201209） and 0.60±0.49 （20/80）, respectively, in eyes with branch retinal vein occlusion （BRVO） （P〈0.00）. At 12mo, CRT had significantly decreased in eyes with CRVO （P〈0.00） and BRVO （P〈0.00）. Venous oxygen saturation had significantly increased in eyes with CRVO （P〈0.00） and BRVO （P〈0.00）. No examined parameters were significantly different between the 2 RVO groups. No serious adverse effects occurred. CONCLUSION： Anti-VEGF, glucocorticoid, and photocoagulation combination therapy improves visual outcome, prolongs therapeutic effect, and reduces the number of intravitreal injections in eyes with RVO- associated ME.

A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers

Advances in molecular research in cancer have brought new therapeutic strategies into clinical usage.One new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) carcinomas.The concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new drugs.Type I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human malignancies.In this review,we focus on this promising therapeutic target,IGF-IR.The IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI cancers.Preclinical studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer treatments.These results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and pancreas.We also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical experiences.Several mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single agents.We summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug combinations.Thus,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcinomas.

Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers (mCRCs) addicted to epidermal growth factor receptor (EGFR) signalling.METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting mCRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science to identify eligible papers until March 21st, 2016 using these following terms: ‘‘colorectal cancer’’, “predictive biomarkers’’, “anti-EGFR therapy”, “KRAS”, “NRAS’’, “PIK3CA”, “TP53”, “PTEN”, ‘‘EGFR”, “MET”, “HER2”, “epiregulin”, “amphiregulin”, “prognostic biomarkers”, “BRAF”, “miRNA” and “antibody-dependent cell-mediated cytotoxicity (ADCC) activity”. Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and exclusion.RESULTS: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mCRCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mRNA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3CA. The prognostic value of selected microRNAs level and ADCC activity is under investigation, while the prognostic impact of BRAF status remains controversial.CONCLUSION: This review focuses on the personalized treatment of mCRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.

Dicranostigma leptopodum (maxim) fedde induced apoptosis in SMMC-7721 human hepatoma cells and inhibited tumor growth in mice

Dicranostigma Leptopodum (Maxim) Fedde (DL- F), which had been previously documented to suppress oxidative hemolysis of erythrocytes and enhance immune functions of murine peri- toneal macrophages, was investigated for its effect on anti-tumor activity. Of alkaloids extracted from DLF, five have been identified with employment of chromatographic analysis. An antiproliferative role of these alkaloids was determined on SMMC-7721 Human Hepatoma Ce- lls in an apoptosis-inducing manner, through MTT assaying, Trypan blue exclusion assaying and cytometric analysis of cell cycle distribution. To further examine their inhibitory effects on tumor progression, murine H22 cells were inoculated into Kunming mice to determine the role of these alkaloids of DLF in inhibiting tumor growth in the tumor-implanted mice. It was found that these alkaloids of DLF enhanced the tumor shrinkage effectively wherein its tumor inhibitory rate and immunohistochemistry stain- ing of the tumor were determined and profiled, respectively.

Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

AIM:To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS:Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and "high-grade" tumor budding was defi ned as 15 buds/high-power f ield.RESULTS: Tumor buds and K-RAS mutation both correctly classif ied 68% of patients. All patients with K-RAS mutation (n=7) or high-grade tumor budding (n=11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P=0.008)].CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting.

An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

AIM： To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema（DME） resistant to anti-vascular endothelial growth factor（VEGF） therapy.METHODS： Thirty-two DME patients were enrolled.A700 microgram slow release Intravitreal Dexamethasone Implant（Ozurdex~） was placed in the vitreous cavity.All patients were followed for 18 mo.Best-corrected visual acuity（BCVA） measured with Early Treatment Diabetic Retinopathy Study（ETDRS） and central macular thickness（CMT） exams were carried out at baseline（T0）and after 1（T1）,3（T3）,4（T4）,6（T6）,9（T9）,12（T12）,15（T15）,and 18mo（T18） post injection. RESULTS： Repeated measures ANOVA showed an effect of treatment on ETDRS（P〈0.0001）.Post hoc analyses revealed that ETDRS values were significantly increased at T1,T3,T4,T9,and T15（P 〈0.001） as compared to baseline value（T0）.At T6,T12,and T18,ETDRS values were still statistically higher than baseline（P〈0.001 vs T0）.However,at these time points,we observed a trend to return to baseline conditions.ANOVA also showed an effect of treatment（P 〈0.0001）.CMT decreased significantly at T1,T3,T4,T9,and T15（P〈0.001）.At T6（P〈0.01）,T12 and T18（P〈0.001） CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed.CONCLUSION： Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improveBCVA and CMT in DME patients resistant to anti-VEGF therapy.Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

Anti-angiogeneic Target Therapy for Cancer with Vaccine Based on the Recombinant Chicken FGFR-1 in Tumor-bearing Mice

To explore the anti-tumor effect of immunotherapy with recombinant protein vaccine based on FGFR-1 of chicken （cFR-1） in a mouse Meth A fibrosarcoma model, tumor volume and survival rate of the mice were observed at a 3-day interval. Microvessel density （MVD） was detected by immunohistochemistry. Auto-antibodies against self-FGFR-1 were detected by Western blotting and ELISA, respectively. The anti-FGFR-1 antibody-producing B cells （APBCs） were detected by enzyme-linked immunospot （ELISPOT） assay. Eighteen days after inoculation of tumor cells, the tumor volume was significantly smaller in cFR-l-immunized group than in mouse FGFR-1 （mFR-1） immunized group and normal saline （NS） control group （P〈0.05）, and the survival time was significantly longer in cFR-l-immunized group than in the control groups （P〈0.01）. MVD was significantly lower in cFR-l-immunized group than in mFR-1-immunized group and NS group （16.8 ±5.6 vs 64.6±1.8 and 59.6±8.7, P〈0.01）. Antibodies against self-FGFR-1 were found in mFR-1-immunized group, the major antibody subclasses were IgG1 and IgG2b. Compared with the two control groups, the numbers of APBCs in cFR-l-immunized group were significantly increased （P〈0.01） These results demonstrated that the cFR-1-related anti-angiogenesis protein vaccine could induce the production of auto-antibodies against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

Growth Performance of West African Dwarf (WAD) Sheep Fed Biodegraded <i>Enterolobium cyclocarpum</i>Based Diets

The performance and economics of production of West African Dwarf (WAD) sheep was investigated in an experiment that lasted for 70 days. Twelve male sheep averaging 9.9 kg in liveweight and aged 7 - 9 months were randomly assigned to four treatment groups in a completely randomized design with three animals per treatment. Chemical composition of diets, intake, liveweight gain and cost implication of feeding WAD sheep with grass, a conventional concentrate, an autoclaved and biodegraded Enterolobium cyclocarpum based diet were determined. The crude protein content of Guinea grass (4.43%) was relatively low compared to that of biodegraded Enterolobium cyclocarpum (14.13%). Total consumption and liveweight change were not significantly different (P 0.05). The growth rate of animals fed concentrates were significantly (P 0.05) higher than those on the grass diet. Cost per Kg of feed was the highest for control and least for guinea grass diet. However, cost per unit gain was the highest for Guinea grass diet (N176.73) and least for biodegraded Enterolobium cyclocarpum diet (N72.62). It was cheaper to produce 1 kg mutton using biodegraded EC diets than control, autoclaved and guinea grass diets respectively. The results suggest that biodegrading of Enterolobium cyclocarpum improved its nutrient quality, utilization and the performance and economy of production of West African Dwarf sheep.

Evaluation of Serum and Aqueous Humor Vascular Endothelial Growth Factor in Neovascular Glaucoma

Purpose: The study aimed to evaluate and correlate between the levels of vascular endothelial growth factor (VEGF) in serum and aqueous humor in cases of neovascular glaucoma (NVG) to stand up on if it can be used as a marker for early detection of such cases. Methods: This observational case control study included 60 eyes, divided into 3 groups, group A of 30 eyes presented by cataract of different causes (not diabetic patients and no signs of NVG) as a control group and group B of 30 eyes with NVG due to different causes, group C of the same eyes in group B but after one month of treatment by intravitreal bevacizumab and laser treatment by pan retinal photocoagulation (PRP). Serum VEGF was estimated in all groups, also aqueous humor VEGF was estimated in group A and B only. In addition glycosylated hemoglobin (HbA1c) was estimated in group B;statistical analysis of the results was performed. Results: The study revealed that the commonest cause of NVG was proliferative diabetic retinopathy (PDR) in 26 cases (86.7%), HbA1c in group B revealed mean value 7.68% ± 2.75%. Serum VEFG level in the group B of cases of NVG was significantly higher than the control group A (P 0.05). Conclusions: VEGF is considered a good marker for the NVG either in serum or aqueous humor, laser treatment and the use of anti-VEGF are crucial treatment for such cases, and also glycemic control is a must for regulation of the vascular process in diabetic patients for prevention of such ocular neovascularization.

Spontaneous or secondary to intravitreal injections of anti-angiogenic agents retinal pigment epithelial tears in age-related macular degeneration

·AIM:Toevaluatethevisualfunctionevolutionofretinal pigment epithelial(RPE) tears in patients with age-related macular degeneration(AMD) according to type of occurrence [spontaneous or secondary to anti-vascular endothelial growth factor(anti-VEGF) injection] and the topographic location of the tear after a two-year followup period.·METHODS: A total of 15 eyes of 14 patients with RPE tears in exudative AMD were analyzed retrospectively at the University Eye Clinic of Trieste. Inclusion criteria were: patient age of 50 or older with AMD and RPE tears both spontaneous occurring or post anti-VEGF treatment. Screening included: careful medical history,complete ophthalmological examination, fluorescein angiography(FA), indocyanine green angiography(ICG),autofluorescence and infrared imaging and optical coherence tomography(OCT). Patients were evaluated every month for visual acuity(VA), fundus examination and OCT. Other data reported were: presence of PED,number of injections before the tear, location of the lesion.·RESULTS:Meanfollow-up was24wk(SD±4wk). Atotal of 15 eyes were studied for RPE tear. In 6 cases(40%),the RPE tears occurred within two years of anti-VEGF injections the others occurred spontaneously. In 13cases(86.6%), the RPE tear was associated with pigment epithelial detachment(PED). In 7 cases(46.6%), the RPE tear occurred in the central area of the retina and involved the fovea. Two lesions were found in the parafoveal region, six in the extra-macular area. In all cases visual acuity decreased at the end of the follow-up period(P <0.01) independently of the type or the topographical location of the lesion.·CONCLUSION: RPE tear occurs in exudative AMD as a spontaneous complication or in relation to anti-VEGF injections. Visual acuity decreased significantly and gradually in the follow-up period in all cases. No correlation was found between visual loss and the type of onset or the topographic location of the tears.