Since anti vascular endothelial growth factor (VEGF) therapy has recently become the first-line treatment of wet age related macular degeneration in China,as well as retinopathy of prematurity,neovascular glaucoma and macular edema secondary to diabetic retinopathy or retinal vein occlusion in other countries,It is worth thinking about that how to perform anti-VEGF treatment properly to benefit more patients.We reviewed the fields of clinical researches to explore the best role of anti-VEGF treatment in prevention and treatment of retinal disease in future.

There are lots of imaging technologies in the ocular fundus disease field,including ultrasound biomicroscopy (UBM),fundus fluorescein angiography (FFA),indocynine green angiography (ICGA),fundus photograph (FP) and Optical Coherence Tomography (OCT).However there is no standard for image formats among various fundus imaging equipment,technology application processes,thus the relevant data cannot be compared and analyzed.And improper operation of the instruments causes unstable image quality or image missing.Also lack of appropriate evaluation guidelines results in different interpretation of same image data.These three factors not only affect the fundus imaging device application efficiency,limit the sharing of fundus imaging resource,but also hinder the development of fundus imaging diagnostic applications.Therefore,instrument types,data acquisition protocol and data presenting formats should be standardized for ocular fundus image acquisition.The technicians who operate the machine should be trained regularly to follow the standard operating procedure of data acquiring,thus to ensure integrity,truthful and reliable data is collected.In order to enhance the application efficiency of fundus imaging equipment,save public health resources,to promote fundus imaging diagnostic technology development,we need to develop evaluation guidelines for fundus image data,establish a comprehensive system including remote consultation center,reading center and quality control center.

Although there are numerous case resource,there still exist a relatively long distance in clinical research in China in comparison with developing countries because of inadequate recognition and funding,which has greatly affected the development of standardization of clinical medical in China for the past few decades.With the deepening of recognition and increasing of special support to clinical medical research in China,the development based on clinic research will face new opportunities.As a result,it is necessary for ophthalmologists to explore clinical issues,leverage from the mega trend of clinical research and deliver high-quality results.To achieve this goal,ophthalmologists will have to constantly update their knowledge base,standardize clinical practice and improve diagnosis methods.So far,challenges persist in clinical research in ophthalmology as follows:It is difficult to get funding for clinical research project;It is difficult to get ethnics approval for clinical research project;The research design for forward-looking projects is yet to be standardized;Cross-disciplinary collaboration needs to be enhanced.This review was expected to inspire more attention from clinical research specialists and consequently more highquality clinical studies.

As a potent collagenase activator,ocriplasmin is a recombinant truncated form of serine protease that retains the protease activity of plasmin.Pre-clinical animal experiments,clinical trials and recent clinical studies all indicated a promising outcome of intravitreal injection of ocriplasmin to treat vitreomacular interface diseases,including vitreomacular adhesion (VMA),vitreomacular traction (VMT) and full-thickness macular hole.Ocriplasmin was approved by the Food and Drug Administration of USA in the management of symptomatic VMA,and by the European Medicines Agency in treating VMT-associated macular hole with less than or equal 400 pm.Further randomized controlled clinical trials are needed for further comprehensive observation and evaluation on its efficiency,safety and other noteworthy issues.

The pathogenesis of diabetic retinopathy (DR) is more complex. For the upstream of traditional pathogenesis, to looking for unifying mechanism theory which proposed in foundation of common promoters and the latest view of DR may be the result of chronic inflammation. Both of them provide the basic and clinical theraby of DR with new direction. Therefore, there are many related issuess till needs to intensive study.

OBJECTIVE:To observe the effect of the combination of propofol and midazolam on learning memory of mice.METHODS:Fifty mice were divided into 5 groups(n=10):NS group(normal saline,subcutaneously),LM group(10% intralipid,peritoneal),MZ group(1 mg?kg-1 midazolam,subcutaneously),PP group(20 mg?kg-1 propofol,peritoneal) and MP group(combination of 0.5 mg?kg-1 midazolam and 10 mg?kg-1 propofol).Latency and error times in each group were observed by step-down test and step-through test so as to evaluate the effect of medicine on learning memory of mice.RESULTS:On the 1st and 2nd day after medication,significant differences were noted in error times and latency in MP group,PP group and MZ group,as compared with NS group and LM group(P0.05).Compared with MZ group,reduction of error times and prolongation of latency were noted in MP group and PP group on the 2nd day after medication(P0.05).CONCLUSION:Combination of propofol and midazolam(half dose) can result in hypofunction of learning memory of mice as well as they are used alone.Synergistic action is performed between propofol and midazolam.

The therapeutic response of anti-vascular endothelial growth factor (VEGF) differs among individuals.According to the changes of central retinal thickness,intraretinal fluid,subretinal fluid,best corrected visual acuity and other morphological or functional manifestations after treatment,the performance of the treated eyes can be classified as optimal response,poor response and non-response.A variety of factors could account for poor or non-response to anti-VEGF,such as genomic polymorphism and specific genomic risk alleles,lesion characteristics,vitreous and macular structural abnormalities,resistance to anti-VEGF drug,and the role of pericytes and others.The common counter measures include increasing the dosage,shortening the injection interval and replacing with another alternative drug,inhibition of pericytes,relieving vitreomacular anatomical abnormalities.It is still worthy of further exploration that how to assess individual reasons for non-response,so that we can give proper treatment to reduce the excessive use of anti-VEGF drugs and improve the clinical management of ocular neovascularization diseases.

Retinal neuronal cells are crucial in the formation of vision.Injury or death of these cells may lead to irreversible damage to visual function due to their low regenerative capacity.The P2X7 receptor is a trimeric adenosine triphosphate (ATP)-gated cation channel.Recent studies have shown that P2X7 receptor plays a role in retinal neuronal death.In a series of animal models,when exposed to conditions of hypoxia or ischemia,elevated ocular pressure,trauma and exogenous agonists,P2X7 receptor activated by extracellular ATP can cause death of retinal neuronal cells such as retinal ganglion cells and photoreceptor cells through direct or indirect pathways.Blocking the expression and function of P2X7 receptor by its specific antagonist and gene knocking-out,the loss of retinal neuronal cells is significantly attenuated.P2X7 receptor may become a potential novel neuroprotective target for diseases related to the loss of retinal neurons.

Diabetic macular edema (DME) is thickening retina with two disc diameter,which is the leading cause of blindness in diabetic retinopathy patients.The initial studies demonstrated that laser treatment of DME prevented further visual deterioration but did not improve visual acuity.Although glucocorticoid slow-release system can extend the time of effective drug concentration,to help glucocorticoid better carry out its biological effect,further studies are needed to warrant their safety due to increasing intraocular pressure and cataract progression.Novel studies identifying the presence of vascular endothelial growth factor (VEGF) in the eye with DME allowed for the development of an alternative anti-VEGF therapy,which revolutionized the management of DME by not only preventing vision loss,but also improving overall vision.Anti-VEGF therapy is becoming the first-line treatment of DME.However,present treatment modalities including anti-VEGF for DME had limitations,which build on the current understanding of DME pathogenesis.Further in-depth study of the development and outcome of DME is needed to optimize the therapeutic schemes,based on objective and scientific observation of treatment response.Finally we need to fully utilize the public health services and clinical management resources for diabetic patients,to prevent the visual impairment of DME before its occurrence.

Diabetic macular edema (DME) is a common ocular complication of diabetes patients.It mainly involve macular which is closely related with visual function,thus DME is one of the major reasons causing visual impairment or blindness for diabetes patients.How to reduce the visual damage of DME is always a big challenge in the ophthalmic practice.In the past three decades,there are tremendous developments in DME treatments,from laser photocoagulation,anti-inflammation drugs to anti-vascular endothelial growth factor therapy.However,the mechanism of DME development is not yet completely clear; every existing treatment has its own advantages and weaknesses.Therefore DME treatment still challenges us to explore further to reduce the DME damages.