Dry eye is the most common eye illness which manifests as a chronic inflammation on ocular surface and imposes significant threat to vision. Though dry eye is high prevalent, specific medication to treat this refractory disorder is very limited. The paucity of new drugs available can be attributed to wide range of severity distribution as well as lack of appropriate animal model. Animal disease model plays a significant role in preclinical drug screening and testing prior to clinical trial. Various techniques have been explored to create dry eye models for drug testing,including surgical removal of lacrimal gland,systemic or local drug induction,autoimmune eliciting,and genetic manipulation. This article reviewed the important dry eye models and their roles in development of dry eye drugs to provide insight and inspiration for clinicians and researchers.

Age.related macular degeneration ( AMD ) is the primary cause of the blindness among the population aged more than 50 years old. The prevalence of AMD increases with age growing. Wet AMD is the main cause of the visual impairment in over 90％ of AMD patients, which is characterized by formation of choroidal neovascularization. It takes the hypersecretion of vascular endothelial growth factor ( VEGF) as a mechanism,leading to vision loss and blindness finally. Targeted anti.VEGF therapy for angiogensis,like ranibizumab and aflibercept can reduce the rate of blindness greatly in AMD patients. It has become the front.line therapy in clinical. However,there still exist some problems. Some patients do not respond to the treatment or their eyesight cannot sustain after long.term treatment. In addition,repeated injection increases the risk of complications and economic burden. In order to further increase their quality of life and improve long.term outcome in patients with wet AMD,a steady flow of new therapy has emerged, such as function towards the same or different targets of antiangiogenesis to enhance the effect by combination therapy,improving or simplifying the mode of administration,inhibiting VEGFR tyrosine protein kinase, etc. This paper reviewed the research progress of anti.VEGF for the therapy in wet AMD.

The application of antiglaucoma drugs is the main treatment for glaucoma,but there are differences in the response of patients to antiglaucoma drugs. Different races have different reactivities to prostaglandins;the same patient may has different reactivity to different prostaglandins;with the prolonged use of prostaglandins,the status of some patients have changed from being unresponsive to being reactive. The reasons for individual difference of drug response are complex. Drug receptor and metabolism gene polymorphisms are deemed as the cause of individual difference. Studying the relationship between drug responses and gene differences can realize individual therapy. This review summarized the response to antiglaucoma drugs and influence factors leading to individual difference of drug response,which may provide help for clinical individualized and precise treatment.

Neuromyelitis optica ( NMO ) is an autoimmune, demyelinating disease of the central nervous system manifesting with optic neuritis and longitudinally extensive transverse myelitis. Aquaporin.4 ( AQP4 ) .IgG is currently regarded as a specific biomarker of NMO. Nevertheless,AQP4.IgG seronegativity in 10％-25％ of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis. In this article,we reviewed current knowledge about biomarkers of NMO from AQP4, myelin.oligodendrocyte glycoprotein, AQP1 and glial fibrillary acidic protein,providing a new insight in the diagnosis of NMO.

Anti-vascular endothelial growth factor (VEGF) therapy is a major strategy for treating ocular neovascular diseases nowadays.It has revolutionarily improved the vision of many patients since its emergence.However,VEGF is essentially a protective growth factor that is compensatorily produced by human body.In the anti-VEGF treatment of the diseases,the physiological effects of VEGF are also inhibited,which may result in some related problems,such as retinal atrophy,retinal pigment epithelium (RPE) tears,systemic adverse effects,and so on.Retinal atrophy has become one of the major causes of visual loss in the late stage of the treatment.The specific mechanism underlying them is not completely known,we should pay enough attention to them.How to improve the anti-VEGF treatment strategy in order to reduce the incidence of these problems will be a great challenge.

Objective To study the structural changes of retinal microcirculation in mouse model of ischemia reperfusion injury(RIR).Methods Ninty healthy male C57BL/6 mice were devided into normal group and RIR group by using random number table method,45 mice for each group.The left eyes in both groups were used in this study.The mouse model of RIR was established by perfusion of saline solution in the anterior chamber.The damage of microcirculation was analyzed from different levels of vascular structure and function by retinal blood vessel staining,FITC angiography,histopathological examination,and ultrostructure of retinal vessels was observed with transmission electron microscope.The experimental animals and experimental conditions complied with the Regulations on the Management of Laboratory Animals of Kunming Medical University.Results There was no significant difference in retinal arterioles diameter in the RIR group compared to the normal control group (P=0.350).The small veins were obviously dilated in comparison with normal control group (P =0.03) and were in hyper-congestive state.The artery/vein value was 0.76±0.03 in the RIR group,and that in the normal control group was 0.97±0.01,with significant difference between them (P=0.000).The main changes were capillary occlusion,non-perfusion zone formation and other structural changes,accompaning by blood-retinal barrier damage;the destruction of capillary endothelial cells and pericytes and basement membrane thickening were seen under the transmission electron microscope.Conclusions RIR mainly results in capillary damage,including capillary barrier damage,capillary occlusion and non-perfusion area formation.

Objective To investigate the regulation effects of Ngn2 gene transfection on retinal neuron differnetion in three-dimentional optic vesicle (OV) of mice.Methods OV was cultured in vitro using mouse induced pluripotent stem cells (iPSC) under specific conditions.During OV culture,it was transfected multiple times by lentivirus-mediated Ngn2 gene and then it was induced after maturation.The cells were specificly differentiated toward retinal nerve cells in OV.Using the green fluorescent protein (EGFP) gene as control,the differentiation of retinal nerve cells in OV was detected by immunohistochemistry.Reverse transcription PCR and Western blot were used to quantitatively detect the expressions of retinal neuron-specific proteins Pax6,Islet1 and Brn3b.Results The mouse iPS-derived OV was successfully cultured.The number of neural cells in the OV transfected with the Ngn2 gene was increased by the lentiviral-mediated lentivirus.The expressions of PAX6,Islet1 and Brn3b in the Ngn2 transfection group were significantly higher at the gene and protein levels than those in the control group,with significant differences between the two groups (P＜0.05).Conclusions The Ngn2 gene can effectively increase the number of retinal neuron differentiation in OV and make in vitro cultured OV more mature and form a more perfect retinal cell neural circuit.

Objective To analyze the clinical features of paracentral acute middle maculopathy(PAMM).Methods A retrospective series case observation was carried out.Clinical data of 11 eyes from 11 patients with PAMM were included in this study from January 2016 to December 2017 in Henan Eye Hospital.All of the patients received general information inquiry,regular ophthalmic examination,color fundus photography,fundus infrared imaging (IR),spectral-domain optical coherence tomography (SD-OCT),OCT angiography (OCTA),fundus fluorescence angiography(FFA),visual field examination and multifocal electroretinography.Results The ages of the patients ranged from 50 to 71 years old,with the average age of 60 years old.There were 9 males and 2 females,including hypertension in 3 patients,hypertension carotid atherosclerotic plaque in 1 patientd,diabetes with carotid stenosis in 2 patients,hypertension with diabetes in 2 patients,only carotid atherosclerotic plaque in 2 patients and chest trauma in 1 patient.The symptoms of PAMM were central or paracentral scotoma within 1 week.The best corrected visual acuity(BCVA) of the patients ranged from 0.6 to 1.0.All of the patients had central or paracentral scotoma or decrease of visual sensitivities.Mf-ERG showed that amplitude density of P1 waves was reduced in 8 eyes.With subtle-white lesion was seen in fundus of 8 eyes and no obvious symptom in 3 eyes.IR imaging demonstrated hypo-reflection in paracentral macula area in all eyes,and their FFA imaging seemed normal.SD-OCT scanning across lesion area revealed hyper-reflection in inner nuclear layer (INL).OCTA demonstrated perfusion deficit in deep capillary plexuses(DCP).After treatment,there was no improvement in BCVA for all the eyes but scotomas were lessened.Conclusions PAMM easily occurs in older males with systemic diseases.PAMM lesson is a occult paramacular middle layer of retinopathy.The combination examination of morphological and functional methods is avaiable for diagnosis.

Objective To investigate the changes of metamorphopsia between before and after surgery in the patients with idiopathic epiretinal membrane and its influence factors.Methods A series cases observitional study included 39 eyes of 39 patients with idiopathic epiretinal membrane.Follow-up was carried out at 1 week before surgery and 3,6 months after surgery respectively.M-chart was used to quantify the severity of metamorphopsia (M-score).EDTRS visual chart was used to quantify best corrected visual acuity (BCVA) (converted to LogMAR).Central subfield thickness (CST),central foveal volumn (CV),cube average thickness (CAT),central foveal thichness (CFT),ganglion cell layer (GCL) thickness,inner nuclear layer (INL) thickness,outer nuclear layer (ONL) and outer plexiform layer (OPL) thickness,the integrity of external limiting membrane,ellipsoid zone and interdigitation zone were analyzed by using spectral domain-optical coherence tomography (OCT).This study protocol was approved by Ethic Committee of Beijing Tongren Hospital (No.TRECKY-012).Written informed consent was obtained from each subject before surgery.Results Mean M-score was significantly decreased from 0.8 (0.3,1.1) before surgery to 0.5 (0.2,0.8) at 3 months after surgery,with a significant difference between the two time points (Z=-2.013,P=0.044).Mean M-score was 0.6(0.2,0.8) at 6 months after surgery,which was not significantly different in comparison with before surgery and 3 months after surgery (Z =-1.873,P =0.061;Z =-0.288,P =0.773).Compared with before surgery,the horizontal M-score was significantly decreased 3 months and 6 months after surgery (Z =-2.329,P =0.020;Z =-2.858,P =0.004).No significant difference was found in vertical M-score among before surgery and 3,6 months after surgery (all at P＞0.05).The BCVA was improved from 0.40 (0.30,0.66) before surgery to 0.20 (0.06,0.42) 3 months after surgery and declined to 0.30 (0.10,0.52) at 6 months after surgery,and significant differences were obtained between 3 months after surgery and before surgery or 6 months after surgery (Z =-4.087,P＜0.001;Z =-2.235,P =0.025).Compared with before surgery,the BCVA in cataract combined with vitrectomy operative group was significantly improved in 3 months and 6 months after surgery (Z=-2.613,P=0.009;Z=-2.466,P=0.014) and the BCVA in only vitrectomy group was significantly improved at 3 months after surgery but decreased 6 months after surgery,showing significant differences between 3 months after surgery and before surgery or 6 months after surgery (Z =-3.104,P =0.002;Z =-3.464,P =0.001).Preoperative M-score was positively correlated with preoperative BCVA,preoperative CST or preoperative CFT (rs =0.384,P =0.016;rs =0.585,P＜0.001;rs =0.601,P＜0.001).No correlation was found between BCVA with GCL,INL or ONL + OPL thickness.Horizontal M-score was positively correlated with CST,postoperative CV and postoperative CAT (rs=0.322,P=0.045;rs=0.340,P=0.034;rs =0.336,P=0.036),and no correlation was found between horizontal M-score and BCVA,CFT,GCL thickness,INL thickness,ONL+OPL thickness in 6 months after surgery.The vertical M-score and mean M-score were not correlated with OCT parameters in 6 months after surgery.The mean M-score was positively correlated with preoperative mean M-score,preoperative CST,preoperative CV,preoperative CAT in 6 months after surgery (rs =0.589,P＜0.001;rs =0.330,P =0.040;rs =0.404,P =0.011;rs =0.410,P =0.009).In addition,and no significant correlation between mean M-score and preoperative BCVA,CFT,GCL thickness,INL thickness,ONL+OPL thickness.Multivariate stepwise linear regression showed that preoperative M-score was a predictor of postoperative M-values (adjusted R2 =0.211,P =0.002).Conclusions Most metamorphopsia can be alleviated after idiopathic epiretinal membrane surgery.The residue metamorphopsia after surgery probably is correlated with preoperative metamorphopsia and CFT.

Objective To investigate the multimodal imaging characteristics of central serous chorioretinopathy (CSC) converted to polypoidal choroidal vasculopathy (PCV) and pachychoroidal neovascularization(PNV).Methods A retrospective case series study was adopted.The clinical data of 91 eyes from 79 patients with CSC who received treatment from June 2009 to September 2017 in Shenzhen Eye Hospital were analyzed.Color fundus photography,fundus fluorescein angiography (FFA),spectral domain optical coherence tomography (SD-OCT) and indocyanine angiography (ICGA) were performed in the patients.The eyes with recurrence or maintained serous retinal pigment epithelium (RPE) after treatment were examined once more.Results In 91 eyes,11 eyes of 9 patients converted to PNV.Late stage of FFA showed multifocal hyperfluorecnece in macular area.ICGA showed plaque hyperflurorescence overlying dilated choroidal vessel.OCT revealed irregular flap shallow RPE detachment with retinal neurosensory detachment.OCTA revealed mass-like enlarged choroidal vessel between RPE and Bruch membrane.Nine eyes of 7 patients with CSC converted to PCV,and late stage of FFA showed serous-hemorrhage pigment epithelium detachment(PED) and multifocal enlargement hyperfluorecnece.ICGA showed branch vessels network (BVN) with small polyps.OCT revealed PED like thumb with double-layer sign and retinal neurosensory detachment.OCTA en-face revealed BVN with small polyps at choroidal capillaries layer.The baselines BCVA of PCV and PNV (LogMAR) was 0.282±0.220 and 0.413±0.190,respectively with a significant difference between them (t =0.037,P ＜ 0.05).Subfoveal choroidal thickness (SFCT) of CSC,PCV and PNV patients was (373.61 ±65.11),(296.22 ±30.24) and (328.63 ±76.18) μm,with siginificant differences among them (F =3.48,both at P＜0.05).SFCT of PNV patients was thicker than that of PCV patients,with a significant difference between the two groups (t =2.91,P＜0.05).Conclusions Chronic or recurrence CSC is probably to develop to PNV,and the PNV with serous or hemorrhage PED is probably to switch to PCV.Multimodal imaging examination is helpful to the diagnosis of PNV and PCV.