Effects of three consecutive monthly intravitreal injection of ranibizumab for polypoidal choroidal vasculopathy in Korea

AIM: To evaluate the efficacy and safety of three consecutive monthly injections of intravitreal ranibizumab for the treatment of polypoidal choroidal vasculopathy(PCV) in Korea.METHODS: A retrospective chart review of 25 patients(27 eyes) with PCV was conducted. Patients received three initial monthly intravitreal injections(0.5 mg) of ranibizumab and were monitored monthly for 12 mo from January 2010 to October 2011. Reinjection of ranibizumab after three initial monthly loading was administered on an as-needed basis, guided by the optical coherence tomography(OCT), fluorescein angiography(FA) and indocyanine green angiography(ICGA). The main outcomes were the changes of the mean best corrected Snellen visual acuity(VA), central macular thickness(CMT) by OCT, the changes of polyps and branching vascular network by FA and ICGA, and total number of injections received by patients during the 12 mo.RESULTS: The mean best corrected Snellen visual acuities at baseline, 1, 3, 6 and 12 mo after primary injection were 0.77 ±0.59, 0.76 ±0.53, 0.70 ±0.47, 0.63 ±0.43,0.61 ±0.43, 0.62 ±0.42 log MAR, respectively, and showed significant improvement at 3, 6, 12mo(P =0.003, P =0.002,P =0.018, Wilcoxon signed-rank test). The mean CMT at baseline, 1, 2, 3, 6, and 12 mo was 312.41 ±66.38 μm,244.59 ±71.47 μm, 232.32 ±69.41 μm, 226.69 ±69.03 μm,228.62 ±37.07 μm, 227.59 ±51.01 μm respectively, and showed significant reduction(all P 【0.001, Wilcoxon signed-rank test). Polypoidal lesions resolved on ICGA in 3 eyes(11.1%) and a branching vascular network remained in all 24 eyes(88.9%). A total of 106 injections were given in the 12-month period, which equaled to a mean of 3.92(range, 3-6) times. Sixteen of the 27 treatedeyes had additional 1.56 ±0.91 injections. The others(11eyes) had just 3 consecutive injections.CONCLUSION: An initial loading dose of three monthly ranibizumab injections is a safe and effective method in treating PCV, with visual and anatomical improvement over one year follow-up.

Efficacy of intravitreal injection of ranibizumab in the treatment of macular edema secondary to non-ischemic branch retinal vein occlusion

Objective: To observe the efficacy of intravitreal injection of ranibizumab in the treatment of macular edema(ME) secondary to non-ischemic branch retinal vein occlusion (BRVO). Methods: The clinical data of 27 patients (27 eyes) with macular edema secondary to non-ischemic BRVO were diagnosed by ophthalmology in Chongqing University Center Hospital from May 2018 to April 2019, selected as the experimental group, and 20 cases (20 eyes) of normal people as the control group. For the experimental group, before and after treatment, 1wk, 1mo, 2mo, 3mo and 6mo were used to observe the uncorrected visual acuity(UCVA),best corrected visual acuity (BCVA), intraocular pressure (IOP), central retinal thickness (CRT) macular center volume (MCV) and EN FACE images. Subjects in the normal control group were examined by optical coherence tomography (OCT) for CRT and CMV at 1wk, 1mo, 2mo, 3mo and 6mo on the day of and after enrollment. Results: The mean age of patients in the experimental group was (67.37±8.63) years old and the times of Intravitreal injection was (3.26 ±0.59) times. The successful rate of treatment was 85.19%. There was no significant difference in IOP between pre-treatment and 1wk, 1mo, 2mo, 3mo and 6mo (P > 0.05). 1wk, 1mo, 2mo, 3mo and 6mo BCVA were significantly higher than those before treatment (P < 0.0001). The levels of CRT and CMV at 1wk, 1mo, 2mo, 3mo and 6mo after treatment were significantly lower than those before treatment (P <0.01). Compared with the normal control group, the CRT and CMV of the experimental group before and after treatment showed statistically significant differences in 1wk, 1mo, 2mo and 3mo (P <0.05). There was no statistically significant difference in 6mo CRT and CMV after treatment (P>0.05). EN FACE showed that 1wk, 1mo, 2mo, 3mo and 6mo macular thickness decreased gradually, retinal edema subsided, cystoid changes disappeared, and the interlamellar structure of the ellipsoid zone gradually recovered after intravitreal injection of ranibizumab. Conclusion: Intravitreal injection of ranibizumab in the treatment of non-ischemic BRVO secondary ME has significant efficacy, EN FACE is an effective means to assess the severity, treatment and prognosis of patients.

Immediate intraocular pressure rise after intravitreal injection of ranibizumab and two doses of triamcinolone acetonide

AIM: To evaluate prospectively immediate intraocular pressure (IOP) changes after the intravitreal injection of ranibizumab, 2 and 4mg triamcinolone acetonide. METHODS: Patients who underwent intravitreal injection of 0.1mL (4mg) triamcinolone acetonide (TA, Group T4), 0.05mL (2mg) TA (Group T2) and 0.05mL (0.5mg) ranibizumab (Group R) comprised the study population. Overall, 229 eyes of 205 patients were injected. Fifty-four eyes (23.6%) were in Group T4, 69 eyes (30.1%) in Group T2 and 106 eyes (46.3%) in Group R. If IOP was less than 26mmHg immediately after the injection no further measurement was performed. If IOP was ≥26mmHg, IOP was remeasured till the reading was below 26mmHg at 5, 15 and 30 minutes. RESULTS: Immediately after the injection, the IOP of 28 eyes (51.9%) in Group T4, 22 eyes (31.9%) in Group T2 and 51 eyes (48.1%) in Group R were over 25mmHg. At 30 minutes, IOP of one eye (1.9%) in group T4, two eyes (2.9%) in group T2 and two eyes (1.9 %) in Group R were over 25mmHg. Immediate post-injection IOP was significantly higher in Group T4 and Group R when compared to Group T2 (P <0.001 and P <0.001, respectively). IOP was significantly higher in eyes without vitreous reflux when compared to those with vitreous reflux in all groups (P <0.001). CONCLUSION: IOP may remarkably increase immediately after the intravitreal injection of 2 or 4mg triamcinolone acetonide, and 0.5mg ranibizumab. Absence of vitreous reflux is the most important predicting factor for immediate IOP rise after the injection.

Retinal Functional Changes Measured by Microperimetry after Intravitreal Ranibizumab Injection and Sulfotanshinone Sodium Injection for Macular Edema Secondary to Retinal Vein Occlusion

Objectives: To study the visual field changes after intravitreal ranibizumab (IVR) injection and sulfotanshinone sodium (SS) injection for macular edema (ME) secondary to retinal vein occlusion (RVO), and discuss the value of microperimetry as a routine diagnostic test in the follow-up of RVO patients. Methods: This was a retrospective, interventional, case-series study. Twelve eyes of 12 RVO patients, including 6 eyes with central RVO (CRVO) and 6 eyes with branch RVO (BRVO) were included. The eyes were treated with IVR (0.5 mg) injections and SS injections (20 mg per day, one week consecutively in one month). The outcomes measured included best corrected visual acuity (BCVA), central retinal thickness (CRT), mean defect (MD), pattern standard deviation (PSD), macular light sensitivity of the central 16 points in CRVO group and the central 8 points in BRVO group before and after the treatment. Statistical analyses were then performed on the main outcome measures. Results: An improvement of BCVA was found in all patients after treatment with significant difference (t = 7.74, p p p p > 0.05). All RVO patients had their macular light sensitivity of the involved part improved significantly (t = 5.03, p p p < 0.01). The Pearson’s correlation was calculated among BCVA, MD, macular light sensitivity and CRT. No obvious significance was found between CRT and BCVA outcomes, whereas MD and mean macular light sensitivity outcomes were closely related to BCVA results in the BRVO group and the latter showed a more intimate correlation. No similar correlation was found in RVO and CRVO group. Conclusion: IVR injection and SS injection together could effectively improve the therapeutic effect in RVO patients with ME. Microperimetry could be used as a routine diagnostic test and a possible valuable tool in the follow-up of patients with RVO, especially in BRVO.

Intravitreal Ranibizumab Combined with Sulfotanshinone Sodium Injection in Treating Type II Optic Disc Vasculitis

Objectives: To present the effect of intravitreal ranibizumab (IVR) therapy combined with sulfotanshinone sodium (SS) injection in a patient suffering from type II optic disc vasculitis (ODV). Methods: A 26-year-old female patient was diagnosed with type II ODV with macular edema (ME). The information was obtained by complete medical and ophthalmic history taking and a detailed ophthalmic examination at the initial and follow-up visits. Functional and morphological outcomes at baseline, 1 week and 1 month following IVR+SS injections, are presented. Results: Best-corrected visual acuity (BCVA) improved from 78 letters (ETDRS) at baseline to 90 letters at 1-week follow-up and maintained stable through 1-month follow-up. Central retinal thickness (CRT) measured by optical coherence tomography (OCT) decreased from 465 μm at baseline to 240 μm at 1-week follow-up and to 226 μm at 1-month follow-up. Mean deviation (MD) measured by perimetry increased from ?5.17 dB to ?4.59 dB and to ?4.29 dB, respectively. Fluorescein angiography (FFA) showed that the initial macular edema at baseline disappeared while the arm-retina circulation time (ART) was also greatly shortened when compared to the baseline. Electroretinogram (ERG) measured at 1-month follow-up demonstrated an overall improvement of the retinal function after the injection. No ocular or systemic side effects were detected. Conclusions: IVR+SS injection may lead to resolution of the associated ME and improve the retina morphologically as well as functionally. To our knowledge, this is the first case of a type II ODV benefiting from treatment with IVR+SS injection. The observed results warrant further investigation.

Short-term fluctuation of intraocular pressure and influencing factors following intravitreal injection in patients with retinal vascular diseases

AIM:To investigate the patterns of short-term intraocular pressure(IOP)fluctuations and identify the contributing factors following intravitreal injection in patients with retinal vascular diseases.METHODS:Totally 81 patients were enrolled in this case control study.Eyes were categorized into 7 groups,including age-related macular degeneration(AMD),polypoidal choroidal vasculopathy(PCV),idiopathic choroidal neovascularization(CNV),proliferative diabetic retinopathy(PDR),diabetic macular edema(DME),macular edema secondary to branch(BVOME)and central(CVOME)retinal vein occlusion.IOP was measured in all patients using rebound tonometer at 7 preset time points perioperatively.Additionally,based on the administered medication,the eyes were classified into three treatment groups,including dexamethasone intravitreal implant(IVO),intravitreal conbercept(IVC),and intravitreal ranibizumab(IVR).To compare IOP values at various time points across groups,we employed one-way ANOVA,independent sample t-test or χ^(2) test and multivariate logistic regression analysis.RESULTS:Peak IOP values across all groups were observed at 40s,and 5min after intravitreal injection.Statistical differences in IOP were detected at the 5min among the 7 indication groups(F=2.50,P=0.029).When examing the impact of medications,the IVO group exhibited lower average IOP values at both 40s and 5min compared to the IVC and IVR groups(P<0.001;P=0.007).The IOP values at 40s and 5min were significantly higher in BVOME and CVOME group compared to non-retinal vein occlusionsecondary macular edema(RVOME)group(P<0.001).Multivariate logistic regression analysis further confirmed that IOP measurement at 40s was significantly higher in CVOME group than in non-RVOME group(OR=1.64,95%CI:1.09-2.47;P=0.018).CONCLUSION:Needle size plays a crucial role in the transient changes of IOP following intravitreal injection.Before administering intravitreal injection to patients with central retinal vein occlusion,it is essential to exclude any underlysing causes of increased IOP.

Impact of switching from ranibizumab to aflibercept on the number of intravitreous injection and follow up visit in wet AMD:results of real life ELU study

●AIM:To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection(IVI)with the same efficacy.●METHODS:ELU(or"elected"in French)study is a retrospective study conducted in real life in patients presenting suboptimal response after ranibizumab IVI(phase 1)and secondary switched to aflibercept(phase 2).The number of follow up visits and IVI were compared in both phases.Visual acuity(VA)evolution and"switching"reasons were secondary analyzed.●RESULTS:We retrospectively included data of 33 patients(38 eyes)with age-related macular degeneration(AMD;mean age:77±7.7 y).The number of monthly follow up visits[median(Q1;Q3)]:was significantly lower with aflibercept(phase 2),respectively 1.0(0.81;1.49)visits in phase 1,versus 0.79(0.67;0.86)visits in phase 2.The median number of monthly IVI also significantly decreased in phase 2,respectively 0.67(0.55;0.90)IVI in phase 1,versus 0.55(0.45;0.67)IVI in phase 2.The mean VA evolution(VA final-VA initial)was similar in both phases,(P>0.05).Whatever the reason for"switching"(loss of efficacy,tachyphylaxis,tolerance problems),there was no incidence on VA evolution over the time.●CONCLUSION:Our results show that switching from ranibizumab to aflibercept in"suboptimal"patients significantly reduce the number of follow up visits and IVI,with a comparable efficacy.This decrease in visit number could improve patients’quality of life and reduce surgical risk by reducing the number of injections.

Efficacy evaluation of intravitreal ranibizumab therapy for three types of retinopathy of prematurity

AIM:To evaluate efficacy of intravitreal ranibizumab(IVR)therapy for aggressive posterior retinopathy of prematurity(ROP),threshold ROP disease and type 1 pre-threshold ROP.METHODS:A retrospective analysis was performed on 40 patients(76 eyes)who had IVR as the primary treatment for ROP from April 2017 to January 2018.According to disease pathogenic features,the 76 eyes were divided into three groups:aggressive posterior ROP(AP-ROP)group(16 eyes),threshold ROP group(28 eyes)and type 1 pre-threshold ROP group(32 eyes).The characteristics of patients and lesions situation before the first intravitreal injection,and posttreatment fundus outcomes determined by wide-angle Ret Cam fundus imaging were recorded.RESULTS:The birth weight and postmenstrual age of first IVR treatment in AP-ROP,threshold ROP,and type 1 pre-threshold ROP groups were significant difference(1087.50±246.78,1103.75±168.30,1257.03±210.82 g,P=0.005;34.50±1.46,36.89±2.97,36.50±2.36 wk,P=0.008),while the gestational age was not difference(28.00±2.00,28.54±1.90,28.59±1.43 wk,P=0.510).The retina hemorrhage ratio(with/without:14/2,8/20,5/27),iris neovascularization or vascular engorgement ratio(with/without:12/4,11/17,6/26),and the zone I(inside/outside:16/0,2/26,5/27)in AP-ROP,threshold ROP,and type 1 pre-threshold ROP group were difference significantly(all P<0.05).The regression rates were 37.5%,92.86%,and 100%,and the recurrence rates were 62.5%,7.14%,and 0 in AP-ROP,threshold ROP,and type 1 pre-threshold ROP group,respectively(both P<0.05).The recurrence eyes were cured by secondary IVR or retinal laser photocoagulation.CONCLUSION:IVR is an effective treatment for all types of ROP.The regression of AP-ROP is significantly lower than type 1 pre-threshold and threshold disease.Birth weight,retinal hemorrhage,iris neovascularization or vascular engorgement and lesions located in zone I may be associated with AP-ROP recurrence and retreatment,which should be noted in follow-up.

The Effect of Intraocular Pressure Lowering Medications on the Pressure Spike Associated with Intravitreal Injection

Aim: This study investigates whether the post intravitreal injection intraocular pressure (IOP) spike is modifiable with the use of prophylactic apraclonidine and dorzolomide. Methods: The study design was a prospective, randomised controlled trial. 80 eyes undergoing intravitreal injection of anti-VEGF agent were studied. A control group (n = 42) received no IOP lowering drops, and a study group (n = 38) received guttae apraclonidine and dorzolamide 30 to 40 minutes before the intravitreal injection. IOP measurements were taken in both groups using the Perkins tonometer at baseline, immediately before and after the injection, 5 minutes post-injection, and 15 minutes post-injection. Results: Mean IOP immediately post injection in the study group was 26.71 mmHg, and in the control group was 32.73. The main outcome measure was the area under the curve (AUC)—reflecting the trend of IOP post injection. The AUC was lower in the study group compared to the control group (Mann-Whitney U test, p = 0.046). Conclusions: The use of prophylactic apraclonidine and dorzolamide is effective in modifying the post-injection IOP spike. IOP lowering prophylaxis may be considered in patients with a high baseline IOP.

Intravitreally injected ranibizumab versus photodynamic therapy for CNV secondary to choroidal osteoma:a 7-year follow-up case report

Dear Editor,We present a case of bilateral choroidal neovascularization(CNV)secondary to choroidal osteoma involving the macula and investigate the effect of intravitreal injection of ranibizumab and photodynamic therapy(PDT)in a sevenyear follow-up.Informed consent for patient information and images to be published was obtained from the patient included in the study based on the Declaration of Helsinki,which was approved by the Ethics Committee of Southwest Hospital.

Retinal injury following intravitreal injection of a dexamethasone implant in a vitrectomized eye

Lee SM, Jung JW, Park SW, Lee JE, Byon IS. Retinal injury following intravitreal injection of a dexamethasone implant in a vitrectomized eye. Int J Ophthalmo12017; 10（6）： 1019-1020

Comment on bilateral same-session intravitreal injections

【正】Dear Editor,We have read the article by Abu-Yahgi et al[1]with great interest.The authors share their experience with bilateral same-session intravitreal injection of anti-vascular endothelial growth factors(anti-VEGF).They report a single case of endophthalmitis in a series of 342 injections of 74patients and compare their results with their 3634 cases of unilateral injections with 2 cases of endophthalmitis[1].There are some issues related with the article that may benefit from

Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor(VEGF)protein and VEGF mRNA in the retina of diabetic rats.·METHODS:Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups,each containing 24animals and 48 eyes.Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline,while in groups B and C were injected with 3μL(75μg)of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles(containing 75μg of bevacizumab),respectively.Immunohistochemistry was used to assess retinal angiogenesis,real-time PCR assay was used to analyze the expression of VEGF mRNA,and light microscopy was used to evaluate the morphology of retinal capillaries.·RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A(P】0.05),while the VEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection(P【0.05).Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection(P【0.05)in group B,and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection(P【0.05)in group C.Using multiple comparisons among group A,group B,and group C,the VEGF expression before injection was higher than at 1,4 and 8 weeks after injection(P【0.05).The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection,andalso higher 1 week after injection compared with 4 weeks after injection(P【0.05).No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.·CONCLUSION:The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of bevacizumab inhibits VEGF expression in retina,and bevacizumabchitosan nanoparticles have a longer duration of action.

Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

· AIM: To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly(L-lactic-co-glycolic acid)(PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.·METHODS: Bevacizumab was encapsulated into PLGA microsphere via the solid- in- oil- in- hydrophilic oil(S/O/h O) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at day 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.·RESULTS: The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than thatof bevacizumab solution. The T1/2of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2of intravitreal injection of soluble bevacizumab is 3.91 d in vitreous and4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes(P 【0.05). The AUC0-tof the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly.The immunofluorescence staining of PLGA-encapsulated bevacizumab(b-PLGA) in rabbit eye tissues was still observed up to 42 d. It was longer than that of the soluble form.· CONCLUSION: The result of this study shows the beneficial effects of PLGA in prolonging the residency of bevacizumab in the vitreous. And the drug delivery system may have potential as a treatment modality for related disease.

Iatrogenic crystalline lens injury during intravitreal injection of triamcinolone acetonide: A report of two cases

BACKGROUND Intravitreal injection has become an efficient approach for delivering drugs at therapeutic levels to the posterior segment in retinal diseases.However,the increased frequency and number of intravitreal injections have raised concerns about their side effects.As manipulation during surgery is relatively simple,details of the procedure are easily overlooked.Iatrogenic crystalline lens injury is a rare complication caused by improper manipulation during surgical procedures.We report two cases of crystalline lens injury during intravitreal injection of triamcinolone acetonide(TA)with the hope of providing an insight into this treatment.CASE SUMMARY Case 1 was a 62-year-old woman with macular edema caused by central retinal vein occlusion in her right eye,and Case 2 was a 65-year-old man with macular edema caused by branch retinal vein occlusion in his right eye.In view of the patients’condition and economic constraints,an intravitreal injection of TA was administered.Due to inappropriate manipulation during surgery,the lens was injured.The site of lens injury and clinical manifestations were different in the two cases.Symptomatic treatment and continuous follow-up were carried out.The therapeutic effect following phacoemulsification of the cataract was satisfactory.CONCLUSION Well-defined surgical incision under proper anesthesia,sufficient patient information and proficient anatomical skills of the physician are mandatory to prevent this rare adverse event.Careful and meticulous phacoemulsification of the cataract is suggested.

Effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections

AIMTo evaluate the effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections.

Study of the Influence of Angiostatin Intravitreal Injection on Vascular Leakage in Retina and Iris of the Experimental Diabetic Rats

Purpose: To examine the effect of an intravitreal injection of angiostatin on vascular leakage in retina and iris of the diabetes and study its possible mechanism. Methods: Experimental diabetes was induced in 24 rats by an intravenous injection of streptozotocin (STZ) during 48 adult rats. Three groups were randomization distributed of them. There were 8 of both normal and diabetic rats in each group. STZ-diabetic rats and age-matched normal rats received an intravitreal injection of 5 μl of sterile PBS (Phosphate Buffered Saline) into the right eye, and the left eye was non-injected in the group A; Angiostatin was injected into the vitreous of the right eye (7.5 μg / 5 μl / eye), and the left eye received the same volume of sterile PBS as the control in the group B and C. The vascular permeability of retina and iris was measured using the Evans blue method at 2 days following the injection in the group A and B. Expression of VEGF in retina was evaluated using western blot analysis 24 hours following the injection in the group C. Results: Diabetic rats showed significant increases of vascular permeability in the retina ( P < 0.01) and iris ( P < 0.05). Angiostatin-injected eyes showed significant decreases in vascular permeability in the retina ( P < 0.01) and iris ( P < 0.05) comparing with the PBS-injected eyes in STZ-diabetic rats. In contrast, intravitreal injection of the same dose of angiostatin into the age-matched normal rats did not result in any significant reduction in vascular permeability in the retina and iris, when compared with the contralateral eye with PBS injection ( P > 0.05). Angiostatin injection significantly reduced VEGF level in the retinas of STZ-diabetic rats but did not affect retinal VEGF level in normal rats. Conclusions: Angiostatin significantly reduce pathological vascular permeability in the retina and iris of STZ-diabetic rats but not in normal rats. Angiostatin down-regulates VEGF expression and thus, blocks the major cause of vascular leakage in the diabetic retina. Therefore, angiostatin may have a therapeutic potential in the treatment of diabetic macular edema, cystoid macular edema, uvietis and other diseases with vascular leakage.

Effects of perioperative managements on ocular surface microbiota in intravitreal injection patients

AIM:To investigate the effects of on ocular surface microbiota in patients who received intravitreal injections.METHODS:Samples of ocular surface microbiota were obtained from 41 eyes of 41 patients who visited the Department of Ophthalmology.Patients were separated for three groups.Group A did not receive perioperative managements or intravitreal injection.Group B1 received only once and B2 received more than twice.In operating room,the samples were collected on the ocular surface.Operating taxonomic units(OTUs) clustering and alpha/beta diversity analysis was performed.The microbial 16S rRNA from samples were analyzed using the Hi Seq 2500 platform.RESULTS:Alpha diversity did not differ in each group,and beta diversity differed in the B2 group.Beta diversity showed a significant difference between Group A and B2(P=0.048).With the perioperative managements before intravitreal injection,the composition and relative abundance were altered.Top 10 microbiota on phylum and genus level,and then microbiota notably changed at genus level were listed.Gram-negative bacteria were varied more.Furthermore,Proteus was not found in Groups A and B1,but it was appeared after the patients received perioperative management and intravitreal injections in Group B2.CONCLUSION:With the perioperative managements,the balance of microbiota on the ocular surface is destroyed,and relative composition and abundance of microbiota on the ocular surface is obviously altered.The clinical doctors should pay more attention on the consequence of perioperative managements before intravitreal injection.

The Role of Prophylactic Antibiotic Use in Prevention of Endophthalmitis Following Intravitreal Injection of Anti-Vascular Endothelial Growth Factor Agents: A Meta-Analysis

Purpose: To determine the role of prophylactic antibiotic use in preventing endophthalmitis following intravitreal injections of Anti-Vascular Endothelial Growth Factor Agents (anti-VEGF).Methods: A meta-analysis was conducted for studies reporting the rates of endophthalmitis following injection of anti-vascular endothelial growth factor agents for a variety of disorders. Inclusion criteria included reporting how many patients were given post-injection antibiotic drops, and how many patients were diagnosed with endophthalmitis (both with and without antibiotic drops). Results: The reported rate of endophthalmitis following intravitreal anti-VEGF agents has varied significantly based on the study, with a range between 0.009% to 0.87%. In our meta-analysis, the rate of endophthalmitis in patients receiving post-injection antibiotics was found to be 0.081%, compared to 0.072% for patients who did not receive antibiotics. This difference was not found to be statistically significant. Conclusion: Although the rate of endophthalmitis is extremely low following intravitreal anti-VEGF injections, the controversy regarding the best prevention of this dreaded complication continues. According to our meta-analysis, the answer does not seem to lie in post-injection antibiotic use.

The ocular toxicity and pharmacokinetics of simvastatin following intravitreal injection in mice

AIM：To investigate the retinal toxicity and pharmacokinetics of simvastatin intravitreally injected into mice.METHODS：Forty-eight 6-8-week-old C57BL/6J mice were used in this study.Simvastatin was intravitreally injected into the right eye of each mouse;the left eye was injected with vehicle and was used as a control.Bilateral dark-adapted electroretinography（ERG）was performed 1 and 7d following injection.Histology was examined using a combination of light,fluorescence and electron microscopy.Highperformance liquid chromatography（HPLC）was used to determine the decay in the retinal simvastatin concentration.RESULTS：ERG revealed no significant changes in the simvastatin-injected eyes compared to control.Histologic studies showed normal retinal morphology in eyes injected with simvastatin up to a final vitreal concentration of 200μmol/L.No significant changes in the number of photoreceptors,bipolar cells or ganglion cells were found.The retinal simvastatin concentration decayed exponentially,with a half-life of 1.92-2.41h.CONCLUSION：Intravitreal injection of up to 200μmol/L simvastatin produced no signs of adverse effects in the mouse retina.Simvastatin reaches the retina shortly after intravitreal injectionand has a short half-life.