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.

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.

Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes

●AIM:To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections(IVAIs)on immediate intraocular pressure(IOP)increase and vitreous reflux(VR)rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate.●METHODS:This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion,35 patients with diabetic macular edema,69 patients with neovascular age-related macular degeneration(nAMD),and 12 patients with myopic choroidal neovascularization,which underwent first-time IVAI.The correlation of immediate IOP increase and VR rates with the four background diseases was investigated.Moreover,the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated.Further,54 patients with nAMD were treated with IVAI>10 times(multiple IVAIs).Moreover,the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined.●RESULTS:The immediate IOP increase(P=0.16)and VR rates(P=0.50)were almost similar among the four background diseases.The immediate postinjection IOP and age,VR rate and age,immediate postinjection IOP and axial length,or VR rate and axial length were not correlated in the four background diseases.The immediate IOP increase(P=0.66)and VR rates(P=0.28)did not significantly differ between first-time and multiple IVAIs in nAMD.●CONCLUSION:Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate.Further,age and axial length have no correlation on immediate IOP increase and VR rate.

Intravitreal injection practice patterns among Chinese ophthalmologists

AIM:To describe the practice patterns of intravitreal injections(IVIs)among ophthalmologists in China.METHODS:This was a cross-sectional online survey.Ophthalmologists who had performed accumulated more than 100 injections were contacted by the Brightness Center,a hospital-based national network,to complete an anonymous,24-question,internet-based survey.They were surveyed on practices in injection techniques,pre-,and post-injections procedures.RESULTS:A total of 333 ophthalmologists from 28 provinces/municipalities/autonomous regions responded to the survey(50.68%response rate).The 91.29%of the respondents evaluated systemic risk factors by medical history,electrocardiogram(ECG)and blood test.All the respondents used pre-injection prophylactic antibiotics.Most checked intraocular pressure(IOP,99.1%)and blood pressure(96.1%)before injections.A majority of the respondents performed injections in the operating room(98.8%),wore masks(99.7%),gloves(99.4%)and sterile surgical clothing(96.1%),performed topical anesthetics(97.9%),and applied povidone-iodine(95.8%)pre-injection.The 61.26%of the respondents dilated pupil.About half of the respondents(51.05%)performed bilateral injections in the same setting.Superior temporal quadrant(40.54%)was the most frequent site of injection.Around three quarters used 30-gauge needles.Most respondents(97.9%)measured the site of injection from limbus.More than half(53.45%)performed conjunctiva displacement prior to injection.The 32.43%of the respondents checked IOP post-injection and 87.99%physicians checked hand motion(HM)or counting fingers(CF)after injection,while 36.94%observed optic nerve perfusion.All participants used topical antibiotics post-injections.Most physicians(91.89%)reviewed patients on the following day.CONCLUSION:This study provides a description of the real-world practice patterns in IVIs in China and offers critical information regarding education and training of ophthalmologists and amendment of local society guidelines.

Iridociliary Body Metastasis of Atypical Carcinoid: Case Management with Intravitreal Anti-Vascular Endothelial Growth Factor Injections

We report a rare case involving a 52-year-old female diagnosed with an atypical bronchial carcinoid tumor with metastases to the mediastinum, hilar lymph nodes, breast, and pancreas. In additional, the patient had metastases to the iris and ciliary body, resulting in progressive vision loss in her left eye. Treatment was successful by intravitreal injections of anti-vascular endothelial growth factor.

Combination of cataract surgery with intravitreal injection of dexamethasone intravitreal implant(Ozurdex)for uveitis-induced cataract

AIM:To evaluate the long-term results of patients with chronic uveitis-induced cataract by phacoemulsification with IOL implantation and intravitreal injection of dexamethasone(DEX)intravitreal implant(Ozurdex).METHODS:The study included 32 eyes of 26 patients treated with DEX implant due to chronic uveitis-induced cataract and followed up for at least a year.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),anterior chamber reaction,central macular thickness(CMT),intraoperative and postoperative complications and uveitis recurrence were analyzed retrospectively.RESULTS:A successful surgery was performed in all patients.The average follow-up period was 12mo.The female/male ratio was 13/13.Mean age was 45.65±3.83y(range 26 to 65y).Etiologically,rheumatic arthritis occurred in 6 patients(18.75%),ankylosing spondylitis in 4(12.50%),HLA-B27 associated uveitis in 3(9.38%),Vogt-KoyanagiHarada-associated uveitis in 4(12.50%),Behcet’s disease in 2(6.25%),and 7(21.88%)suffered from unknown diseases.All 32 eyes had varying degrees of improvement at 12mo after surgery,with 2 eyes showing BCVA of 0.1 or below(6.25%),6 having 0.1-0.5(18.75%),18 of 0.5-1.0(56.25%),and 6 of 1.0 or above(18.75%).No cases with increased IOP were observed.The values of mean CMT was increased at day 1,decreased at 1,3mo after surgery and increased at 6,12mo after surgery.No severe uveitis reactions,such as fibrinous exudates in the anterior chamber and exudative membrane formation on the anterior surface of the IOL,were observed after surgery.CONCLUSION:The present studies show that intravitreal injection of Ozudex during cataract operation can provide a new option for the clinical treatment of uveitis-induced cataract.

Endophthalmitis in silicone oil-filled eye: A case report

BACKGROUND Endophthalmitis occurring in silicone oil-filled eyes is a very rare occurrence,with reported incidence rates ranging between 0.07%and 0.039%.Traditional methods of management of infectious endophthalmitis include the removal of silicone oil,washout of the vitreous cavity,administration of intravitreal antibiotics,and reinjection of silicone oil.CASE SUMMARY Herein,we report the case of a 39-year-old man with unilateral endophthalmitis after pars plana vitrectomy and silicone oil tamponade.Intravitreal injections of full-dose antibiotics and anterior chamber washout were used to treat the patient.No signs of retinal toxicity were observed during the follow-up period.CONCLUSION Intravitreal full-dose antibiotic injections and anterior chamber washout are promising alternatives to traditional therapies for endophthalmitis in silicone oilfilled eyes.

Pharmacological adjuvants for diabetic vitrectomy surgery

Diabetic vitrectomy is a highly intricate surgical procedure performed during the advanced stages of diabetic retinopathy(DR).It is used to treat conditions such as tractional or combined retinal detachment,vitreous hemorrhage,and subhyaloid hemorrhage,which are all severe manifestations of proliferative DR.The results of the surgery are uncertain and variable.Vitreoretinal surgery has made significant progress since the early stages of vitrectomy.In the past ten years,advancements in intravitreal pharmacotherapy have emerged,offering new possibilities to improve the surgical results for our patients.Within the realm of medical terminology,an"adjunct"refers to a pharmaceutical or substance employed to aid or expedite the primary therapeutic intervention for a particular ailment.Their introduction has broadened the range of therapeutic choices that are accessible prior to,during,and following surgical procedures.This review article will specifically analyze the pharmacological adjuncts used in diabetic vitrectomy surgery,with a focus on their role in facilitating or aiding specific steps of the procedure.The implementation of this system of categorization offers benefits to the surgeon by allowing them to foresee potential difficulties that may occur during the surgical procedure and to choose the appropriate pharmacological agent to effectively tackle these challenges,thus enhancing surgical success rates.

The Incidence of Endophthalmitis Cases in an Island Nation

Endophthalmitis is a severe ocular infection which can have sight threatening complications and should be treated urgently. Malta is an archipelago in the middle of the Mediterranean sea, with one main hospital (Mater Dei Hospital), where all emergency ophthalmic cases are referred during the years audited. This allowed the authors to review all the cases of endophthalmitis which presented to Mater Dei Hospital from 2009 to 2020 and to be able to reliably compare incidence of local endophthalmitis cases with worldwide quoted incidence rates. All theatre logbooks documenting procedures locally from 2009 to 2020 were reviewed and patients undergoing intravitreal tap and antibiotics injections were included in this audit. This was based on the assumption that all endophthalmitis cases which presented underwent these procedures. Data was analyzed and the average incidence of endophthalmitis cases noted and compared with international numbers. The local numbers are higher than the accepted average, taking into consideration sources of error during data collection for this audit. The authors suggest that a local standard operating procedure in terms of response of suspected endophthalmitis is needed as well as a register for local endophthalmitis cases.

Diabetic retinopathy:A review on its pathophysiology and novel treatment modalities

Diabetes mellitus(DM)is a chronic metabolic non-communicable disease with the ability to cause serious microvascular and macrovascular complications throughout the body,including in the eye.Diabetic retinopathy(DR),present in onethird of patients with diabetes,is a vision-threatening complication caused by uncontrolled diabetes,which greatly affects the retinal blood vessels and the lightsensitive inner retina,eventually leading to blindness.Several epidemiological studies elucidate that DR can vary by age of onset,duration,types of diabetes,and ethnicity.Recent studies show that the pathogenesis of diabetic retinopathy has spread its roots beyond merely being the result of hyperglycemia.The complexity of its etiopathology and diagnosis makes therapeutic intervention challenging.This review throws light on the pathological processes behind DR,the cascade of events that follow it,as well as the available and emerging treatment options.

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.

Intraocular pressure elevation after intravitreal triamcinolone acetonide injection: a Meta-analysis

AIM：To report on intraocular pressure（IOP）after intravitreal injections of triamcinolone acetonide.·M ETHODS：Systematic literature review of studies that investigated the effects of an injection of triamcinolone Intravitreal triamcinolone acetonide on IOP was conducted according to the Cochrane Collaboration methodology and the reported effects have been analyzed with Meta-analysis.·RESULTS：We found that the IOP follows an inverted-U shape pattern over time starting with an average value of14.81±1.22 mm Hg before the injection,rising to a maximum of 19.48±2.15 mm Hg after one month of injection and falling down to 16.16±1.92 mm Hg after6mo.Moreover,country of study,age,previous history of glaucoma and gender compositions matter for crossstudy were different in reported IOP changes.·CONCLUSION：Our findings may be helpful in determining pressure elevation risk of intravitreal triamcinolone acetonide therapy as well as comparing it with those of more recent therapies such as the antivascular endothelial growth factor agents.

Intravitreal injection of resveratrol inhibits laser-induced murine choroidal neovascularization

AIM:To determine the effects of intravitreal resveratrol(RSV)on murine laser-induced choroidal neovascularization(CNV).METHODS:The toxicity of RSV to choroidal endothelial cell(CEC)was measured using thiazolyl blue tetrazolium bromide(M一)assay.Effects of RSV on choroidal endothelial cell(CEC)migration were evaluated with a modified Boyden chamber assay,while tube formation was evaluated in a 2-D gel assay.CNV was induced by laser photocoagulation in mice.The effects of intravitreal injection of RSV on CNV development were evaluated by fluorescein angiography(FA),confocal analysis of isolectin B4 labeled choroidal flat mounts,and histologic examination of CNV membranes.Immunostaining was used to analyze the expression and phosphorylation of vascular endothelial growth factor receptor 2(VEGFR2).RESULTS:No significant cell toxicity was observed in CEC if the concentration of RSV was less than 200 pmol/L(P>0.05).RSV inhibited vascular endothelial growth factor(VEGF)-induced CEC migration(P<0.05)and tube formation(P<0.05)invitro.Furthermore,intravitrealinjectionof RSV significantly inhibited laser induced CNV formation in mice.The FA leakage,CNV volume and CNV area analysis revealed that there were 41%,45%,and 58%reduction in RSV-treated eyes(1.691±0.1032,178163±78623μm^3 and 6508±619.0μm^2,respectively)compared with those in control(2.724±0.08447,379676±98382μm3and16576±2646μm^2,respectively;P<0.05).Phospho-VEGFR2expression was much weaker in the sections of CNV lesions in RSV injected mice compared with that in control(P<0.05).CONCLUSION:Intravitreal injection of RSV exerts an inhibitory effect on CNV,which may through suppressing endothelial cell migration,tube formation and VEGFR2 phosphorylation.

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.

Optimal timing of preoperative intravitreal anti-VEGF injection for proliferative diabetic retinopathy patients

AIM: To analyze concentrations of vascular endothelial growth factor(VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy(PDR) patients pretreated with intravitreal anti-VEGF injections(IVI) at different time periods prior to pars plana vitrectomy(PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative IVI.METHODS: The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDRrelated complications(PDR group) and 21 eyes with nondiabetic ocular disease(control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3 d after IVI(3-day group);5 d after IVI(5-day group);7 or more days after IVI(≥7-day group);and no IVI. Vitreous fluid samples(0.5-1.0 m L) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor(b FGF), periostin(PN), interleukin(IL)-6, IL-8, and tumor necrosis factor(TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression analysis.RESULTS: PDR eyes without IVI had significantly higher VEGF, b FGF, PN, and IL-6 concentrations than nondiabetic eyes(all P<0.05), and had a significantly higher concentration of VEGF(P<0.05) and a significantly lower concentration of IL-8(P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, b FGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups(all P<0.05);meanwhile there was no significant difference in TNF-α among groups(P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of b FGF and PN. The degree of vitreoretinal fibrosis was significantly higher in the ≥7-day group compared to the 3-day(P=0.015) and 5-day group(P=0.039), and vitreoretinal fibrosis correlated significantly with concentrations of b FGF, PN, IL-6, and IL-8(all P<0.05). Univariate ordinal logistic regression analysis showed that b FGF was an independent risk factor for the severity of vitreoretinal fibrosis in PDR patients pre-treated with IVI.CONCLUSION: The vitreous concentrations of VEGF, b FGF, PN, IL-6, and IL-8 change after pretreatment with IVI before PPV in PDR patients. The degree of vitreoretinal fibrosis is higher in patients with a longer time between IVI treatment and PPV, which may be related to the angiofibrosis switch. The results suggest that PPV should be performed 5 d after IVI administration in PDR patients.

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.

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.

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 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.

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.