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.

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.

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.

Intravitreal conbercept injection for neovascular agerelated macular degeneration

AIM: To evaluate the efficacy and safety of intravitreal injection of conbercept in patients with neovascular agerelated macular degeneration(AMD). METHODS: Retrospective review of 66 eyes of 63 patients with neovascular AMD. All patients received 0.5 mg intravitreal injections of conbercept monthly for 3 consecutive months, and then pro re nata treatment was performed. The changes of best-corrected visual acuity(BCVA) and central macular thickness(CMT) were observed before and after treatments. Minimum follow-up time was 12 mo. SPSS 22.0 statistical software was used for statistical analysis.

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.

Effect of individualized therapy for AIDS patients with cytomegalovirus retinitis in intravitreal ganciclovir injections

The effect of intravitreal ganciclovir injection combined with intravenous infusion on acquired immune deficiency syndrome(AIDS) patients with cytomegalovirus retinitis(CMVR) was investigated. A total of 32 eyes in 23 AIDS patients diagnosed as CMVR from 2017 to 2018 were included in the retrospective study. All patients underwent induction therapy by using intravenous drip of the anticytomegalovirus(CMV) agent ganciclovir(5 mg/kg q12 h) combined with intravitreal ganciclovir injection(3 mg/time, 2 times/wk). The visual acuity, fundus photographs, lesion location, and number of intravitreal injections were observed preoperatively and postoperatively. Totally 14 eyes were cured during induction therapy. The number of injections [4.13(2 to 6)] in CMVR patients with peripherally fundus lesions were significantly lower than those with central lesions (4.89(2 to 6))The individualized therapy of intravitreal ganciclovir injections for AIDS patients with CMVR can effectively reduce the numbers of intravitreal injections.

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.

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.

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.

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.

Posterior vitreous detachment rate following intravitreal dexamethasone injection

AIM: To determine whether intravitreal dexamethasone(DEX) implant induces posterior vitreous detachment or not. METHODS: We retrospectively reviewed 810 eyes of 405 patients who underwent intravitreal DEX implantation due to macular edema caused by diabetic and retinal venous occlusion in our clinic. The eyes having no injection were determined as the control group. The examination findings of the patients before the injection and 3 mo after the injection and optical coherence tomography(OCT) images were scanned. The pre-injection OCT findings and OCT findings of the patients having no posterior vitreous detachment(PVD) and determined to have partial PVD were compared. RESULTS: The separation in vitreoretinal adhesion and total PVD development of DEX-injected 56/208(26.9%) eyes were statistically greater in comparison with the 12/129(9.3%) eyes that had not been injected(P=0.001). PVD development was observed more in the patients that were younger, had larger macula thickness and lower visual acuity. CONCLUSION: It can be stated that intravitreal DEX implant induces PVD development. Prospective, controlled studies are required in order to determine prognosis of vitreoretinal disease in PVD-developed patients and in non-PVD-developed patients.

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.

Choroidal structural changes determined by the binarization method after intravitreal aflibercept treatment in neovascular age-related macular degeneration

AIM:To assess the choroidal structural alterations after intravitreal injection of aflibercept in neovascular agerelated macular degeneration(n AMD).METHODS:Fifty eyes with treatment-naive n AMD were evaluated at baseline,3^(rd),and 12^(th) month.Fifty eyes of 50 healthy subjects were also included as controls.Choroidal thickness(CT)was measured in the subfoveal region.Total circumscribed choroidal area(CA),luminal area(LA),stromal area(SA),and choroidal vascularity index(CVI)was calculated using Image J.RESULTS:At baseline,subfoveal CT was increased in n AMD patients compared to controls(P=0.321).Eyes with n AMD had a significantly increased total circumscribed CA and SA(P=0.041,0.005,respectively).The CVI was decreased(P=0.038).In the 3^(rd) month,the subfoveal CT,LA,and CVI revealed a decrease(P=0.005,P=0.039,0.043,respectively).In the 12th month,subfoveal CT,LA,and CVI were decreased in comparison to baseline measures(P<0.001,0.006,0.010,respectively).CONCLUSION:Significant structural alterations are found after intravitreal aflibercept treatment during the 12-month follow-up,in particular at the third month,in eyes with n AMD.

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.

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.

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.

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.