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.

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.

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.

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.

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.

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.

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.

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. RESULTS: The mean BCVA and CMT of 66 eyes(63 patients) were 1.11±0.60, 533.20±219.95 μm at baseline, and were 0.68±0.38, 310.28±125.60 μm at 3 mo. No subjects were lost during the first three months, the improvements were all significantly(P<0.05). During the whole follow-up time of 12 mo, 15 subjects(18 eyes) were lost. The mean BCVA and CMT of the rest 48 eyes with the follow-up time at least 1 y were 0.83±0.46 and 547.59±196.77 μm at baseline, after 3 mo and 12 mo of conbercept injections became 0.55±0.41, 318.24±141.29 μm and 0.55±0.51, 333.87±173.25 μm. The differences were significant(P<0.05). No serious complications were observed. CONCLUSION: Intravitreal injection of conbercept appears to significantly improve visual acuity and anatomical outcomes in patients with neovascular AMD, no serious adverse reactions and complications are observed.

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.

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.

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.