Ocular flora in patients undergoing intravitreal injections: antibiotic resistance patterns and susceptibility to antiseptic picloxydine

AIM: To study antibiotic resistance patterns and susceptibility to eye antiseptic picloxydine of conjunctival flora in patients undergoing intravitreal injections(IVIs).METHODS: Conjunctival swabs were taken in 4 groups of patients, 20 patients in each group(n=80): without IVIs and ophthalmic operations in history(group N1;control group);with the first IVI and antibiotic eye drops Tobrex applied 3 d before IVI and 5 d after it(group N2);with 20 or more IVIs and repeated courses of antibiotic eye drops(group N3);with the first IVI and antiseptic eye drops Vitabact(picloxydine) applied 3 d before IVI and 5 d after it(group N4). In groups N2 and N4 swabs were taken at baseline and after the treatment. Efficacy of picloxydine in inhibition of growth of conjunctival isolates susceptible and resistant to antibiotic was studied in vitro. Minimal inhibition concentrations(MIC) were determined with microdilution test.RESULTS: Two of the three patients who had to undergo the IVI procedure showed conjunctiva bacterial contamination. Along with few Staphylococcus aureus and Gram-negative isolates susceptible to most antibiotics, the majority(71%-77%) of causative agents were coagulase-negative Staphylococci(Co NS), 40%-50% of which were multidrug resistant(MDR). Eye disinfection in the operating room and peri-injection courses of Tobrex or Vitabact resulted in total elimination of isolates found at baseline. However, in 10% and 20% of patients, respectively, recolonization of the conjunctiva with differing strains occurred. In patients with repeated IVI and Tobrex/Maxitrol treatment, the conjunctival flora showed high resistance rates: 90% of Co NS were MDR. In the in vitro study, picloxydine showed bactericidal effect against Staphylococci isolates both antibiotic resistant and susceptible with MIC≥13.56 μg/m L. Incubation of bacteria for 15 min in Vitabact eye drops, commercially available form of picloxydine, 434 μg/m L, showed total loss of colony forming units of all tested isolates including Pseudomonas aeruginosa. CONCLUSION: The confirmed efficacy of eye antiseptic picloxydine against conjunctival bacterial isolates and the presence of its commercial form, 0.05% eye drops, convenient for use by patients before and after injection, make this eye antiseptic promising for prophylaxis of IVIassociated infectious complications.

Comment on bilateral same-session intravitreal injections

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

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.

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.

Paracentesis following intravitreal drug injections in maintaining physiologic ocular perfusion pressure

A retrospective analysis was performed of patients who received a paracentesis immediately following an intravitreal injection of bevacizumab or triamcinolone acetonide.These patients were previously diagnosed as having glaucoma,ocular hypertension,or had responded previously with sustained elevated intraocular pressure.Of 1661 procedures were performed.Totally 219（13%） of the injections were on phakic patients.A median（SD） of 210 μL（40 μL） of aqueous was removed during each paracentesis.There were no reported incidences of any complications.We propose performing a paracentesis immediately following intravitreal injections for patients at risk for ocular hypertension,glaucoma,and retinal vein or artery occlusion.

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study

Dear Sir,Ifound the article by Sobac1etal[1]very interesting.The authors concluded that repeated intravitreal injection(IVI)of ranibizumab or bevacizumab didn’t seem have adverse effects on retinal nerve fiber layer(RNFL)thickness in wet age-related macular degeneration(AMD)patients.

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.

Therapeutic potential of intravitreal pharmacotherapy in retinal vein occlusion

Retinal vein occlusion (RVO) is the most common visually disabling disease affecting the retina after diabetic retinopathy. Although the disease entity has long been known, its management is still controversial. Macular edema is the main reason for decreased visual acuity (VA) in this retinal vascular disorder. Recently the vitreous cavity has increasingly been used as a reservoir of drugs for the direct treatment of macular edema through intravitreal injection route. The most widely injected drugs so far have been triamcinolone acetonide (TA) and bevacizumab. The objective of this review is to evaluate the evidence and discuss the rationale behind the recent suggestions that intravitreal pharmacotherapy by corticosteroids and anti-vascular endothelial growth factors may be useful in the treatment of retinal vein occlusion.

Effects of two different doses of intravitreal bevacizumab on subfoveal choroidal thickness and retinal vessel diameter in branch retinal vein occlusion

AIM： To investigate the effects of two different doses of intravitreal bevacizumab on subfoveal choroidal thickness （SFChT） and retinal vessel diameter in patients with branch retinal vein occlusion. METHODS： An interventional, restrospective study of 41 eyes of 41 patients who had completed 12mo of follow-up, divided into group 1 （1.25 mg of bevacizumab, 21 eyes of 21 patients） and group 2 （2.5 mg of bevacizumab, 20 eyes of 21 patients）. Complete ophthalmic examination, fluorescein angiography, enhanced depth imaging optical coherence tomography and measurement of retinal vessel diameter with IVAN software were performed at baseline and follow-up. RESULTS： The SFChT changed from 279.1 （165-431） μm at baseline to 277.0 （149-413） μm at 12mo in group 1 （P= 0.086）, and from 301.4 （212-483） μm to 300.3 （199-514） μm in group 2 （P=0.076）. The central retinal arteriolar equivalent （CRAE） changed from 128.8 ±11.2 μm at baseline to 134.5±8.4 μm at 12mo in group 1, and from 134.6±9.0 μm to 131.4±12.7 μm in group 2 （P =0.767）. The central retinal venular equivalent （CRVE） changed from 204.1±24.4 μm at baseline to 196.3±28.2 μm at 12mo in group 1, and from 205.8±16.3 μm to 194.8±18.2 μm in group 2 （P=0.019）. The mean central macular thickness （P〈0.05） and average best-corrected visual acuity （BCVA; P〈0.05） improved in both groups CONCLUSION： Changes in the SFChT are not statistically significant and not different according to the doses of bevacizumab. The CRAE did not show significant change, however, the CRVE showed significant decrease regardless of the dose.

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.

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.

Intravitreal bevacizumab and Ahmed glaucoma valve implantation in patients with neovascular glaucoma

AIM:To explore the efficacy of preoperative intravitreal bevacizumab(IVB) injection combined with Ahmed glaucoma valve(AGV) implantation in the treatment of neovascular glaucoma(NVG).METHODS:This retrospective study included 35 eyes from 35 patients who underwent preoperative IVB and AGV implantation for treatment of NVG. Findings such as intraocular pressure(IOP) number of anti-glaucoma medications, visual acuity(VA), surgical success rates,and complications were recorded.RESULTS:AfterAGVimplantation,IOPwas18.2±4.0mmHg,15.5±3.3 mm Hg and 9.8±2.6 mm Hg at 6, 12 and 36 mo,significantly decreased compared with pre-IOP(P 【0.01).The number of anti-glaucoma medications was 0.9 ±0.5,0.8 ±0.9 and 0.8 ±0.6 at 6, 12 and 36 mo, significantly decreased compared to pre-treatment(P 【0.01). At last visit, there were 19 eyes with stable VA, 4 with VA improvement, 12 with diminished VA and 3 with complete loss light perception. There were 7 cases that failed during 3-year fellow up period. Cumulative probabilities of valve survival by Kaplan-Meier analysis were 82.9%,74.1% and 71.0% at 12, 24 and 36 mo, respectively. Cox stepwise regression analysis found that the survival time was significant associated with the pre-visual acuity 【2/400(P 【0.05). Post-operative complications occurred in 8eyes, of which hyphema presented in 2 eyes, choroidal effusion in 2 eyes.CONCLUSION:The procedure of preoperative IVB andAGV implantation should be one of treatments for NVG because of its safety and effectiveness.

Macular laser photocoagulation with or without intravitreal triamcinolone pretreatment for diabetic macular edema： a result from five randomized controlled trials

AIM：To assess possible benefits of intravitreal triamcinolone acetonide（IVTA）injection as pretreatment for macular laser photocoagulation（MLP）in patients with diabetic macular edema（DME）.·METHODS：Published randomized controlled trials（RCTs）concerning MLP with or without IVTA pretreatment for DME were retrieved from databases CNKI,Medline,EMbase,Web of Science,and the Cochrane Library.A Meta-analysis on eligible studies was conducted using Rev Man 5.0 software.Two investigators independently assessed the quality of the trials and extracted data.Main outcome measures included the change in best-corrected visual acuity（BCVA）,difference in central macular thickness（CMT）and adverse events reporting in particular elevated intraocular pressure within the follow-up period.The results were pooled using weight mean difference（WMD）or odds risk（OR）with their corresponding 95%confidence intervals（CI）.A fixed-or random-effect model was employed depending on the heterogeneity of the inclusion trials.·R ESULTS：Finally,five independent RCTs were identified and used for comparing MLP with IVTA pretreatment（131 eyes）with MLP alone（133 eyes,control group）.The overall study quality was relatively higher according to the modified Jadad scale.The Metaanalysis showed that MLP with IVTA pretreatment significantly reduced CMT at one,three and six months（=0.002,0.0003 and 0.04,respectively）,compared with MLP alone.The IVTA pretreatment group showed statistically significant improvements in BCVA at the one-month follow up as compared with the control group（=0.03）.At three-and six-month follow up,there was a beneficial trend towards improving visual acuity in the IVTA pretreatment group without statistical significance between groups（=0.06 and 0.20,respectively）.The incidence of elevation of intraocular pressure was significantly higher in the IVTA pretreatment group than in the control group（〈0.0001）.No evidence of publication bias was present according to Begg’s test and Egger’s test.There was a low level of heterogeneity in the included studies.·CONCLUSION：This Meta-analysis indicates that MLP with IVTA pretreatment has a better therapeutic effect in terms of CMT reduction and earlier（1mo）visual improvement for patients with DME as compared with MLP alone.Further confirmation with rigorously welldesigned multi-center trials is needed.

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.

Intravitreal stem cell paracrine properties as a potential neuroprotective therapy for retinal photoreceptor neurodegenerative diseases

Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs.

Comparison of intravitreal bevacizumab with macular photocoagulation for treatment of diabetic macular edema: a systemic review and Meta-analysis

AIM: To further evaluate the efficacy and safety of intravitreal bevacizumab(IVB) versus macular photocoagulation(MPC) in treatment of diabetic macular edema(DME) by Meta-analysis. METHODS: Pertinent publications were identified through systemic searches of Pub Med, Medline,EMBASE, and the Cochrane Controlled Trials Register up to 30 November, 2013. Changes in central macular thickness(CMT) in μm and best-corrected visual acuity(BCVA) in log MAR equivalents were extracted at 1, 3, 6,12 and 24 mo after initial treatment, and a Meta-analysis was carried out to compare results between groups receiving IVB and MPC.RESULTS: Five randomized controlled trial(RCTs) and one high-quality comparative study were identified and included. Our Meta-analysis revealed that both IVB and MPC resulted in the improvements of CMT and BCVA in eyes with DME at 1mo after initial treatment, with IVB being significantly superior to MPC(P =0.01 and 0.02,respectively). The improvements of both measure outcomes at 3, 6, 12 and 24 mo after treatment did not vary significantly between the IVB groups and MPC groups(CMT at 3mo, P =0.85; at 6mo, P =0.29; at 12 mo,P =0.56; at 24 mo, P =0.71; BCVA at 3mo, P =0.31; at 6mo,P =0.30; at 12 mo, P =0.23; at 24 mo, P =0.52). However,the number of observed adverse events was low in all studies.CONCLUSION: Current evidence shows IVB treatment trends to be more effective in improvements of macular edema and vision in eyes with DME at an earlier follow up(1mo) compared with MPC. At other time, both interventions have comparable efficacy without statistical significances.

Predictors of short-term outcomes related to central subfield foveal thickness after intravitreal bevacizumab for macular edema due to central retinal vein occlusion

AIM：To investigate the predictive factors for shortterm effects of intravitreal bevacizumab injections on central subfield foveal thickness（CSFT）in patients with macular edema（ME）secondary to central retinal vein occlusion（CRVO）.·METHODS：This was a retrospective study in 60 eyes treated with intravitreal bevacizumab injections for ME due to CRVO.Follow-up was three months.The Early Treatment Diabetic Retinopathy Study（ETDRS）score and CSFT measured by spectral-domain optical coherence tomography（SD-OCT）were used to observe the changes in best-corrected visual acuity（BCVA）.Baseline BCVA,CSFT,age,CRVO duration and the presence of cystoid macular edema（CME）or subretinal fluid（SRF）were analyzed as potential predictive factors of the effects of intravitreal bevacizumab injections.·R ESULTS：BCVA improved from 0.9 log MAR at baseline to 0.6 log MAR at 3mo,which was associated with a significant reduction in CSFT from 721μm to 392μm 3mo after injection.About 50%of CME cases and more than90%of SRF cases responded to treatment with a complete resolution at 3mo.Age（=0.036）and low baseline CSFT（=0.037）were associated with a good 3-month prognosis.Patients〉60 years old achieved better CME resolution（=0.031）and lower CSFT at 3mo（305μm 474μm,=0.003）.·CONCLUSION：Intravitreal bevacizumab significantly improved visual acuity and CSFT in patients with CRVO after 3mo.Older age and lower baseline CSFT were good predictors of short-term CSFT outcomes.The retinal thickness response to bevacizumab might depend on the resolution of CME rather than SRF.

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.

Improvement of visual acuity based on optical coherence tomography patterns following intravitreal bevacizumab treatment in patients with diabetic macular edema

AIMTo report the visual outcome based on various patterns of optical coherence tomography (OCT) morphology in diabetic macular edema (DME), following treatment with anti-VEGF intravitreal bevacizumab (IVB) injection.