Science.gov

Sample records for intravitreal injection analysis

  1. Intravitreal injection

    MedlinePlus

    ... You may have this procedure if you have: Macular degeneration : An eye disorder that slowly destroys sharp, central ... injection References American Academy of Ophthalmology. Age-related macular degeneration PPP - updated 2015. Aao.org web site. Updated ...

  2. Intravitreal injections: what do patients prefer? Analysis of patient's satisfaction and preferences about where to perform intravitreal injections.

    PubMed

    Rodríguez Ramírez, M; del Barrio Manso, M I; Martín Sánchez, M D

    2014-12-01

    To analyse satisfaction and patient preferences on the location where they receive an intravitreal injection. A survey was conducted with the intention of analysing these patients who attended the macula clinic and have been intervened using an intravitreal injection at least once in the day hospital or in the theatre setting, comparing both locations. The majority of the interviewed patients preferred the day hospital (50.0 versus 37.5%), mostly because of the comfort and the quick service. In patients with severe age-related macular degeneration (AMD) the option is reversed. The overall satisfaction level was positive in both cases (with 87.5% of patients satisfied or very satisfied in the day hospital and 91.1% in the theatre setting). Through the analysis of different aspects of clinical care the assessment was the same or superior for 75.0% of these patients, except in the waiting time. There were no cases of endophthalmitis. In general, patients prefer the clinical intervention in the consulting room than in the theatre setting because of the quicker service. There are several characteristics that can influence this choice and should be taken into account. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  3. Antibioprophylaxis in Prevention of Endophthalmitis in Intravitreal Injection: A Systematic Review and Meta-Analysis

    PubMed Central

    Benoist d’Azy, Cédric; Pereira, Bruno; Naughton, Geraldine; Chiambaretta, Frédéric; Dutheil, Frédéric

    2016-01-01

    Despite endophthalmitis being the most feared complication, antibioprophylaxis remains controversial in intravitreal injections. Therefore, we conducted a systematic review and meta-analysis on the effects of antibioprophylaxis in intravitreal injections in the prevention of endophthalmitis. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies comparing groups with and without antibiotics in intravitreal injection, with the use of the following keywords: "antibiotic*", "endophthalmitis" and “intravitreal injection*”. To be included, studies needed to specify number of participants and number of endophthalmitis within each group (with and without antibiotics). We conducted meta-analysis on the prevalence of clinical endophthalmitis including both culture-proven and culture negative samples. Nine studies were included. A total of 88 incidences of endophthalmitis were reported from 174,159 injections (0.051% i.e., one incidence of endophthalmitis for 1979 injections). Specifically, 59 incidences of endophthalmitis were reported from 113,530 injections in the group with antibiotics (0.052% or one incidence of endophthalmitis for 1924 injections) and 29 incidences of endophthalmitis from 60,633 injections in the group without antibiotics (0.048% or one endophthalmitis for 2091 injections). Our meta-analysis did not report a significant difference in the prevalence of clinical endophthalimitis between the two groups with and without topical antibiotics: the odds ratio of clinical endophthalimitis was 0.804 (CI95% 0.384–1.682, p = 0.56) for the antibiotic group compared with the group without antibiotics. In conclusion, we performed the first large meta-analysis demonstrating that antibioprophylaxis is not required in intravitreal injections. Strict rules of asepsis remain the only evidence-based prophylaxis of endophthalmitis. The results support initiatives to reduce the global threat of resistance to antibiotics. PMID

  4. Antibioprophylaxis in Prevention of Endophthalmitis in Intravitreal Injection: A Systematic Review and Meta-Analysis.

    PubMed

    Benoist d'Azy, Cédric; Pereira, Bruno; Naughton, Geraldine; Chiambaretta, Frédéric; Dutheil, Frédéric

    2016-01-01

    Despite endophthalmitis being the most feared complication, antibioprophylaxis remains controversial in intravitreal injections. Therefore, we conducted a systematic review and meta-analysis on the effects of antibioprophylaxis in intravitreal injections in the prevention of endophthalmitis. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies comparing groups with and without antibiotics in intravitreal injection, with the use of the following keywords: "antibiotic*", "endophthalmitis" and "intravitreal injection*". To be included, studies needed to specify number of participants and number of endophthalmitis within each group (with and without antibiotics). We conducted meta-analysis on the prevalence of clinical endophthalmitis including both culture-proven and culture negative samples. Nine studies were included. A total of 88 incidences of endophthalmitis were reported from 174,159 injections (0.051% i.e., one incidence of endophthalmitis for 1979 injections). Specifically, 59 incidences of endophthalmitis were reported from 113,530 injections in the group with antibiotics (0.052% or one incidence of endophthalmitis for 1924 injections) and 29 incidences of endophthalmitis from 60,633 injections in the group without antibiotics (0.048% or one endophthalmitis for 2091 injections). Our meta-analysis did not report a significant difference in the prevalence of clinical endophthalimitis between the two groups with and without topical antibiotics: the odds ratio of clinical endophthalimitis was 0.804 (CI95% 0.384-1.682, p = 0.56) for the antibiotic group compared with the group without antibiotics. In conclusion, we performed the first large meta-analysis demonstrating that antibioprophylaxis is not required in intravitreal injections. Strict rules of asepsis remain the only evidence-based prophylaxis of endophthalmitis. The results support initiatives to reduce the global threat of resistance to antibiotics.

  5. Pharmacokinetic analysis of topotecan after intra-vitreal injection. Implications for retinoblastoma treatment.

    PubMed

    Buitrago, Emiliano; Höcht, Christian; Chantada, Guillermo; Fandiño, Adriana; Navo, Elliot; Abramson, David H; Schaiquevich, Paula; Bramuglia, Guillermo F

    2010-07-01

    Topotecan is a promising drug with activity against retinoblastoma, however, attaining therapeutic concentrations in the vitreous humor is still a challenge for the treatment of vitreous seeds in retinoblastoma. Our aim was to characterize topotecan pharmacokinetics in vitreous and aqueous humor, and to assess the systemic exposure after intra-vitreal injection in rabbits as an alternative route for maximizing local drug exposure. Anesthetized rabbits were administered intra-vitreal injections of 5 microg of topotecan. Vitreous, aqueous, and blood samples were collected at pre-defined time points. A validated high-performance liquid chromatography assay was used to quantitate topotecan (lactone and carboxylate) concentrations. Topotecan pharmacokinetic parameters were determined in vitreous, aqueous and plasma using a compartmental analysis. Topotecan lactone concentrations in the vitreous of the injected eye were about 8 ng/mL 48 h after drug administration. The median maximum vitreous, aqueous and plasma total topotecan concentrations (C(max)) were 5.3, 0.68 and 0.21 microg/mL, respectively. The C(max) vitreous/aqueous of treated eyes and the C(max) vitreous/plasma were approximately 8 and 254, respectively. Total topotecan exposure (AUC) in the vitreous of the injected eye was 50 times greater than the total systemic exposure. These findings suggest that intra-vitreal administration of only 5 microg of topotecan reaches significant local levels over an extended period of time while minimizing systemic exposure in the rabbit. Intra-vitreal topotecan administration offers a promising alternative route for enhanced drug exposure in the vitreous humor with potential application for treatment of vitreal seeds in retinoblastoma while avoiding systemic toxicities.

  6. Intravitreal Injection-Induced Migraine Headaches

    PubMed Central

    Lerebours, Valerie C; Nguyen, Thanh-Giao; Sarup, Vimal; Rossi, Fabian

    2016-01-01

    A case of migraine headache triggered by intravitreal injection, and aborted by retrobulbar injection, is reported. To date, migraine and related cephalgia have not been reported after intravitreal injection. Ophthalmologists and neurologists should be aware of this potential sequela of a very common procedure.  PMID:27190726

  7. Intravitreal anti-VEGF injections for treating wet age-related macular degeneration: a systematic review and meta-analysis.

    PubMed

    Ba, Jun; Peng, Run-Sheng; Xu, Ding; Li, Yan-Hong; Shi, Hui; Wang, Qianyi; Yu, Jing

    2015-01-01

    Age-related macular degeneration (AMD) is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD. A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA), retinal thickness, and lesion size were evaluated. Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR) group and the intravitreal bevacizumab group (standard mean difference = -0.14, 95% confidence interval [CI] = -0.23 to -0.05). No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN) can raise VA by 1.97 letters (weighted mean difference = 1.97, 95% CI = 0.14-3.794). Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference = 2.74, 95% CI = 0.26-5.21). The superiority remains unclear between IVR and intravitreal bevacizumab in the treatment of neovascular AMD. Intravitreal aflibercept dosed every 2 months required fewer injection times, but produced similar efficacy as monthly IVR. IVR PRN could significantly increase VA. Combined with photodynamic therapy, IVR therapy could also increase VA effectively.

  8. Ocular toxicity after intravitreal injection of terconazole.

    PubMed

    Schulman, J A; Peyman, G A; Dietlein, J; Fiscella, R; Colantino, B

    1989-09-01

    Terconazole, a new triazole antifungal agent, was injected intravitreally in doses ranging from 10 to 100 micrograms dissolved in dimethyl sulfoxide (DMSO) 60% into the eyes of New Zealand rabbits. Three control eyes received only DMSO. The eyes were evaluated with biomicroscopy, indirect ophthalmoscopy, electroretinography, and histopathologic examination. From these data, it was determined that an intravitreal injection containing a concentration of 10 micrograms/0.1 mL of terconazole is not toxic to the rabbit eye.

  9. Assistive Device for Efficient Intravitreal Injections.

    PubMed

    Ullrich, Franziska; Michels, Stephan; Lehmann, Daniel; Pieters, Roel S; Becker, Matthias; Nelson, Bradley J

    2016-08-01

    Intravitreal therapy is the most common treatment for many chronic ophthalmic diseases, such as age-related macular degeneration. Due to the increasing worldwide demand for intravitreal injections, there exists a need to render this medical procedure more time- and cost-efficient while increasing patient safety. The authors propose a medical assistive device that injects medication intravitreally. Compared to the manual intravitreal injection procedure, an automated device has the potential to increase safety for patients, decrease procedure times, allow for integrated data storage and documentation, and reduce costs for medical staff and expensive operating rooms. This work demonstrates the development of an assistive injection system that is coarsely positioned over the patient's head by the human operator, followed by automatic fine positioning and intravitreal injection through the pars plana. Several safety features, such as continuous eye tracking and iris recognition, have been implemented. The functioning system is demonstrated through ex vivo experiments with porcine eyes. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:752-762.].

  10. Adverse skin reactions following intravitreal bevacizumab injection

    PubMed Central

    Ameen, S; Entabi, M; Lee, N; Stavrakoglou, A

    2011-01-01

    The authors describe two separate cases of skin eruption following intravitreal bevacizumab injection with evidence to suggest that these were adverse drug reactions to bevacizumab. The authors also discuss how each case was treated and report on the final outcome. PMID:22715260

  11. [Membrane peeling combined with intravitreal injection of bevacizumab for treatment of macular epiretinal membrane: analysis of 33 cases].

    PubMed

    Li, Zhiqiang; Zhang, Guoming; Su, Kangjin; Song, Xiangmei; Tian, Ruyin; Gu, Xunqing

    2014-07-01

    To assess efficacy of membrane peeling combined with intravitreal injection of bevacizumab in the treatment of macular epiretinal membrane. From January, 2012 to June, 2013, 33 patients (33 eyes) with the diagnosis of macular epiretinal membrane underwent vitreous surgery and membrane peeling. The patients were randomly divided into intravitreal bevacizumab group (IVB group) and non-intravitreal bevacizumab group (non-IVB group). All the patients underwent standard three-port vitrectomy and peeling of epiretinal membrane, with intravitreal injection of 1.5 mg bevacizumab at the end of operation in IVB group. The best corrected visual acuity and optical coherence tomography (OCT) were examined before and after the treatment. The patients were followed up for 3-14 months (mean 6.5 months). Macular epiretinal membranes were successfully peeled during operation in all the patients without postoperative intraocular infection or bleeding. Fifteen eyes received vitrectomy combined with intravitreal injection of bevacizumab, and 18 underwent only vitreous operation and membrane peeling. At the end of the follow up, the visual acuity improved in 11 eyes (73.3%) in IVB group, as compared to 13 eyes (72.2%) in the non-IVB group (P=0.627). Central macular thickness decreased by 143∓62 µm in IVB group and by 96∓28 µm in non-IVB group, showing a significant difference between the two groups (t=5.564, P<0.01). Vitrectomy and membrane peeling combined with intravitreal injection of bevacizumab can promote the recovery of macular morphology but not visual function, and its clinical use still needs to be tested in a long-term and large-sample randomized controlled study.

  12. Intravitreal injections inducing de quervain tenosynovitis: injector's wrist.

    PubMed

    Belliveau, Michel J; Leung, Christina; Abouammoh, Marwan A

    2015-01-01

    To describe a case of de Quervain tenosynovitis triggered by the repetitive performance of intravitreal injections. Case report of a 32-year-old ophthalmologist. The ophthalmologist experienced de Quervain tenosynovitis while performing 425 intravitreal injections a month. These were predominantly performed in condensed sessions (injection clinics). Symptoms resolved with nonsurgical management. The repetitive performance of intravitreal injections may be an unrecognized occupational hazard for ophthalmologists.

  13. Experimental model of intravitreal injection techniques.

    PubMed

    Hubschman, Jean-Pierre; Coffee, Robert E; Bourges, Jean-Louis; Yu, Fei; Schwartz, Steven D

    2010-01-01

    To evaluate the amount of drug reflux and vitreous leakage from the needle tract after various intravitreal (IVT) injection techniques in porcine cadaver eyes. The reflux after IVT injection was quantified by methylene blue injection through the pars plana of fresh pig eyes (0.05 mL per eye, n = 150) and the vitreous incarceration measured after balanced salt solution (BSS) IVT injection (0.05 mL per eye, n = 150) into eyes with vitreous previously stained with methylene blue. Blue spots observed on the ocular surface after injection quantified both reflux and vitreous incarceration. We tested different needle sizes (27, 30, and 32 gauge) and different techniques (depth and speed of injection). We used an ocular endoscope to observe the flow and diffusion of injected methylene blue and the vitreous incarceration at the puncture site after IVT injection using the different techniques. Thirty-gauge needles showed less drug reflux than the 32-gauge or 27-gauge needles (P < 0.01). Thirty-two-gauge needles demonstrated less incarceration of vitreous at the tract site (P < 0.01), but with the endoscope, all needle tracts showed vitreous incarceration at their internal aspect. Deep IVT injection showed less reflux than superficial IVT injection, but vitreous incarceration did not differ. The delay between the scleral puncture and the injection did not modify the reflux or the vitreous incarceration. Thirty-gauge needles and deep placement of the needle tip into the vitreous before injection may reduce reflux and vitreous incarceration. This could maximize the therapeutic effect of IVT injection and may decrease the rates of severe complications such as retinal detachment and endophthalmitis.

  14. [Viral retinitis following intravitreal triamcinolone injection].

    PubMed

    Zghal, I; Malek, I; Amel, C; Soumaya, O; Bouguila, H; Nacef, L

    2013-09-01

    Necrotizing viral retinitis is associated with infection by the Herpes family of viruses, especially herpes simplex virus (HSV), varicella zoster virus (VZV) and occasionally cytomegalovirus (CMV). When the diagnosis is suspected clinically, antiviral therapy must be instituted immediately. We report the case of a patient presenting with necrotizing viral retinitis 3 months following intravitreal injection of triamcinolone acetonide for diabetic macular edema. Fluorescein angiography demonstrated a superior temporal occlusive vasculitis. A diagnostic anterior chamber paracentesis was performed to obtain deoxyribo-nucleic acid (DNA) for a polymerase chain reaction (PCR) test for viral retinitis. PCR was positive for CMV. The patient was placed on intravenous ganciclovir. CMV retinitis is exceedingly rare in immunocompetent patients; however, it remains the most common cause of posterior uveitis in immunocompromised patients. The incidence of this entity remains unknown. Local immunosuppression, the dose and the frequency of injections may explain the occurrence of this severe retinitis.

  15. Experience of intravitreal injections in a tertiary Hospital in Oman

    PubMed Central

    Al-Hinai, Ahmed S.

    2015-01-01

    Aim: To find out statistical data regarding intravitreal injections in an outpatient department setup at a tertiary center in Oman. Design: Retrospective chart review. Methods: Data collection of patients who underwent intravitreal injections from November 2009 to May 2013 at Sultan Qaboos University Hospital. Results: Throughout a period of 42 months, a total of 711 intravitreal injections were performed. That included 214 patients (275 eyes). Around one-third of the eyes received two injections or more. The injected agents were bevacizumab (59.8%), ranibizumab (32.3%), triamcinolone (7.5%), and very few patients with endophthalmitis received intravitreal antibiotics and antifungal agents. The three most common indications for the injection therapy were diabetic macular edema (50.9%), choroidal neovascularization (24.3%), and retinal vein occlusive diseases (11.5%). Serious adverse events were rare, and they occurred as ocular (0.9% per patient) and systemic (3.3% per patient). There were 42 eyes received intravitreal triamcinolone, and 24% of them developed intraocular hypertension that required only medical treatment. Conclusion: Different intravitreal agents are currently used to treat many ocular diseases. Currently, therapy with intravitreal agents is very popular, and it carries a promising outcome with more efficiency and safety. PMID:26903722

  16. Ultrasound biomicroscopy study of vitreous incarceration subsequent to intravitreal injections.

    PubMed

    Hodjatjalali, Kamran; Riazi, Mohammad; Faghihi, Hooshang; Khorami, Azita

    2012-02-01

    To study the existence of vitreous incarceration by ultrasound biomicroscopy (UBM) at the pars plana after direct intravitreal injection of triamcinolone acetonide ± bevacizumab without anterior chamber paracentesis. Interventional case series. Patients undergoing intravitreal injection of triamcinolone acetonide with or without intravitreal bevacizumab. In 21 eyes, the existence of vitreous incarceration at the pars plana site of intravitreal injection of 0.05 mL of drug was studied by UBM (50 MHz probe of the VUmax, Sonomed, NY), the day after surgery, by 1 technician. The reason for injection was diabetic retinopathy in 12 (57.1%) eyes; age-related macular degeneration in 6 (28.6%) eyes; branch retinal vein occlusion in 2 (9.5%) eyes; and choroiditis in 1 eye (4.8%). In 1 eye, only triamcinolone acetonide was injected, and in the other eyes, bevacizumab mixed with triamcinolone acetonide was injected. We studied 21 eyes in 13 patients. Of the subjects, 61.5% were male. The mean age of the patients was 62.2 years. On the day after intravitreal injection of the drug, vitreous incarceration into the pars plana site was detected by UBM in 42.9% of the eyes. Vitreous incarceration exists after intravitreal injection of drug, but its clinical importance is still unknown. Further long-term prospective studies are recommended. Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  17. Contact dermatitis in patients undergoing serial intravitreal injections.

    PubMed

    Veramme, Jolien; de Zaeytijd, Julie; Lambert, Jo; Lapeere, Hilde

    2016-01-01

    Anti-vascular endothelial growth factor (VEGF) medication, injected intravitreally, is currently the standard of care in patients with different retinal pathologies. Since its introduction in 2006, an increasing number of patients have undergone this procedure in Ghent University Hospital. Strikingly, more patients were diagnosed with contact dermatitis caused by ophthalmic products used during intravitreal injection procedure. To identify which of the substances used during intravitreal injection is most likely to cause contact dermatitis. Sixteen patients who developed a burning and stinging sensation and swelling of the eyelids after intravitreal injection were tested. All patients were patch tested with the Belgian baseline series, as well as a cosmetic, a pharmaceutical and an ophthalmic series, including the different eye drops used during the intravitreal injection procedure. Fourteen of 16 patients reacted to at least one of the substances used during the injection procedure. Nine patients reacted to phenylephrine (56%), 5 to iso-Betadine(®) ophthalmic solution (31%), and 3 patients to sodium metabisulfite (16%). The most common causal allergen was phenylephrine, being positive in 56% of patients. Patients most likely become sensitized because of the high frequency of usage of phenylephrine during repeated intravitreal injections and follow-up consultations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Visual perceptions induced by intravitreous injections of therapeutic agents

    PubMed Central

    Charalampidou, S; Nolan, J; Ormonde, G O; Beatty, S

    2011-01-01

    Purpose The purpose of this study was to conduct a questionnaire-based survey of subjective visual perceptions induced by intravitreous (IVT) injections of therapeutic agents. Patients and methods Patients undergoing an IVT injection of ranibizumab, pegaptanib sodium, or triamcinolone acetonide were administered a questionnaire in the immediate post-injection period and at 2 weeks of follow-up. Results In the immediate post-injection period (75 IVT injections, 75 eyes, 75 patients), lights and floaters were reported after 20 (27%) and 24 (32%) IVT injections, respectively. In comparison, at the 2-week follow-up, the incidence of reported lights (11; 15%) was similar (P>0.05), but the incidence of reported floaters was higher (48; 64% P=0.00). Subgroup analysis for various injection subgroups (no previous injection vsprevious injection(s) in the study eye; injections in study eyes with good VA (logarithm of minimal angle of resolution [logMAR] ≤0.3) vsmoderate VA (0.7 0.3) vspoor VA (logMAR ≥0.7); injections according to pharmacological agent (ranibizumab vspegaptanib vstriamcinolone acetonide); injections in study eyes with choroidal neovascularization (of various causes) vsstudy eyes with macular edema (of various causes); and injections in phakic vspseudophakic eyes) did not reveal any statistically significant associations. Visual perceptions experienced following 15% of IVT injections gave cause for concern to the patient (mean visual analog scale score (±SD): 4.5 (±1.7)), and in 64% of cases, the patients believed that preoperative counseling would have averted the concern. Conclusions Lights and floaters are frequent visual perceptions following IVT injections of therapeutic agents. They can give rise to concern that could be alleviated with preinjection counseling. PMID:21274011

  19. Tower microneedle minimizes vitreal reflux in intravitreal injection.

    PubMed

    Lee, Chang Yeol; You, Yong Sung; Lee, Sung Ho; Jung, Hyungil

    2013-10-01

    Intravitreal injection is widely used for easy control of drug levels in posterior segment of the eye by injecting the drug directly with hypodermic needles. Patients, however, often experience complications from intravitreal injection due to repeated injections, increased intraocular pressure, and infection. In addition, injected drug reflux after intravitreal injection makes it challenging to maintain predetermined drug dose due to the drug loss through backward effusions. Here, we described that the Tower Microneedle can reduce initial reflux and bleb formation due to its smaller outer diameter compared to a traditional hypodermic needle. Furthermore, we use phenylephrine hydrochloride for pupil expansion and demonstrated that Tower Microneedle induced similar pupil expansions using only half the drug volume, in the same period of time, compared to the 31 Gauge hypodermic needle. Consequently, Tower Microneedle achieves the same therapeutic effect in the vitreous body using fewer drugs than a traditional hypodermic needle due to the decreased backward drug effusion. Tower Microneedle described herein holds great promise for intravitreal injection with less reflux and lower drug dosage.

  20. Intravitreal injection of Bevacizumab in diabetic macular edema

    PubMed Central

    Ateeq, Asim; Tahir, Muhammad Ali; Cheema, Alyscia; Dahri, Arif; Tareen, Saifullah

    2014-01-01

    Objective: To assess the effectiveness of intravitreal injection of Bevacizumab in the treatment of diabetic macular edema. Methods: This case series was conducted at Department of Ophthalmology, Jinnah Post Graduate Medical Centre (JPMC), Karachi. The duration of study was six months from May 26, 2011 to November 25, 2011. The study group comprised of 54 patients of the Diabetic Macular Edema (DME). Intravitreal injection of 1.25 mg of bevacizumab (Avastin) was injected 3.5 mm from the limbus under topical anaesthetic drops. Post procedure follow up was scheduled on 1st post procedure day and after one month. Post procedure Optical Coherence tomography (OCT) was performed in all patients 1 week before and 1st month after 1st injection. The results were statistically analyzed through SPSS 17. Results: Out of the 54 Eyes of 54 Patients who were given the Intravitreal injection of Avastin (Bevacizumab), 43 Eyes (79.6%) showed more than ten percent decrease in macular thickness from pre-injection thickness, 10 Eyes (18.5%) showed less than ten percent decrease and 1 Eye (1.9%) showed increase in macular thickness post operatively after one month. Conclusions: Intravitreal injection of Bevacizumab (Avastin) is effective in the treatment of diabetic macular edema. PMID:25674143

  1. Air entry into the anterior chamber post intravitreal injection of Eylea.

    PubMed

    Lim, Wei Sing; Sikandar, Munir; Jackson, Heather

    2016-07-20

    An 84-year-old man had air entry into the anterior chamber following intravitreal injection. The air bubble was reabsorbed over time without any complications. No further problems occurred with subsequent intravitreal injections.

  2. Necrotizing herpetic retinopathy after intravitreal triamcinolone acetonide injection.

    PubMed

    Sisk, Robert A; Hutchins, Robert K

    2007-01-01

    To report a new complication of intravitreal triamcinolone acetonide (TA) injection. In this observational case report, an 87-year-old woman received an intravitreal injection of TA as an adjunct to photodynamic therapy for wet age-related macular degeneration in the left eye. Four months later, she developed ipsilateral necrotizing herpetic retinopathy (NHR). Retinal whitening of the macula was noted in the absence of vitritis that progressed over 5 days to diffuse retinitis with moderate vitritis and anterior chamber cell. Visual acuity decreased from 20/30 to 20/400. TA was still present inferiorly in the vitreous cavity. Polymerase chain reaction testing of samples obtained by vitrectomy with vitreous aspiration and retinal biopsy demonstrated varicella-zoster virus DNA. Two weeks later, repeated vitrectomy, silicone oil injection, and implantation of a ganciclovir sustained-release device were performed. Final visual acuity was 5/200. NHR can develop as a complication of intravitreal TA injection in an eye with a history of herpes zoster ophthalmicus.

  3. Endophthalmitis after resident-performed intravitreal bevacizumab injection.

    PubMed

    Falavarjani, Khalil Ghasemi; Aghamirsalim, Mohammadreza; Modarres, Mehdi; Hadavandkhani, Ali; Hashemi, Masih; Parvaresh, Mohammad Mehdi; Naseripour, Masood; Samiy, Nasrollah

    2015-02-01

    To evaluate the rate of acute endophthalmitis after resident-performed intravitreal bevacizumab (IVB) injections and to compare the results with those performed by attending retina surgeons. Retrospective comparative case series. Eight thousand thirty-seven patients treated with intravitreal injection of bevacizumab. A retrospective chart review of the resident-performed IVB injections at Rassoul Akram Hospital and attending-performed IVB injections at a private eye clinic between 2011 and 2014 was undertaken. Cases of clinical endophthalmitis were identified. During the study interval, the overall incidence rate of postinjection endophthalmitis was 0.01% (1/8037). Antibiotic eye drops were prescribed after IVB injection for 2771 eyes (34.5%). The single case of acute endophthalmitis occurred after a resident-performed injection, and vitreous culture showed growth of Staphylococcus epidermidis. The incidence rate of acute endophthalmitis after resident-performed IVB injection was 0.02% (1/4921). No statistically significant difference was found in the rates of endophthalmitis between resident-performed and attending-performed injections (p = 1). Also, the difference in the rates of endophthalmitis between those receiving postinjection antibiotics and those who did not was not statistically significant (p = 0.3). The risk for endophthalmitis after resident-performed IVB injection is low and similar to that of the supervising surgeons performing the procedure. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  4. Intravitreal injections: a review of the evidence for best practice.

    PubMed

    Fagan, Xavier J; Al-Qureshi, Salmaan

    2013-07-01

    Intravitreal injection is a common procedure performed by ophthalmologists. It is a quick and targeted treatment for a number of ophthalmic conditions. Despite this, the potential to cause serious complications and patient discomfort cannot be ignored. This article presents the level of evidence in the scientific literature supporting common practices such as location of the procedure, anaesthetic choice, sterile procedure techniques, comparison of some common pharmaceutical agents and the use of antibiotics.

  5. Topical azithromycin or ofloxacin for endophthalmitis prophylaxis after intravitreal injection

    PubMed Central

    Romero-Aroca, Pedro; Sararols, Laura; Arias, Lluis; Casaroli-Marano, Ricardo P; Bassaganyas, Francisca

    2012-01-01

    Background The number of patients who have undergone intravitreal injections has increased enormously in recent years, but a consensus is still lacking on prophylaxis for endophthalmitis. The aim of this prospective, observational study was to evaluate the prophylactic effect of azithromycin eye drops versus ofloxacin eye drops. Methods The study was conducted in five hospitals in Spain and included all patients undergoing intravitreal injections of triamcinolone, bevacizumab, ranibizumab, or pegaptanib over one year. Patients received azithromycin 15 mg/g eye drops (twice daily on the day prior to injection and for another 2 days) or ofloxacin 3 mg/g eye drops (every 6 hours on the day prior to injection and for another 7 days). Results In the azithromycin group, there were 4045 injections in 972 eyes of 701 patients. In the ofloxacin group, there were 4151 injections in 944 eyes of 682 patients. There were two cases of endophthalmitis (0.049%) in the azithromycin group and five (0.12%) in the ofloxacin group. The odds ratio of presenting with endophthalmitis in the ofloxacin group compared with the azithromycin group was 2.37 (95% confidence interval [CI] 1.32–3.72, P < 0.001). There were two cases of noninfectious uveitis after triamcinolone injection in the azithromycin group (0.049%) and two (0.048%) in the ofloxacin group; no significant differences were observed (odds ratio 0.902, 95% CI 0.622–1.407, P = 0.407). Conjunctival hyperemia was observed in 12 cases in the azithromycin group and none in the ofloxacin group. Conclusion The risk of endophthalmitis was significantly greater with ofloxacin than with azithromycin. These findings provide a valuable addition to the ever-increasing pool of information on endophthalmitis prophylaxis after intravitreal injection, although further large-scale studies are required to provide definitive conclusions. PMID:23109798

  6. Characterization of uveitis induced by use of a single intravitreal injection of bacterial lipopolysaccharide in cats.

    PubMed

    Del Sole, María J; Sande, Pablo H; Felipe, Antonio E; Fernandez, Diego C; Keller Sarmiento, María I; Aba, Marcelo A; Rosenstein, Ruth E

    2008-11-01

    To investigate the use of a single intravitreal injection of bacterial lipopolysaccharide (LPS) to experimentally induce uveitis in cats. 7 young male European shorthair cats that were considered physically and ophthalmologically healthy. In each cat, LPS was injected intravitreally into 1 eye; the contralateral eye was injected with the preparation vehicle. During a period of 45 days, both eyes were evaluated by means of clinical evaluation; assessment of the integrity of the blood-aqueous humor barrier (determined via measurement of protein concentration and cell content in samples of aqueous humor); functional analysis (via electroretinography); and following euthanasia, histologic examination of the retinas. In LPS-treated eyes, several clinical signs were observed until day 45 after injection. Compared with vehicle-treated eyes, intraocular pressure was significantly lower and protein concentration and the number of infiltrating cells were significantly higher in LPS-treated eyes. Mean amplitudes of scotopic electroretinographic a- and b-waves were significantly reduced in eyes injected with LPS, compared with findings in eyes injected with vehicle. At 45 days after injection, LPS-induced alterations in photoreceptors and the middle portion of the retina were detected histologically. Results indicated that a single intravitreal injection of LPS in eyes of cats induced clinical, biochemical, functional, and histologic changes that were consistent with the main features of naturally occurring uveitis. This technique may be a useful tool in the investigation of new treatment strategies for uveitis in cats.

  7. Establishment of a novel retinoblastoma (Rb) nude mouse model by intravitreal injection of human Rb Y79 cells - comparison of in vivo analysis versus histological follow up.

    PubMed

    Tschulakow, Alexander V; Schraermeyer, Ulrich; Rodemann, H Peter; Julien-Schraermeyer, Sylvie

    2016-11-15

    Retinoblastoma (Rb) is the most frequent primary intraocular tumour in children and, if left untreated, can cause death. Preclinical animal models that mimic molecular, genetic, and cellular features of cancers are essential for studying cancer and searching for promising diagnosis and treatment modalities. There are several models described for Rb, but none of them fully meet our requirements. The aim of this study was to create a novel xenograft-nude mouse-model with broad application possibilities, which closely resembles the clinical observations of Rb patients and which could be used to investigate the development and spread of the tumour by using scanning laser ophthalmoscopy/optical coherence tomography (SLO/OCT) as well as histology methods. We injected human retinoblastoma Y79 cells intravitreally in both eyes of immune-deficient nude mice. The incidences of retinoblastoma as well as growth velocity were analysed 3, 6, 9 and 12 weeks after cell injection in vivo by SLO/OCT as well as ex vivo by electron microscopy (EM) and hematoxylin/eosin (HE) staining. Moreover, internal organs were histologically screened for potentially occurring metastases. Three weeks post-injection, animals developed a retinoblastoma, and after five weeks tumour growth resulted in swelling of the eyes in individual animals, showing a similar phenotype to that of untreated Rb patients at advanced stages of tumour-development. After 12 weeks, 67.5% of all analysed eyes (29 of 42) contained a retinoblastoma. At early stages of Rb development, the SLO/OCT analysis correlated with the histology results. If the tumours were too large, only histological investigations were feasible. The ultrastructural characteristics of the xenograft-tumours were very similar to those described for patient's tumours. In one mouse, brain metastases were observed. Our retinoblastoma mouse model closely resembles the human disease. SLO/OCT can be used for the detection of Rb at early stages of

  8. Association of Repeated Intravitreous Bevacizumab Injections With Risk for Glaucoma Surgery.

    PubMed

    Eadie, Brennan D; Etminan, Mahyar; Carleton, Bruce C; Maberley, David A; Mikelberg, Frederick S

    2017-04-01

    Intravitreous injections of anti-vascular endothelial growth factor (VEGF) agents are associated with a sustained increase in intraocular pressure. This sustained elevated intraocular pressure could lead to higher rates of glaucoma surgery to lower this pressure. To determine the risk of glaucoma surgery following repeated intravitreous bevacizumab injections. This nested, case-control study acquired and analyzed data from large, population-based, linked health databases supported by the British Columbia Ministry of Health in Canada. Study participants included all patients with ophthalmic issues in British Columbia, such as those of the Provincial Retinal Diseases Treatment Program, who had received intravitreous bevacizumab injections for exudative age-related macular degeneration between January 1, 2009, and December 31, 2013. Cases were identified using glaucoma surgical codes for trabeculectomy, complicated trabeculectomy, glaucoma drainage device, and cycloablative procedure. For each case, 10 controls were identified and matched for age, preexisting glaucoma, calendar time, and follow-up time. The number of intravitreous bevacizumab injections received per year-3 or fewer, 4 to 6, or 7 or more-was determined for both cases and controls. Data analysis was performed from February 23, 2016, to November 14, 2016. Risk of glaucoma surgery compared with the number of intravitreous bevacizumab injections per year in cases and controls. Rate ratios were adjusted for covariates (diabetes mellitus, myocardial infarction, stroke, and verteporfin use). Seventy-four cases of glaucoma surgery and 740 controls were identified, with a mean (SD) age of 81.3 (8.4) years for cases and 81.4 (7.9) for controls. The case group had more males than the control group (38 [51.4%] vs 272 [36.8%]). The adjusted rate ratio of glaucoma surgery among those who received 7 or more injections per year was 2.48 (95% CI, 1.25-4.93). There was a 10.3% higher number of 7 or more injections among

  9. Evaluation of compounded bevacizumab prepared for intravitreal injection.

    PubMed

    Yannuzzi, Nicolas A; Klufas, Michael A; Quach, Lucy; Beatty, Lauren M; Kaminsky, Stephen M; Crystal, Ronald G; D'Amico, Donald J; Kiss, Szilárd

    2015-01-01

    Bevacizumab acquired from compounding pharmacies for intravitreal injection may cause infectious and noninfectious inflammation. In addition to safety issues, the drug itself may have variable efficacy associated with product aliquoting, handling, and distribution. To conduct surveillance cultures, evaluate endotoxin levels, and assess protein concentrations of bevacizumab obtained from compounding pharmacies in the United States. Prospective in vitro study of syringes containing intravitreal preparations of bevacizumab from compounding pharmacies. This study was conducted at a university-based, good manufacturing practice facility and academic ophthalmology practice. Microbial culture growth, endotoxin levels, and quantity and binding affinity of protein in each sample. There were no microbial contaminants or endotoxin detected in any of the samples. Of the 21 compounded samples of bevacizumab obtained from 11 pharmacies, 17 (81%) had lower protein concentrations (mean [SD], 22.2 [4.9] mg/mL; range, 19.2-24.5 mg/mL) compared with bevacizumab acquired directly from Genentech (25 mg/mL; P < .05). In 3 of 10 compounding pharmacies where more than 1 sample was available, there were statistically significant differences in the protein concentration between samples from the same compounding pharmacy. Test results from intravitreal preparations of bevacizumab acquired from compounding pharmacies were negative for microbial contaminants and endotoxin. However, there were significant variations in protein concentration that appear in general to be lower than bevacizumab acquired directly from Genentech. The clinical implications of these variable protein levels remain uncertain.

  10. Pharmacokinetics of Intravitreally Injected Bevacizumab in Vitrectomized Eyes

    PubMed Central

    Ahn, Jeeyun; Kim, Hyuncheol; Park, Ji Hyun; Park, Sunyoung; Hwang, Duck Jin; Park, Kyu Hyung

    2013-01-01

    Abstract Purpose To compare the pharmacokinetics (PKs) of intravitreally injected bevacizumab in vitrectomized versus nonvitrectomized control rabbit eyes. Methods Twenty-five-gauge pars plana vitrectomy without lensectomy was performed in 17 right rabbit eyes (V) and 18 nonvitrectomized right rabbit eyes served as controls (C). After 1.25 mg/0.05 mL intravitreal bevacizumab (IVB) injections, eyes were enucleated at 1 h, 1, 2, 5, 14, and 30 days after the injection and immediately frozen at −80°C. Bevacizumab concentrations were determined after separation of frozen vitreous and aqueous humor (AH) compartments using indirect enzyme-linked immunosorbent assay. Bevacizumab concentration–time data were analyzed to obtain PK data. Results Vitreous clearance of IVB consisted of 2 phases, the first fast distribution and second slow elimination phase. Clearance of IVB was accelerated in V eyes only during the first phase and not in the second phase. The vitreous concentration percent ratios between V and C eyes were 94.7% (1 h), 70.5% (1 day), 89.2% (2 days), 94.2% (5 days), 99.2% (14 days), and 79.1% (30 days). Overall vitreous half-lives were 6.99 and 7.06 days for V and C eyes, respectively (1.6-h difference). Conclusion Overall IVB PKs in rabbit eyes after vitrectomy without lensectomy are not substantially different from nonvitrectomized control eyes. PMID:23735192

  11. Three intravitreal bevacizumab versus two intravitreal triamcinolone injections in recent onset central retinal vein occlusion.

    PubMed

    Ramezani, Alireza; Esfandiari, Hamed; Entezari, Morteza; Moradian, Siamak; Soheilian, Masoud; Dehsarvi, Babak; Yaseri, Mehdi

    2014-11-01

    To evaluate the effects of repeated intravitreal injections of bevacizumab (IVB) versus triamcinolone acetonide (IVT) in the treatment of acute central retinal vein occlusion (CRVO). In this randomized clinical trial, 86 eyes with recent onset (<12 weeks) CRVO were assigned to two groups: IVB group (43 eyes) that received three monthly injections of 1.25 mg of IVB, and IVT group (43 eyes) that received two injections of 2 mg IVT 2 months apart. Outcomes were best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) changes. Mean BCVA improved significantly at 6 months in both groups; from 0.87 ± 0.49 to 0.41 ± 0.35 logMAR in IVB group, and from 0.81 ± 0.45 to 0.62 ± 0.48 logMAR in IVT group (p < 0.001). However, between-group differences reach a significant level at months 4 (p = 0.003) and 6 (p < 0.001) in favour of the IVB group. In terms of CMT reduction, the difference between the groups was statistically significant (p = 0.002) at month 6. Significant differences were noted more in the ischaemic cases in favour of the IVB group. Mean IOP rise was significantly higher in the IVT group at all visits. Both 3-times monthly IVB injections and 2-times IVT injections could be effective in cases with recent onset CRVO up to 6 months. However, considering the better outcomes after IVB injections and the potential complications of IVT injections, we would recommend prescheduled repeated IVB injections for such cases. The observed favourable responses were more pronounced in the ischaemic types; nevertheless, this should be confirmed in larger studies. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  12. Establishment of a novel retinoblastoma (Rb) nude mouse model by intravitreal injection of human Rb Y79 cells – comparison of in vivo analysis versus histological follow up

    PubMed Central

    Tschulakow, Alexander V.; Schraermeyer, Ulrich; Rodemann, H. Peter

    2016-01-01

    ABSTRACT Retinoblastoma (Rb) is the most frequent primary intraocular tumour in children and, if left untreated, can cause death. Preclinical animal models that mimic molecular, genetic, and cellular features of cancers are essential for studying cancer and searching for promising diagnosis and treatment modalities. There are several models described for Rb, but none of them fully meet our requirements. The aim of this study was to create a novel xenograft-nude mouse-model with broad application possibilities, which closely resembles the clinical observations of Rb patients and which could be used to investigate the development and spread of the tumour by using scanning laser ophthalmoscopy/optical coherence tomography (SLO/OCT) as well as histology methods. We injected human retinoblastoma Y79 cells intravitreally in both eyes of immune-deficient nude mice. The incidences of retinoblastoma as well as growth velocity were analysed 3, 6, 9 and 12 weeks after cell injection in vivo by SLO/OCT as well as ex vivo by electron microscopy (EM) and hematoxylin/eosin (HE) staining. Moreover, internal organs were histologically screened for potentially occurring metastases. Three weeks post-injection, animals developed a retinoblastoma, and after five weeks tumour growth resulted in swelling of the eyes in individual animals, showing a similar phenotype to that of untreated Rb patients at advanced stages of tumour-development. After 12 weeks, 67.5% of all analysed eyes (29 of 42) contained a retinoblastoma. At early stages of Rb development, the SLO/OCT analysis correlated with the histology results. If the tumours were too large, only histological investigations were feasible. The ultrastructural characteristics of the xenograft-tumours were very similar to those described for patient's tumours. In one mouse, brain metastases were observed. Our retinoblastoma mouse model closely resembles the human disease. SLO/OCT can be used for the detection of Rb at early stages of

  13. Patients’ tolerance of bimanual lid retraction versus a metal speculum for intravitreal injections

    PubMed Central

    Alattas, Khadijah

    2016-01-01

    Objective To compare patients’ acceptance of and correlate their pain level for bimanual versus metal speculum fixation in intravitreal injections. Design Prospective analysis. Participants Seventy-three eyes of 56 patients. Methods A questionnaire indicating patients’ discomfort and pain grading immediately after intravitreal injections using either bimanual fixation or metal speculum fixation (Barraquer Wire Speculum). Results Fifty-six patients who underwent intravitreal injections were enrolled in this study for various conditions. Patients’ overall pain and discomfort were as follows, right eye – bimanual was 0.3 on our grading scale with a standard deviation of 0.54, right eye – metal was 1.6 on our grading scale with a standard deviation of 1.5, left eye – bimanual was 0.41 on our grading scale with a standard deviation of 0.87, and left eye – metal was 1.91 on our grading scale with a standard deviation of 1.14 (P=0.003). Conclusion Patients who underwent bimanual fixation had a much more comfortable experience with less pain in comparison to patients who underwent metal speculum fixation. PMID:27660408

  14. Predictive factors for functional improvement following intravitreal bevacizumab injections after central retinal vein occlusion.

    PubMed

    Januschowski, Kai; Feltgen, Nicolas; Pielen, Amelie; Spitzer, Bernhard; Rehak, Matus; Spital, Georg; Dimopoulos, Spyridon; Meyer, Carsten H; Szurman, Gesine B

    2017-03-01

    Vision loss in central retinal vein occlusion (CRVO) is mostly caused by macular edema (ME) and can be treated with intravitreal bevacizumab injections. The goal of this study was to identify predictive factors for improvement in visual acuity. Three hundred and sixteen eyes of six centres having received intravitreal bevacizumab for ME due to CRVO were enrolled in this multicentre, retrospective, interventional case series. The follow-up time was 24 to 48 weeks. Investigated patient characteristics were pretreatment, duration of CRVO prior to the first injection, initial best-corrected visual acuity (BCVA), baseline central retinal thickness as measured by optical coherence tomography, gender, eye, age, comorbidity with glaucoma, systemic hypertension, or diabetes mellitus. Multiple regression analysis confirmed the following baseline predictive factors for an increase in visual acuity: low BCVA (p < 0.001), high CRT (p < 0.02), and treatment naïve patients (p = 0.03). None of the other investigated patient characteristics could be identified as prognostic factors for increase in visual acuity (p > 0.1). Intravitreal injections of bevacizumab in a routine clinical setting effectively improved and stabilized BCVA in CRVO. Our large multicenter study identified initial BCVA, baseline CRT, and pre-treatment as prognostic factors for visual improvement.

  15. Effect of ketorolac 0.5% drops on patients' pain perception during intravitreal injection procedure.

    PubMed

    Georgakopoulos, Constantine D; Vasilakis, Panagiotis T; Makri, Olga E; Beredima, Eleni; Pharmakakis, Nikolaos M

    2012-10-01

    To evaluate the analgesic effect of ketorolac 0.5% drops during the intravitreal injection procedure. Thirty patients (n=30) received topical ketorolac 0.5% or vehicle on subsequent intravitreal drug administrations. The procedure followed for the intravitreal injections was the same for all subsequent administrations with the use of tetracaine 0.5% drops as anesthetic. Ketorolac or vehicle was instilled before the injection, and pain perception was recorded on a 0 to 100 Visual Analog Scale (VAS) immediately after the intravitreal administration. Mean VAS pain score was 8.16±1.3 when patients received ketorolac and 12.33±1.41 when they received placebo, a difference that was statistically significant (P=0.0003) (paired t-test). Topical ketorolac 0.5% reduces patients' pain perception during intravitreal drug administration.

  16. Phacoemulsification with intravitreal bevacizumab injection in diabetic patients with macular edema and cataract.

    PubMed

    Akinci, Arsen; Batman, Cosar; Ozkilic, Ersel; Altinsoy, Ali

    2009-01-01

    The purpose of this study was to evaluate the results of phacoemulsification with intravitreal bevacizumab injection in patients with diabetic clinically significant macular edema and cataract. The records of 31 patients with diabetic clinically significant macular edema and cataract, which would interfere with macular laser photocoagulation, who have undergone phacoemulsification with intravitreal injection of 1.25 mg bevacizumab were retrospectively evaluated. All patients had undergone focal or modified grid laser photocoagulation 1 month after the surgery. All patients were evaluated by spectral optical coherence tomography/optical coherence tomography SLO before and 1 and 3 months after the surgery beyond complete ophthalmologic examination. The best-corrected visual acuity (BCVA) levels and central macular thickness (CMT) recorded at the first and third months after the surgery were compared with the initial values. Paired samples t test was used for statistical analysis. The mean initial BCVA was 0.10 +/- 0.04 (range, 0.05-0.2). The mean BCVA at the first and third months after the surgery were 0.47 +/- 0.16 (standard deviation) (range, 0.2-0.5) and 0.51 +/- 0.12 (standard deviation) (range, 0.3-0.6), respectively. The BCVA level recorded at the first and third months after the surgery were significantly higher than the initial BCVA (P = 0.004). The mean initial CMT was 387.5 +/- 109.5 microm. The mean CMT at the first and third months after the surgery were 292.7 +/- 57.2 and 275.5 +/- 40.3. The CMT recorded at the first and third months after the surgery were significantly lower than the initial CMT (P < 0.001, P < 0.001). Phacoemulsification with intravitreal injection of bevacizumab provides improvement in clinically significant macular edema with a gain in BCVA in patients with diabetes with clinically significant macular edema and cataract.

  17. Sterile Inflammation after Intravitreal Injection of Aflibercept in a Korean Population

    PubMed Central

    Kim, Ju Young; You, Yong Sung; Kwon, Oh Woong

    2015-01-01

    Purpose To report the frequency and clinical features of sterile inflammation after intravitreal aflibercept injection in a Korean population. Methods A single-center, retrospective study was performed in patients who received intravitreal aflibercept from July 2013 through January 2015. Results A total of four cases of post-injection sterile inflammation were identified from 723 aflibercept injections in 233 patients. Patients presented 1 to 13 days after intravitreal aflibercept injection (mean, 5 days). The mean baseline visual acuity was 20 / 60, which decreased to 20 / 112 at diagnosis but ultimately recovered to 20 / 60. Three cases had inflammatory cells in the anterior chamber (mean, 2.25+; range, 0 to 4+), and all cases had vitritis (mean, 3+; range, 2+ to 4+). No patients had pain. Only one patient underwent anterior chamber sampling (culture negative) and injection of antibiotics. Three of four patients were treated with a topical steroid, and all experienced improvement in their symptoms and signs of inflammation. Conclusions The overall incidence of sterile inflammation after intravitreal aflibercept injection in a Korean population was 4 of 723 injections (0.55%), or 4 of 233 patients (1.79%). Sterile inflammation after intravitreal aflibercept injection typically presents without pain, and the visual outcomes are generally favorable. PMID:26457038

  18. Occurrence of intraocular air bubbles during intravitreal injections for retinopathy of prematurity.

    PubMed

    Sukgen, Emine Alyamac; Gunay, Murat; Kocluk, Yusuf

    2017-02-01

    This study aims to present five cases with retinopathy of prematurity (ROP) who were found to have intraocular air bubbles after intravitreal injection (IVI) treatment. The medical records of 148 infants who underwent IVI for ROP were retrospectively reviewed and the ones who demonstrated post-injection intraocular air bubble formation were recruited. Of the 148 patients (31 babies received ranibizumab, 20 babies received aflibercept, 97 babies received bevacizumab), five were found to have intraocular air bubbles right after the IVI. Two infants received intravitreal ranibizumab and three received intravitreal bevacizumab injections. Although intraocular pressure increased temporarily, no intraocular sterile or infective reactions were observed in the postoperative period. The air bubble was found to resorb spontaneously within 72 h. The occurrence rate of the intravitreal air bubbles in our series was 3.37 % despite previously not been reported in the literature. Due to the intravitreal air injection risk, it is important to be more careful while preparing the intravitreal medication before treatment in premature babies.

  19. Bevacizumab clearance through the iridocorneal angle following intravitreal injection in a rat model.

    PubMed

    Gal-Or, Orly; Dotan, Assaf; Dachbash, Mor; Tal, Kfir; Nisgav, Yael; Weinberger, Dov; Ehrlich, Rita; Livnat, Tami

    2016-04-01

    Antivascular endothelial growth factor (Anti-VEGF) agents have been widely used for a variety of ocular disorders. The etiology of sustained ocular hypertension following intravitreal administration of anti-VEGF agents is yet to be unraveled. Our study investigates and characterizes the presence of intravitreally injected bevacizumab in the aqueous outflow channels of a rat model. Choroidal neovascularization (CNV) was induced by diode laser photocoagulation to the right eye of twelve Brown Norway rats. Bevacizumab (25 mg/ml) was injected intravitreally after 3 days. Immediately after bevacizumab injection, and 3, 6, 24 and 48 h later, animals were euthanized for immunofluorescence staining. Donkey anti-human IgG labeled with Alexa Fluor(®) 488 was used for bevacizumab immunoreactivity detection. Anti-CD31 antibody was used as a marker for Schlemm's canal endothelial cells. Untreated eyes were used as negative controls. The intensity of the immunostaining was analyzed qualitatively. Bevacizumab immunoreactivity was found in the aqueous outflow channels including the trabecular meshwork and Schlemm's canal immediately after injection, and declined incrementally within the following hours. Forty-eight hours after the injection, no bevacizumab staining was detected in the aqueous outflow channel structures. Our manuscript demonstrates the presence of bevacizumab in the trabecular meshwork and Schlemm's canal structures after intravitreal injection in a CNV induced rat model. Bevacizumab molecules passed through the aqueous outflow channels within 48 h after intravitreal bevacizumab injection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Aqueous Chlorhexidine for Intravitreal Injection Antisepsis: A Case Series and Review of the Literature.

    PubMed

    Merani, Rohan; McPherson, Zachary E; Luckie, Alan P; Gilhotra, Jagjit S; Runciman, Jim; Durkin, Shane; Muecke, James; Donaldson, Mark; Aralar, Albert; Rao, Anupam; Davies, Peter E

    2016-12-01

    To determine the incidence of endophthalmitis in a large clinical series using aqueous chlorhexidine for antisepsis before intravitreal injection and to review the ophthalmic literature regarding chlorhexidine efficacy and safety. Multicenter retrospective case series. All patients receiving intravitreal injections from 7 retinal specialists. An audit of intravitreal injections performed by retinal specialists who exclusively used aqueous chlorhexidine 0.05% or 0.1% for prophylaxis of infective endophthalmitis was undertaken. The incidence of endophthalmitis was determined from August 1, 2011, to February 28, 2015. A literature review was performed to critically appraise the ocular safety and efficacy of aqueous chlorhexidine. Incidence of endophthalmitis after intravitreal injections. A total of 40 535 intravitreal injections were performed by 7 retinal specialists across 3 centers. Chlorhexidine was well tolerated, and only 1 patient with a suspected allergic reaction was noted. Three cases of endophthalmitis were identified with 1 culture-positive case. The 0.0074% (1 in 13 512) per-injection rate of endophthalmitis in this series compares favorably with previous series in which povidone-iodine has been used. Aqueous chlorhexidine was associated with a low rate of postinjection endophthalmitis and was well tolerated by patients. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  1. Macular Hole Formation After Intravitreal Ranibizumab Injection in Wet Age-Related Macular Degeneration

    PubMed Central

    Mukherjee, Chandoshi; Mitra, Arijit; Kumar, N. Ajith; Elsherbiny, Samer; Lip, Peck Lin

    2015-01-01

    Ranibizumab is a monoclonal antibody fragment that inhibits angiogenesis by inhibiting vascular endothelial growth factor A, used as a treatment for patients with wet aged-related macular degeneration (ARMD). Adverse effects from intravitreal Ranibizumab injections are well recognised. Macular hole formation following Ranibizumab injection is a complication that has been recently reported in few case reports. We present a larger case series of five patients, who developed full thickness macular holes (FTMH) after intravitreal Ranibizumab injections for treatment of wet ARMD that we were aware of between 2009 and 2013. PMID:26962382

  2. Characteristics of Macular Edema in Behcet Disease after Intravitreal Bevacizumab Injection

    PubMed Central

    Ghassemi, Fariba; Mirak, Sohrab Afshari; Chams, Hormoz; Sabour, Siamak; Ahmadabadi, Mehdi Nilli; Davatchi, Fereidoun; Shahram, Farhad

    2017-01-01

    Purpose: To investigate the effect of intravitreal bevacizumab (IVB) injection on macular edema (ME) secondary to Behcet's disease. Methods: This prospective case series included 15 patients with bilateral ME due to Behcet's disease. Intravitreal bevacizumab was injected into the more severely involved eye; the contralateral eye was evaluated as the control. Patients were followed up with comprehensive ocular examination, optical coherence tomography, and fluorescein angiography (FA) for a minimum of 6 months by a single ophthalmologist. Results: Patients with a mean age of 30.6 ± 7.4 years received a mean number of 3.3 IVB injections during the 6 months. The mean preinjection vision was 0.6 ± 0.3 and 0.4 ± 0.4 LogMAR in the case and control groups, respectively, with no significant improvement at 6 months. Mean central foveal thickness was 375.3 ± 132.1 and 307.2 ± 84.5 μm in the case and control groups, respectively, and these changed to 401 ± 199.9 (P = 0.65) and 307.7 ± 82.8 μm (P = 0.73) at month 6, respectively. A statistically nonsignificant improvement in ME was observed during the first 3 months in the case group. However, it did not persist up to month 6 on an as-needed basis. IVB injections caused a disproportionate decrease in the thickness of macular subfields. A reduction in disc leakage was observed on FA (P = 0.058). Logistic regression analysis revealed no statistically significant predictive factor for an improvement in visual acuity (VA) and a reduction in foveal thickness. Conclusion: During a 6-month period, IVB injections based on an as-needed protocol provided no statistically significant improvement in VA and ME. PMID:28299006

  3. [The results of wet AMD treatment by intravitreal injections--preliminary report].

    PubMed

    Okruszko, Anna; Borucka, Anna I; Ulińska, Magdalena; Szaflik, Jerzy

    2007-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible, severe loss of vision in the developed countries. One of the modern methods of treatment in neovascular form of AMD are repeated intravitreal injections of ranibizumab (Lucentis). Ranibizumab is a recombinant, humanized, monoclonal antibody that neutralizes all biologically active forms of vascular endothelial growth factor A (VEGF-A). The aim of the study was to analyze the results of intravitreal ranibizumab injections in wet AMD patients. There were 57 patients enrolled in the study. 87% of them avoided any loss of visual acuity and 47.3% gained at least one line at visual acuity chart. Authors conclude that treatment with repeated intravitreal injections of ranibizumab is effective in neovascular form of AMD.

  4. Testing toxicity of multiple intravitreal injections of bevacizumab in rabbit eyes.

    PubMed

    Xu, Weiqi; Wang, Hong; Wang, Fenghua; Jiang, Yuan; Zhang, Xian; Wang, Wenqiu; Qian, Jin; Xu, Xun; Sun, Xiaodong

    2010-08-01

    To evaluate the potential toxicity of repeated intravitreal injections of bevacizumab in rabbit eyes. Randomized, placebo-controlled experimental animal study. Fourteen chinchilla rabbits; 12 assigned to the experimental group and 2 assigned to the normal control group. Three sequential, biweekly, intravitreal injections of bevacizumab in doses of 2.5 mg/0.1 mL or 5.0 mg/0.2 mL were performed on each rabbit. Evaluations included intraocular pressure (IOP), aqueous flare, B-scan ultrasound, fundus photography, ultrasound biomicroscopy, electroretinography (ERG), and visually evoked potentials (VEPs) performed at baseline and during the follow-up period. The eyes were enucleated at 1 week and 4 weeks after the last intravitreal injection, and underwent light and electron microscopic evaluations, as well as testing for apoptotic activity. After intravitreal injections, no changes were found by regular clinical observation and IOP tests. There was no significant difference in the anterior chamber inflammatory activity evaluated by the laser flare meter. No evidence of retinal toxicity was seen after intravitreal bevacizumab at doses of 2.5 and 5.0 mg by either ERG or flash VEPs. Electron microscopy did show the presence of inflammatory cells and some ultrastructural changes in the photoreceptor cells in the 5.0 mg experimental group 1 week after the third injection. Mild to moderate apoptosis of photoreceptors was detected in the 5.0 mg group at the same time. The biweekly, multiple intravitreal injections of bevacizumab did not result in evidence of toxicity in regular clinical and functional observations at both 2.5 mg and 5.0 mg doses. The 5.0 mg dose may induce transient inflammation, ultrastructural abnormalities, and apoptosis.

  5. Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits.

    PubMed

    Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

    2014-01-01

    Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery.

  6. Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits

    PubMed Central

    Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

    2014-01-01

    Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery. PMID:25028546

  7. Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide

    PubMed Central

    Smit-McBride, Zeljka; Moisseiev, Elad; Modjtahedi, Sara P.; Telander, David G.; Hjelmeland, Leonard M.; Morse, Lawrence S.

    2016-01-01

    Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in “Circadian Rhythm Signaling” pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in “Calcium Signaling” (1 week) and “Glutamate Receptor Signaling” pathways (1 month). In contrast, dexamethasone (Dex) affected the “GABA Receptor Signaling” (1 week) and “Serotonin Receptor Signaling” (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina. PMID:27429799

  8. Intravitreal injection of bevacizumab: changes in intraocular pressure related to ocular axial length.

    PubMed

    Cacciamani, Andrea; Oddone, Francesco; Parravano, Mariacristina; Scarinci, Fabio; Di Nicola, Marta; Lofoco, Giorgio

    2013-01-01

    To evaluate the immediate and short-term effects of intravitreal injection of 1.25 mg/0.05 ml of bevacizumab on intraocular pressure related to different ocular axial lengths. A prospective case series of consecutive patients referred to the Department of Ophthalmology, San Pietro-Fatebenefratelli Hospital, from September 2011 through January 2011. Twenty-five patients (10 men and 15 women, mean age 70.2 ± 8.98 years) scheduled for intravitreal injection of bevacizumab for the treatment of neovascular age-related macular degeneration were enrolled in this study. Axial length was measured preoperatively using IOLMaster. Intraocular pressure was measured before injection, after 1 min and after 15 min using Tono-Pen XL tonometry. The mean intraocular pressure change following the intravitreal bevacizumab injection was 21.92 ± 6.95 mmHg after 1 min and 6.24 ± 3.77 mmHg after 15 min. The mean axial length of the examined eyes was 23.2 ± 1.06 mm. A good correlation was observed between the axial length and intraocular pressure rise after both 1 (R (2) = 0.752, p < 0.001) and 15 min (R (2) = 0.559, p < 0.001). Patients undergoing intravitreal injection of 0.05 ml of bevacizumab can be exposed to intraocular pressure increases correlated to ocular axial length.

  9. Dramatic resolution of vitreous hemorrhage after an intravitreal injection of dobesilate.

    PubMed

    Cuevas, Pedro; Outeiriño, Luis Antonio; Azanza, Carlos; Angulo, Javier; Giménez-Gallego, Guillermo

    2015-01-01

    Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.

  10. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature.

    PubMed

    Polizzi, Silvio; Mahajan, Vinit B

    2015-12-01

    The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-VEGF," "intravitreal injection," "pregnant," "pregnancy," "abortion," "miscarriage," "preeclampsia," "embryo-fetal toxicity," "fetal malformations," "teratogenesis," "adverse events," and "maternofetal complications" in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients.

  11. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature

    PubMed Central

    Mahajan, Vinit B.

    2015-01-01

    Abstract The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms “pegaptanib,” “bevacizumab,” “ranibizumab,” “aflibercept,” “anti-VEGF,” “intravitreal injection,” “pregnant,” “pregnancy,” “abortion,” “miscarriage,” “preeclampsia,” “embryo–fetal toxicity,” “fetal malformations,” “teratogenesis,” “adverse events,” and “maternofetal complications” in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients. PMID:26302032

  12. Pharmacokinetics, Electrophysiological, and Morphological Effects of the Intravitreal Injection of Mycophenolic Acid in Rabbits

    PubMed Central

    Gasparin, Fabio; Aguiar, Renata Genaro; Ioshimoto, Gabriela Lourençon; Silva-Cunha, Armando; Fialho, Silvia Ligório; Liber, André Mauricio; Nagy, Balázs Vince; Oiwa, Nestor Norio; Costa, Marcelo Fernandes; Joselevitch, Christina; Ventura, Dora Fix

    2014-01-01

    Abstract Purpose: To determine the half-life of mycophenolic acid (MPA) in the vitreous of New Zealand albino rabbits after intravitreal injection and the retinal toxicity of different doses of MPA. Methods: Ten micrograms of MPA (Roche Bioscience, Palo Alto, CA) was injected in the vitreous of 16 rabbits, animals were sacrificed at different time-points, and vitreous samples underwent high-performance liquid chromatography. For functional and morphological studies, 5 doses of MPA (0.05, 0.5, 2, 10, and 100 μg) were injected in the vitreous of 20 rabbits. As control, contralateral eyes were injected with aqueous vehicle. Electroretinograms (ERGs) were recorded before injection and at days 7, 15, and 30. Animals were sacrificed on day 30 and retinas were analyzed under light microscopy. Results: MPA half-life in the vitreous was 5.0±0.3 days. ERG revealed photoreceptor functional impairment in eyes injected with 0.5 μg and higher on day 30, while eyes injected with 100 μg presented the same changes already from day 15. No morphological change was found. Conclusions: MPA vitreous half-life is 5.0 days. Intravitreal injection of 0.5 μg MPA and higher causes dose- and time-related photoreceptor sensitivity decrease in rabbits. The MPA dose of 0.05 μg may be safe for intravitreal use in rabbits. PMID:24828287

  13. The role of topical antibiotic prophylaxis to prevent endophthalmitis after intravitreal injection.

    PubMed

    Storey, Philip; Dollin, Michael; Pitcher, John; Reddy, Sahitya; Vojtko, Joseph; Vander, James; Hsu, Jason; Garg, Sunir J

    2014-01-01

    To compare the incidence of endophthalmitis after intravitreal injection with and without topical postinjection antibiotic prophylaxis. Retrospective case-control study. All patients treated with intravitreal injection of ranibizumab, bevacizumab, or aflibercept for a variety of retinal vascular diseases at a single, large retina practice between January 1, 2009, and October 1, 2012, were included. The total numbers of patients and injections were determined from a review of billing code and practice management records. Endophthalmitis cases were determined from billing records and from an infection log. All cases of endophthalmitis were confirmed with chart review. A 28-month period when topical antibiotics were prescribed after intravitreal injection was compared with a 9-month period when topical antibiotics were not prescribed. Patients treated during an 8-month transition period were excluded to allow for the conversion of antibiotic prescription practices. Incidence of endophthalmitis, visual acuity outcomes, and microbial spectrum. During the study period, a total of 117 171 intravitreal injections were performed (57 654 injections during the topical antibiotic period, 24 617 during the transition period, and 34 900 during the no-antibiotic period), with a total of 44 cases of suspected endophthalmitis (0.038%; 1 in 2663 injections), 17 of which showed culture-positive results (0.015%; 1 in 6892 injections). During the 28-month topical antibiotic period, there were 28 cases of suspected endophthalmitis (0.049%; 1 in 2059 injections), 10 of which showed culture-positive results (0.017%; 1 in 5765 injections). During the 9-month no-antibiotic period, there were 11 cases of suspected endophthalmitis (0.032%; 1 in 3173 injections), 4 of which showed culture-positive results (0.011%; 1 in 8725 injections). Topical antibiotic use was associated with a trend toward increased risk of suspected endophthalmitis (odds ratio [OR], 1.54; 95% confidence interval

  14. Quantitative evaluation of reduction of plaque-like hard exudates in diabetic macular edema after intravitreal triamcinolone injection.

    PubMed

    Cekiç, Osman; Bardak, Yavuz; Tiğ, U Sahin; Yildizoğlu, Uzeyir; Bardak, Handan

    2008-04-01

    To describe a new method of quantifying the amount of plaque-like hard exudates after intravitreal triamcinolone acetonide injection in diabetic macular edema. This study included 22 eyes of 14 patients (mean age, 63 years) with chronic diabetic macular edema and plaque-like hard exudates. The patients were injected with a single dose of 4 mg intravitreal triamcinolone acetonide. The optic disc size as relative size unit was taken to quantify the hard exudates: Total areas of exudates and the optic nerve head were computed from fundus pictures with a digital analysis program on magnified images. The former was divided by the latter, and the results were expressed as a percentage value. The ratio was used to track improvements in a given eye over 6 months. Average ratio of hard exudates to optic nerve head area reduced to 81% of its initial value at 1 month (P=0.007), to 54% at 3 months (P<0.001) and to 41% at 6 months (P<0.001). The new method allowed detection of a significant reduction of ratio of hard exudates to optic disc area of diabetic plaque-like hard exudates following 4 mg intravitreal triamcinolone.

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

    PubMed Central

    Ye, Zhuo; Ji, Yan-Li; Ma, Xiang; Wen, Jian-Guo; Wei, Wei; Huang, Shu-Man

    2015-01-01

    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/hO) 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 days 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 that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d 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-t of 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 42d. It was longer than that of the soluble form. CONCLUSION The result of this study

  16. The effect of prophylactic topical antibiotics on bacterial resistance patterns in endophthalmitis following intravitreal injection.

    PubMed

    Storey, Philip; Dollin, Michael; Rayess, Nadim; Pitcher, John; Reddy, Sahitya; Vander, James; Hsu, Jason; Garg, Sunir

    2016-02-01

    The purpose of this study was to evaluate the effect of prophylactic topical antibiotics on bacterial resistance patterns in endophthalmitis following intravitreal injection of anti-vascular endothelial growth factor (VEGF) medications. In this retrospective case-control study, billing records and an infection log were used to identify all cases of endophthalmitis following intravitreal injection of ranibizumab, bevacizumab, or aflibercept between January 1, 2009 and September 30, 2013 at a single retina practice. A 28-month period when topical antibiotic drops were prescribed for use four times a day for 4 days following intravitreal injection was compared to a 21-month period when topical antibiotics were not prescribed. Patients treated during an 8-month transition period were excluded as prescription practices were changed. During the study period, a total of 172,096 anti-VEGF injections were performed. During the period when antibiotics were prescribed, 28 cases of suspected infectious endophthalmitis occurred from a total of 57,654 injections, ten of which were culture-positive. During the period when antibiotics were not used, 24 cases of suspected endophthalmitis occurred from a total of 89,825 injections, six of which were culture-positive. During the antibiotic period, four of the ten (40 %) culture-positive cases grew bacteria resistant to the prescribed prophylactic antibiotics. In contrast, none of the six culture-positive cases grew bacteria resistant to those antibiotics during the period when antibiotics were not used (odds ratio = 9.0; 95 % confidence interval = 0.40-203.3; p = 0.17). The use of prophylactic topical antibiotics following intravitreal injection may lead to higher rates of antibiotic-resistant bacteria in culture-positive endophthalmitis cases.

  17. Micropulsed laser photocoagulation and intravitreal triamcinolone acetonide injection for the treatment of retinal angiomatous proliferation.

    PubMed

    Roth, Daniel B; Scott, Ingrid U; Gloth, Jonathan M; Green, Stuart N; Yarian, David L; Wheatley, Matthew

    2007-01-01

    To investigate visual acuity and fluorescein angiographic outcomes, as well as adverse events, associated with treatment of retinal angiomatous proliferation (RAP) with micropulsed laser photocoagulation and intravitreal triamcinolone acetonide injection. In this retrospective, noncomparative, interventional, consecutive case series, the medical records of all patients treated for RAP with micropulsed laser photocoagulation (yellow or green dye; duration, 0.02-0.05 second; power adjusted to achieve a white burn of moderate intensity at the level of the RAP lesion in the retina) and intravitreal triamcinolone acetonide (4 mg/0.1 mL) injection between January 2003 and November 2004 were reviewed by one of four retina specialists at a single retina practice. Main outcome measures were visual acuity, leakage shown by fluorescein angiography, and adverse events. The study included 14 eyes of 13 patients (8 women and 5 men; median age, 83 years [range, 70-90 years]). Triamcinolone acetonide injection preceded laser treatment by a median duration of 7 days (range, 5-16 days) in 8 eyes, was performed on the same day as laser treatment in 2 eyes, and followed laser treatment by a median duration of 7 days (range, 7-28 days) in 4 eyes. Eyes were followed a median of 18 months (range, 12-27 months) after treatment with both laser and intravitreal triamcinolone injection. Compared with pretreatment visual acuity, vision at 12 months and the last follow-up examination was stable in 5 eyes (36%), improved by >or=2 lines in 6 eyes (43%), and worsened by >or=2 lines in 3 eyes (21%). The median visual acuity before treatment was 20/200 compared with 20/80 at 3 months after treatment (P = 0.02), 20/100 at 6 months after treatment (P = 0.16), 20/200 at 12 months after treatment (P = 0.73), and 20/100 (P = 0.63) at the last follow-up examination. For 13 eyes (93%), fluorescein angiography performed 6 months after administration of both laser and intravitreal triamcinolone injection

  18. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections.

    PubMed

    Cheung, Crystal S Y; Wong, Amanda W T; Lui, Alex; Kertes, Peter J; Devenyi, Robert G; Lam, Wai-Ching

    2012-08-01

    To report the incidence of endophthalmitis in association with different antibiotic prophylaxis strategies after intravitreal injections of anti-vascular endothelial growth factors and triamcinolone acetonide. Retrospective, comparative case series. Fifteen thousand eight hundred ninety-five intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January 5, 2005, and August 31, 2010. The number of injections was determined from billing code and patient records. The indications for injection included age-related macular degeneration, diabetic macular edema, central and branch retinal vein occlusion, and miscellaneous causes. Three strategies of topical antibiotic prophylaxis were used by the respective surgeons: (1) antibiotics given for 5 days after each injection, (2) antibiotics given immediately after each injection, and (3) no antibiotics given. The primary outcome measures were the incidence of culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis. Nine eyes of 9 patients with suspected endophthalmitis after injection were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis was 9 in 15 895. The incidence of culture-negative cases of suspected endophthalmitis and culture-proven endophthalmitis after injection was 6 in 15 895 and 3 in 15 895, respectively. Taking into account both culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis, the incidence per injection was 5 in 8259 for patients who were given antibiotics for 5 days after injection, 2 in 2370 for those who received antibiotics immediately after each injection, and 2 in 5266 who received no antibiotics. However, if considering culture-proven endophthalmitis alone, the use of topical antibiotics, given immediately or for 5 days after injection, showed lower rates of endophthalmitis

  19. Effect of betaxolol on impaired choroidal blood flow after intravitreal injection of endothelin-1 in albino rabbits.

    PubMed

    Kim, Jong Hyun; Kim, Dong Myung; Park, Won Chan

    2002-06-01

    We investigated the effect of topical betaxolol on impaired choroidal blood flow (CBF) induced by endothelin-1 (ET-1) injection into the vitreous of albino rabbits. Betaxolol (n = 7) or balanced salt solution (BSS) (n = 6) was instilled in the right eyes before and 12 hrs after the intravitreal injection of ET-1 (10(-6) M, 10 microl), and BSS was instilled in the right eyes before and 12 hrs after the intravitreal injection of BSS (n = 6). Blood pressure, intraocular pressure and CBF were measured prior to the instillation of betaxolol or BSS, and just before and 2 hrs, 12 hrs and 24 hrs after ET-1 or BSS injection. CBF was measured by scanning laser Doppler flowmetry. Intravitreal injection of ET-1 decreased CBF. Compared with topical BSS, topical betaxolol significantly inhibited the decrease in CBF at 2 hrs (p = .022), 12 hrs (p = .046) and 24 hrs (p = .015) after the intravitreal injection of ET-1. There was no significant change of blood pressure or intraocular pressure after the topical administration of betaxolol or the intravitreal injection of ET-1. The decrease in CBF after the intravitreal injection of ET-1 was partially inhibited by topical betaxolol.

  20. Selective photoreceptor degeneration by intravitreal injection of N-methyl-N-nitrosourea.

    PubMed

    Rösch, Sarah; Johnen, Sandra; Mataruga, Anja; Müller, Frank; Pfarrer, Christiane; Walter, Peter

    2014-03-20

    To characterize the effects of intravitreal injections of N-methyl-N-nitrosourea (MNU) in comparison to its systemic application as a measure of inducing unilateral photoreceptor degeneration. Eight-week-old male C57BL/6J mice received either intraperitoneal injections (three animals) or intravitreal injections (24 animals) of MNU in different concentrations and were observed over a period of 2 weeks using full-field electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and immunohistochemistry. The intraperitoneal application of MNU showed moderate systemic toxic effects, indicated by a loss of body weight of 12% within the first 2 days. In both eyes the ERG became extinguished, and SD-OCT scans showed a thinning of the retina, predominantly in the outer nuclear layer (ONL). Immunohistochemistry demonstrated the selective loss of rods and cones. Mice that received intravitreal MNU injections displayed nearly no weight loss, and no degeneration of their general welfare was observed. After 2 weeks, ERG, SD-OCT, and immunohistochemistry revealed changes identical to those seen after systemic application in the injected eye, but not in the control eye. The intraperitoneal application of MNU led to moderate systemic side effects in mice and to selective photoreceptor degeneration. Intravitreal injections of MNU also induced photoreceptor degeneration; however, no systemic side effects were observed. This tool may be helpful in larger species, where genetic models of receptor degenerations are not applicable but where the size of the eye is more suitable to study surgical or other approaches to treat blindness caused by receptor degeneration.

  1. Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes

    PubMed Central

    Dejneka, Nadine S.; Wan, Shanhong; Bond, Ottrina S.; Kornbrust, Douglas J.

    2008-01-01

    Purpose The primary objective of these investigations was to determine the ocular biodistribution of bevasiranib, a small interfering RNA (siRNA) targeting vascular endothelial growth factor A (VEGF-A), following a single intravitreal injection to rabbit eyes. Methods A tissue distribution and pharmacokinetic study was conducted with 3H-bevasiranib prepared in balanced-salt solution (BSS). Single doses of either 0.5 mg/eye or 2.0 mg/eye of 3H-bevasiranib were given by intravitreal injection to Dutch-Belted rabbits (both eyes were treated). Subgroups of rabbits were serially-sacrificed at various times up to 7 days following dosing for collection of tissue samples. The right eye of each rabbit was collected whole, and the left eye was dissected to isolate five ocular tissues. All samples were analyzed by liquid scintillation counting to determine the concentrations of bevasiranib equivalents. An ocular disposition study was also performed with non-radiolabeled bevasiranib, which was administered to Dutch-Belted rabbit eyes via intravitreal injection at a dose of 2.0 mg/eye. Twenty-four hours post-dose, the eyes were enucleated and dissected into eight individual ocular structures that were analyzed for intact bevasiranib using a locked nuleic acid (LNA) noncompetitive hybridization-ligation enzyme-linked immunosorbent assay. Results Following intravitreal injection of 0.5 mg or 2.0 mg radiolabeled bevasiranib to Dutch-Belted rabbits, bevasiranib was detected in the vitreous, iris, retina, retinal pigment epithelium (RPE), and sclera (+choroid). As expected, the highest concentrations were found in the vitreous, and vitreous levels steadily decreased over time, while concentrations of radioactivity in the other ocular tissues increased to maximum values between 24 h and 72 h after dosing. Of these tissues, the highest concentration of radioactivity was detected in the retina. The LNA assay further confirmed the presence of intact bevasiranib in these tissues 24 h

  2. Intravitreal Aflibercept Injection in Eyes With Substantial Vision Loss After Laser Photocoagulation for Diabetic Macular Edema: Subanalysis of the VISTA and VIVID Randomized Clinical Trials.

    PubMed

    Wykoff, Charles C; Marcus, Dennis M; Midena, Edoardo; Korobelnik, Jean-François; Saroj, Namrata; Gibson, Andrea; Vitti, Robert; Berliner, Alyson J; Williams Liu, Zinaria; Zeitz, Oliver; Metzig, Carola; Schmelter, Thomas; Heier, Jeffrey S

    2016-12-22

    Information on the effect of anti-vascular endothelial growth factor therapy in eyes with diabetic macular edema (DME) with vision loss after macular laser photocoagulation is clinically valuable. To evaluate visual and anatomic outcomes in a subgroup of macular laser photocoagulation treatment control (hereafter laser control) eyes with substantial vision loss receiving treatment with intravitreal aflibercept injection. This investigation was a post hoc analysis of a subgroup of laser control eyes in 2 phase 3 trials-VISTA (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) and VIVID (Intravitreal Aflibercept Injection in Vision Impairment Due to DME)-in a multicenter setting. One hundred nine laser control eyes with center-involving DME were included. Treatment with intravitreal aflibercept injection (2 mg) every 8 weeks after 5 monthly doses with sham injections on nontreatment visits starting at week 24 was initiated on meeting prespecified criteria of at least a 10-letter visual acuity loss at 2 consecutive visits or at least a 15-letter visual acuity loss from the best previous measurement at 1 visit and vision not better than at baseline. Visual and anatomic outcomes in a subgroup of laser control eyes receiving treatment with intravitreal aflibercept injection. Through week 100, a total of 63 of 154 eyes (40.9%) in VISTA and 46 of 133 eyes (34.6%) in VIVID initially randomized to laser control received treatment with intravitreal aflibercept injection. The median time from week 24 to the first intravitreal aflibercept injection treatment was 34.0 (VISTA) and 83.5 (VIVID) days. In this subgroup, the mean (SD) visual gain from baseline to week 100 was 2.2 (12.5) (VISTA) and 3.8 (10.1) (VIVID) letters. At the time of intravitreal aflibercept injection initiation, these eyes had a mean (SD) loss of 11.0 (10.1) (VISTA) and 10.0 (6.5) (VIVID) letters from baseline, and they subsequently gained a mean (SD) of 17.4 (9.7) (VISTA

  3. Resolution of Severe Macular Edema in Adult Coats' Disease with Intravitreal Triamcinolone and Bevacizumab Injection

    PubMed Central

    Jun, Jong-Hwa; Kim, Kwang-Soo

    2008-01-01

    A 47 year old male patient visited our hospital with the chief complaint of deterioration of the visual acuity in the left eye. The fundus examination revealed thick hard exudates, multiple aneurysms and telangiectasias of the retinal vessels in the posterior pole. Fluorescein angiography demonstrated massive leakage over an area of the aneurysms. Optical coherence tomography (Stratus OCT; Zeiss-Humphrey, Dubin, CA) revealed diffuse and marked thickening of the retina. Laser photocoagulation was performed under the diagnosis of Coats' disease. However, the treatment could not be performed satisfactorily. On the first and 6th weeks, an intravitreal injection of bevacizumab and triamcinolone acetonide was administered, and laser photocoagulation was again attempted. The effectiveness of eachagent on retinal edema was evaluated at the follow-up performed at 1, 2, 5, 7, 10 weeks and 6 months after the injection. At one week after the intravitreal bevacizumab injection, there was no improvement. An intravitreal injection of triamcinolone acetonide was performed 6 weeks after the initial diagnosis,which resulted in a reduction in the thickness of the macular edema. Therefore, laser photocoagulation was performed sufficiently on telangiectasias. The follow-up at 6 months showed a relative increase in the macular edema, but there was reduced leakage from the telangiectasias compared with the previous angiograph. PMID:18784449

  4. Diffuse alveolar haemorrhage may be associated with intravitreal injection of bevacizumab in a patient with systemic risk factors.

    PubMed

    Seto, Ruriko; Yamada, Hideto; Wada, Hiroshi; Osawa, Makoto; Nagao, Taishi; Nakano, Yasutaka

    2011-02-02

    The authors present a rare case where acute respiratory failure occurred after the intravitreal bevacizumab injection for a branch retinal vein occlusion. Chest CT scan showed ground-glass opacity in the bilateral lung fields. The finding of bronchoalveolar lavage fluid revealed alveolar haemorrhage. Corticosteroid therapy resulted in a rapid improvement of respiratory failure. This report suggests that intravitreal injection of bevacizumab may be associated with diffuse alveolar haemorrhage and acute lung injury.

  5. Diffuse alveolar haemorrhage may be associated with intravitreal injection of bevacizumab in a patient with systemic risk factors

    PubMed Central

    Seto, Ruriko; Yamada, Hideto; Wada, Hiroshi; Osawa, Makoto; Nagao, Taishi; Nakano, Yasutaka

    2011-01-01

    The authors present a rare case where acute respiratory failure occurred after the intravitreal bevacizumab injection for a branch retinal vein occlusion. Chest CT scan showed ground-glass opacity in the bilateral lung fields. The finding of bronchoalveolar lavage fluid revealed alveolar haemorrhage. Corticosteroid therapy resulted in a rapid improvement of respiratory failure. This report suggests that intravitreal injection of bevacizumab may be associated with diffuse alveolar haemorrhage and acute lung injury. PMID:22714606

  6. Epiretinal deposit of triamcinolone acetonide at the posterior pole after intravitreal injection.

    PubMed

    Jaissle, Gesine B; Szurman, Peter; Völker, Michael; Bartz-Schmidt, Karl Ulrich

    2007-01-01

    The authors investigated possible toxic side effects of epiretinal triamcinolone acetonide deposits at the posterior pole after an intravitreal injection in both a vitrectomized and a non-vitrectomized eye. The vitrectomized eye developed massive epiretinal triamcinolone acetonide deposits at the posterior pole that were less pronounced in the non-vitrectomized eye. After resolution of the deposits, no morphologic signs of retinal toxicity were apparent. Mild scattered visual field defects did not correlate with the localization of the triamcinolone acetonide deposits. However, because recent in vitro studies indicate potential cytotoxicity, patients should be instructed to keep their heads in an upright position after intravitreal triamcinolone acetonide injection to avoid deposits at the posterior pole.

  7. Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles.

    PubMed

    Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J; Freeman, William R; Cheng, Lingyun

    2013-11-01

    Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles

    PubMed Central

    Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2013-01-01

    Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals. PMID:24036388

  9. Strategies for Improving Patient Comfort During Intravitreal Injections: Results from a Survey-Based Study.

    PubMed

    Gomez, Jessica; Koozekanani, Dara D; Feng, Alex Z; Holt, Mitchell; Drayna, Paul; Mackley, Melissa R; van Kuijk, Frederik J G M; Beardsley, Robert M; Johnston, Richard H; Terry, Joseph M; Montezuma, Sandra R

    2016-12-01

    Many ocular diseases require intravitreal injections of pharmacological agents. Optimizing patients' experiences during injections is important to ensure compliance and maintenance of quality of life. The objective of this study was to identify strategies to help alleviate discomfort during intravitreal injections. A cross-sectional study surveying 128 patients during clinic visits between 2014 and 2015 in two outpatient Retina Clinics (one academic and one private). Patients receiving an intravitreal injection(s) for any retinal disorder were given a questionnaire with 10-yes/no responses for various potential strategies. Responses were stratified by sex, age (<30 years, 30-60 years, and >60 years) and total number of prior injections (0-9 injections, 10-20 injections and >20 injections). A total of 128 patients were surveyed: 59 males, 41 females and 28 with no sex specified. Our results identified four favorable strategies as those receiving more than 50% "yes" votes. These included the presence of technician/staff during the procedure, the use of a neck pillow, a verbal warning before the injection and performing injections in both eyes on the same day. Other specific strategies were identified for females, younger patients and those with greatest experience. These included: females preferred having their hand held during injections (P = 0.001) and using a stress ball (P = 0.000) when compared to males. Stratifying by age, patients 30-60 years old preferred having their hand held (P = 0.008) and background music (P = 0.007). Stratifying by prior injections, patients with >20 prior injections preferred having their hand held (P = 0.001), using a stress ball (P = 0.021) and, if necessary, having bilateral injections performed the same day to improve comfort (P = 0.037). Having an extra staff member present during the injection, having a neck pillow, having a verbal warning prior to injection and having both eyes injected on the same day were

  10. [Extemporaneous withdrawal with a mini-spike filter: A low infection risk technique for drawing up bevacizumab for intravitreal injection].

    PubMed

    Le Rouic, J F; Breger, D; Peronnet, P; Hermouet-Leclair, E; Alphandari, A; Pousset-Decré, C; Badat, I; Becquet, F

    2016-05-01

    To describe a technique for extemporaneously drawing up bevacizumab for intravitreal injection (IVT) and report the rate of post-injection endophthtalmitis. Retrospective monocentric analysis (January 2010-December 2014) of all IVT of bevacizumab drawn up with the following technique: in the operating room (class ISO 7) through a mini-spike with an integrated bacteria retentive air filter. The surgeon was wearing sterile gloves and a mask. The assisting nurse wore a mask. The bevacizumab vial was discarded at the end of each session. Six thousand two hundred and thirty-six bevacizumab injections were performed. One case of endophthalmitis was noted (0.016%). During the same period, 4 cases of endophthalmitis were found after IVT of other drugs (4/32,992; 0.012%. P=0.8). Intravitreal injection of bevacizumab after extemporaneous withdrawal through a mini-spike filter is a simple and safe technique. The risk of postoperative endophthalmitis is very low. This simple technique facilitates access to compounded bevacizumab. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. [Time course of changes in aqueous flare following intravitreous gas injection in rabbits].

    PubMed

    Yamamoto, K

    1991-06-01

    The quantitative changes of the aqueous flare following intravitreous gas injection were determined by laser flare-cell metry in rabbits. A volume of 0.4 ml of air, 100% sulfur hexafluoride (SF6), or 100% perfluoropropane (C3F8), was injected separately into the vitreous of pigmented rabbits. The normal range of the aqueous flare was 7.8 +/- 3.0 (photon counts/msec). Each model showed an increase of aqueous flare on the first day (air: 18.9 +/- 9.1, SF6: 19.5 +/- 11.5, C3F8: 40.8 +/- 22.8). Subsequently, the aqueous flare of air-injected eyes gradually decreased, while that of SF6-injected eyes increased on the 4th day, and then gradually decreased. Also that of C3F8-injected eyes increased on the 4th day, and the 7th day, then decreased on the 14th day, but it was still higher than normal. Cataracts developed in two of the five eyes injected with SF6 and all of the four eyes injected with C3F8. These findings revealed that following intravitreous gas injection, disruption of the blood-ocular barrier depended on the expansibility of the gas and the length of time it remained in the vitreous cavity.

  12. Ocular disposition and tolerance of ganciclovir-loaded albumin nanoparticles after intravitreal injection in rats.

    PubMed

    Merodio, Marta; Irache, Juan Manuel; Valamanesh, Fatemeh; Mirshahi, Massoud

    2002-04-01

    Cytomegalovirus (CMV) infection mainly affects endothelial cells of ocular vessels, optic nerve and the retina, resulting in direct or autoimmune damages, uveoretinitis and disturbed vision. The use of colloidal carriers for the intravitreal delivery of ganciclovir may prolong its residence in the eye, minimizing the opacification observed for macroscopic implants. The aim of this work was to evaluate the ocular toxicity induced by the prolonged presence of ganciclovir-loaded bovine serum albumin nanoparticles after their intravitreal injection. The intraocular disposition of these carriers was also studied by immunochemistry. Two weeks post-injection, a significant amount of nanoparticles remained in the vitreous cavity, mainly in a thin layer overlying the retina and in the area close to the blood aqueoUs barrier. Their prolonged residence in the eve seemed to be well tolerated and the histological evaluation of the retina, mainly the photoreceptor layer, and adjacent tissues revealed the absence of inflammatory reactions or alterations in the tissue architecture (i.e. cellular infiltrations or vascular inflammation). In addition, nanoparticles neither alter the expression and distribution of arrestin and rhodopsin autoantigens nor the mineralocorticoid receptor. In summary, the vision was not affected by autoimmune phenomena or alterations in the behavior of ophthalmic cells due to the intravitreal injection of these nanoparticles.

  13. Treatment of CNV secondary to presumed ocular histoplasmosis with intravitreal aflibercept 2.0 mg injection.

    PubMed

    Walia, Harpreet S; Shah, Gaurav K; Blinder, Kevin J

    2016-04-01

    To assess the efficacy and safety of intravitreal aflibercept injection in the treatment of CNV secondary to presumed ocular histoplasmosis syndrome (POHS). To assess safety of intravitreal aflibercept for the treatment of CNV secondary to presumed ocular histoplasmosis syndrome. Masked, open-label, prospective study. Five subjects will receive 2.0 mg aflibercept injection every 8 weeks with 3 initial monthly doses over a 12 month period. No adverse systemic or ocular were reported. At month six, the mean visual acuity improved by 7.8 ETDRS letters, mean central subfoveal thickness decreased by 38.8 microns and mean OCT volume decreased by 0.076 mm3 . At month twelve, the mean visual acuity improved by 12.4 ETDRS letters, mean central subfoveal thickness decreased by 34.6 microns and mean OCT volume decreased by 0.576 mm3. The use of intravitreal 2.0 mg aflibercept injection for the treatment of CNV secondary to presumed ocular histoplasmosis syndrome yielded no systemic or ocular adverse events and produced improvement in visual acuity and reduction of OCT thickness and volume. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  14. Intravitreal injection of ziv-aflibercept in the treatment of choroidal and retinal vascular diseases.

    PubMed

    HodjatJalali, Kamran; Mehravaran, Shiva; Faghihi, Hooshang; Hashemi, Hassan; Kazemi, Pegah; Rastad, Hadith

    2017-09-01

    To investigate the short-term outcomes after intravitreal injection of ziv-aflibercept in the treatment of choroidal and retinal vascular diseases. Thirty-four eyes of 29 patients with age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion (RVO) received a single dose intravitreal injection of 0.05 ml ziv-aflibercept (1.25 mg). Visual acuity, spectral domain optical coherence tomography (SD-OCT) activity, and possible side effects were assessed before and at 1 week and 1 month after the intervention. At 1 month after treatment, mean central macular thickness (CMT) significantly decreased from 531.09 μm to 339.5 μm (P < 0.001), and no signs of side effects were observed in any subject. All patients responded to treatment in terms of reduction in CMT. The improvement in visual acuity was statistically non-significant. Our findings suggest that a single dose intravitreal injection of ziv-aflibercept may have acceptable relative safety and efficacy in the treatment of patients with intraocular vascular disease. The trial was registered in the Iranian Registry of Clinical Trials (IRCT2015081723651N1).

  15. Microperimetric changes after intravitreal triamcinolone acetonide injection for macular edema due to central retinal vein occlusion.

    PubMed

    Senturk, Fevzi; Ozdemir, Hakan; Karacorlu, Murat; Karacorlu, Serra Arf; Uysal, Omer

    2010-09-01

    The purpose of this study was to evaluate the effect of intravitreal triamcinolone acetonide on macular function in cases of macular edema because of central retinal vein occlusion. Twelve eyes of 12 patients with central retinal vein occlusion were included in this study. In each eye, at baseline and 1, 3, and 6 months after intravitreal triamcinolone acetonide injection, logarithm of the minimum angle of resolution visual acuity, macular sensitivity, fixation stability and fixation location by MP-1 microperimetry, and foveal thickness by optical coherence tomography were assessed. Patients' ages ranged from 50 to 75 years (mean +/- SD, 59 +/- 8 years). All patients were classified as nonischemic. At 1, 3, and 6 months, the mean foveal thickness had decreased from 453 +/- 108 microm to 254 +/- 40.3 microm, 297 +/- 90 microm, and 320 +/- 82 microm and the mean retinal sensitivity had increased from 5.5 +/- 3.3 dB to 9.4 +/- 3.5 dB, 7.8 +/- 3.3 dB, and 7.2 +/- 4.2 dB, respectively. At baseline, fixation was stable in one, relatively unstable in six, and unstable in five eyes. However, 6 months after intravitreal triamcinolone acetonide injection, fixation was stable in 8, relatively unstable in 3, and unstable in one. At baseline, in eyes with macular edema, fixation location was predominantly central in 2, poor central in 4, and predominantly eccentric in 6. And 6 months after treatment, fixation location was predominantly central in 8, poor central in 3, and predominantly eccentric in 1. In eyes with macular edema in central retinal vein occlusion, a short-term improvement in retinal sensitivity and fixation properties can be achieved by intravitreal triamcinolone acetonide injection.

  16. Sustained intravitreal delivery of dexamethasone using an injectable and biodegradable thermogel.

    PubMed

    Zhang, Li; Shen, Wenjia; Luan, Jiabin; Yang, Dongxiao; Wei, Gang; Yu, Lin; Lu, Weiyue; Ding, Jiandong

    2015-09-01

    Delivery of therapeutic agents to posterior segment of the eyes is challenging due to the anatomy and physiology of ocular barriers and thus long-acting implantable formulations are much desired. In this study, a thermogelling system composed of two poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers was developed as an injectable matrix for intravitreal drug delivery. The thermogel was prepared by mixing a sol and a precipitate of PLGA-PEG-PLGA triblock copolymers with different block ratios, among which a hydrophobic glucocorticoid, dexamethasone (DEX), was incorporated. The DEX-loaded thermogel was a low-viscous liquid at low temperature and formed a non-flowing gel at body temperature. The in vitro release rate of DEX from the thermogel could be conveniently modulated by varying the mixing ratio of the two copolymers. The long-lasting intraocular residence of the thermogel was demonstrated by intravitreal injection of a fluorescence-labeled thermogel to rabbits. Compared with a DEX suspension, the intravitreal retention time of DEX increased from a dozen hours to over 1week when being loaded in the thermogel. Additionally, intravitreal administration of the thermogel did not impair the morphology of retina and cornea. This study reveals that the injectable PLGA-PEG-PLGA thermogel is a biocompatible carrier for sustained delivery of bioactive agents into the eyes, and provides an alternative approach for treatment of posterior segment diseases. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. Effect of pegaptanib sodium 0.3 mg intravitreal injections (Macugen) in intraocular pressure: posthoc analysis from V.I.S.I.O.N. study.

    PubMed

    Boyer, David S; Goldbaum, Mauro; Leys, Anita M; Starita, Carla

    2014-11-01

    To assess the rate of pegaptanib-associated sustained intraocular pressure (IOP) elevation. A posthoc analysis was conducted on all IOP measurements, except the immediate 30-min postinjection, from all subjects randomised to pegaptanib 0.3 mg or sham injections continuously in the first 2 years of the Vascular endothelial growth factor Inhibition Study in Ocular Neovascularisation (V.I.S.I.O.N.) study. Measurements were taken with Goldmann applanation tonometer or Tonopen, except at baseline and in cases of an IOP reading >30 mm Hg when a Goldmann applanation tonometer was mandatory. Of 221 subjects, IOP measurements ≥22 mm Hg were seen in 28/114 and 23/107 subjects of the pegaptanib and sham subgroups, respectively (p=0.6338) and measurements ≥24 mm Hg were observed in eight and eight subjects in the pegaptanib and sham groups, respectively. More than two measurements ≥22 mm Hg occurred in six and 10 subjects (p=0.3025), and more than two measurements ≥24 mm Hg were observed in one and four subjects in the pegaptanib and sham groups, respectively. One patient with sustained IOP elevation in the pegaptanib study group, and four in the sham group, had IOP lowering medication added during the course of the study. No subject required glaucoma surgery. In V.I.S.I.O.N., after 2 years, there was no evidence of sustained IOP elevation associated with pegaptanib 0.3 mg use. NCT00321997. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits

    PubMed Central

    Damico, Francisco Max; Scolari, Mariana Ramos; Ioshimoto, Gabriela Lourençon; Takahashi, Beatriz Sayuri; da Silva Cunha, Armando; Fialho, Sílvia Ligório; Bonci, Daniela Maria; Gasparin, Fabio; Ventura, Dora Fix

    2012-01-01

    OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision. RESULTS: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina. PMID:22948462

  19. Intravitreal injection of docosahexaenoic acid attenuated photoreceptor cell injury in a NaIO3-induced age-related macular degeneration rat model.

    PubMed

    Qiu, Suo; Wei, Yantao; Zhou, Xuezhi; Jiang, Zhaoxin; Zhang, Ting; Jiang, Xintong; Zhang, Shaochong

    2017-09-14

    In most studies, the major supplement docosahexaenoic acid (DHA) is administered orally or intraperitoneally. In this study, we proposed to assess the safety and efficacy of the intravitreal injection of DHA in an age-related macular degeneration (AMD) rat model. Different concentrations of DHA were injected into the vitreous body. Histopathology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis showed that there was no difference in thickness, observable structure, or apoptosis among the untreated, normal saline, and DHA groups (0.2, 1.0, 5.0 and 10μg). However, GFAP expression was increased in the 10μg group. To investigate whether intravitreal injection of DHA could protect photoreceptors, we developed a NaIO3-induced retinal damage model in adult rats. Decreases in deformation and thickness were observed in the outer nuclear layer (ONL) after NaIO3 administration but were improved with DHA injection. The NaIO3 group showed a substantial reduction in the number of nuclei in ONL, whereas the DHA group showed an increase. Additionally, significant increases in SOD activity and Nrf2 expression were observed after DHA injection; GFAP and NF-κB expression levels were markedly decreased by DHA injection. Moreover, Western blotting showed that Bax, cleaved caspase-3 and CHOP were notably increased in the NaIO3 group but were significantly decreased by DHA injection. Collectively, intravitreal injection of DHA is safe and effective in select doses in a NaIO3-induced AMD rat model. The current results suggest that intravitreal injection of DHA may be a new avenue for the treatment of AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study

    PubMed Central

    Satarian, Leila; Nourinia, Ramin; Safi, Sare; Kanavi, Mozhgan Rezaei; Jarughi, Neda; Daftarian, Narsis; Arab, Leila; Aghdami, Nasser; Ahmadieh, Hamid; Baharvand, Hossein

    2017-01-01

    Purpose: To examine the safety of a single intravitreal injection of autologous bone Marrow Mesenchymal stem cells (MSCs) in patients with advanced retinitis pigmentosa (RP). Methods: A prospective, phase I, nonrandomized, open-label study was conducted on 3 eyes of 3 volunteers with advanced RP. Visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, fundus auto-fluorescence, fluorescein angiography and multifocal electroretinography were performed before and after an intravitreal injection of approximately one-million MSCs. The patients were followed for one year. Further evaluation of MSCs was performed by injection of these cells into the mouse vitreous cavity. Results: No, adverse events were observed in eyes of 2 out of 3 patients after transplantation of MSCs. These patients reported improvements in perception of the light after two weeks, which lasted for 3 months. However, severe fibrous tissue proliferation was observed in the vitreous cavity and retrolental space of the third patient's eye, which led to tractional retinal detachment (TRD), iris neovascularization and formation of mature cataract. Injection of this patient's MSCs into the vitreous cavity of mice also resulted in fibrosis; however, intravitreal injections of the two other patients' cells into the mouse vitreous did not generate any fibrous tissue. Conclusion: Intravitreal injection of autologous bone marrow MSCs into patients' eyes with advanced RP does not meet safety standards. Major side effects of this therapy can include fibrosis and TRD. We propose thorough evaluation of MSCs prior to transplantation by intravitreal injection in the laboratory animals.\\ PMID:28299008

  1. Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study.

    PubMed

    Satarian, Leila; Nourinia, Ramin; Safi, Sare; Kanavi, Mozhgan Rezaei; Jarughi, Neda; Daftarian, Narsis; Arab, Leila; Aghdami, Nasser; Ahmadieh, Hamid; Baharvand, Hossein

    2017-01-01

    To examine the safety of a single intravitreal injection of autologous bone Marrow Mesenchymal stem cells (MSCs) in patients with advanced retinitis pigmentosa (RP). A prospective, phase I, nonrandomized, open-label study was conducted on 3 eyes of 3 volunteers with advanced RP. Visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, fundus auto-fluorescence, fluorescein angiography and multifocal electroretinography were performed before and after an intravitreal injection of approximately one-million MSCs. The patients were followed for one year. Further evaluation of MSCs was performed by injection of these cells into the mouse vitreous cavity. No, adverse events were observed in eyes of 2 out of 3 patients after transplantation of MSCs. These patients reported improvements in perception of the light after two weeks, which lasted for 3 months. However, severe fibrous tissue proliferation was observed in the vitreous cavity and retrolental space of the third patient's eye, which led to tractional retinal detachment (TRD), iris neovascularization and formation of mature cataract. Injection of this patient's MSCs into the vitreous cavity of mice also resulted in fibrosis; however, intravitreal injections of the two other patients' cells into the mouse vitreous did not generate any fibrous tissue. Intravitreal injection of autologous bone marrow MSCs into patients' eyes with advanced RP does not meet safety standards. Major side effects of this therapy can include fibrosis and TRD. We propose thorough evaluation of MSCs prior to transplantation by intravitreal injection in the laboratory animals.\\.

  2. Changes of choroidal neovascularization in indocyanine green angiography after intravitreal ranibizumab injection.

    PubMed

    Lee, Ji Eun; Kim, Hyun Woong; Lee, Sang Joon; Lee, Joo Eun

    2015-05-01

    To investigate vascular structural changes of choroidal neovascularization (CNV) followed by intravitreal ranibizumab injections using indocyanine green angiography. A total of 31 patients with exudative age-related macular degeneration and CNV whose structures were identifiable in indocyanine green angiography were included. Ranibizumab was injected into the vitreous cavity once a month for 3 months and then as needed for the next 3 months prospectively. Indocyanine green angiography was performed at baseline, 3, and 6 months. Early to midphase images of the indocyanine green angiography in the details of vascular structure of the CNV were discerned the best were used in the image analysis. Vascular structures of CNV were described as arteriovenular and capillary components, and structural changes were assessed. Arteriovenular components were observed in 29 eyes (94%). Regression of the capillary components was observed in most cases. Although regression of arteriovenular component was noted in 14 eyes (48%), complete resolution was not observed. The eyes were categorized into 3 groups according to CNV structural changes: the regressed (Group R, 10 eyes, 31%), the matured (Group M, 7 eyes, 23%), and the growing (Group G, 14 eyes, 45%). In Group R, there was no regrowth of CNV found at 6 months. In Group M, distinct vascular structures were observed at 3 months and persisted without apparent changes at 6 months. In Group G, growth or reperfusion of capillary components from the persisting arteriovenular components was noted at 6 months. Both capillary and arteriovenular components were regressed during monthly ranibizumab injections. However, CNV regrowth was observed in a group of patients during the as-needed treatment phase.

  3. Ocular Decompression with Cotton Swabs Lowers Intraocular Pressure Elevation Following Intravitreal Injection

    PubMed Central

    Gregori, Ninel Z.; Weiss, Matthew J.; Goldhardt, Raquel; Schiffman, Joyce C.; Vega, Edgardo; Mattis, Cherrie-Ann; Shi, Wei; Kelley, Linda; Hernandez, Vilma; Feuer, William J.

    2013-01-01

    Objective To determine the effect of pre-injection ocular decompression by cotton swabs on the immediate rise in intraocular pressure (IOP) after intravitreal injections. Methods Forty-eight patients receiving 0.05-ml ranibizumab injections in a retina clinic were randomized to two anesthetic methods in each eye on the same day (if bilateral disease) or on consecutive visits (if unilateral disease). One method utilized cotton swabs soaked in 4% lidocaine applied to the globe with moderate pressure and the other 3.5% lidocaine gel applied without pressure. IOPs were recorded at baseline (before injection) and at 0, 5, 10, and 15 minutes after the injection until the IOP was ≤30 mmHg. The IOP elevations from baseline were compared after the two anesthetic methods. Results The pre-injection mean IOP (SD, mmHg) was 15.5 (3.3) before the cotton swabs and 15.9 (3.0) before the gel (p=0.28). Mean IOP (SD, mmHg) change immediately after injection was 25.7 (9.2) after the cotton swabs and 30.9 (9.9) after the gel (P=0.001). Thirty-five percent of gel eyes had IOP ≥50 mmHg compared to only 10% of cotton swab eyes immediately after the injection (P<0.001). Conclusion Decompressing the eye with cotton swabs during anesthetic preparation prior to an intravitreal injection produces a significantly lower IOP spike after the injection. PMID:23632408

  4. A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Steven L.

    2015-01-01

    Purpose Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). Methods We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. Results A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. Conclusions A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION. PMID:26624498

  5. Intravitreal Injection of Splice-switching Oligonucleotides to Manipulate Splicing in Retinal Cells.

    PubMed

    Gérard, Xavier; Perrault, Isabelle; Munnich, Arnold; Kaplan, Josseline; Rozet, Jean-Michel

    2015-09-01

    Leber congenital amaurosis is a severe hereditary retinal dystrophy responsible for neonatal blindness. The most common disease-causing mutation (c.2991+1655A>G; 10-15%) creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. Recently, we reported that splice-switching oligonucleotides (SSO) allow skipping of the mutant cryptic exon and the restoration of ciliation in fibroblasts of affected patients, supporting the feasibility of a SSO-mediated exon skipping strategy to correct the aberrant splicing. Here, we present data in the wild-type mouse, which demonstrate that intravitreal administration of 2'-OMePS-SSO allows selective alteration of Cep290 splicing in retinal cells, including photoreceptors as shown by successful alteration of Abca4 splicing using the same approach. We show that both SSOs and Cep290 skipped mRNA were detectable for at least 1 month and that intravitreal administration of oligonucleotides did not provoke any serious adverse event. These data suggest that intravitreal injections of SSO should be considered to bypass protein truncation resulting from the c.2991+1655A>G mutation as well as other truncating mutations in genes which like CEP290 or ABCA4 have a mRNA size that exceed cargo capacities of US Food and Drug Administration (FDA)-approved adeno-associated virus (AAV)-vectors, thus hampering gene augmentation therapy.

  6. Incidence of acute endophthalmitis after intravitreal bevacizumab injection in a single clinical center.

    PubMed

    Falavarjani, Khalil Ghasemi; Modarres, Mehdi; Hashemi, Masih; Parvaresh, Mohammad M; Naseripour, Masood; Zare-Moghaddam, Abbas; Nekoozadeh, Shahbaz

    2013-05-01

    To assess the rate of infectious endophthalmitis in a single clinical center in Iran and to compare the rate of endophthalmitis in patients receiving postinjection antibiotics with those who did not. A retrospective chart review of patients who received intravitreal injections of bevacizumab was undertaken. Cases of clinical diagnoses of endophthalmitis were reviewed. Bevacizumab was obtained at the time of injection from a commercially available vial after aseptic cleansing of the rubber cover. Five patients (six eyes) developed clinical endophthalmitis after the intravitreal bevacizumab injection. The risk per injection was 0.10% (6/5,901). One culture-positive case was found overall. Postinjection antibiotic drops were prescribed for 68% of eyes. All endophthalmitis cases were among those who received postoperative antibiotic eye drops. The difference in the rates of endophthalmitis between those receiving postinjection antibiotics and those who did not was not statistically significant (P = 0.18). A low risk of endophthalmitis consistent with the range of previous studies was observed notwithstanding the usage of multiple use of a single vial. Postinjection antibiotic drops may not be necessary.

  7. Progression to macula-off tractional retinal detachment after a contralateral intraoperative intravitreal bevacizumab injection for proliferative diabetic retinopathy.

    PubMed

    Zlotcavitch, Leonid; Flynn, Harry W; Avery, Robert L; Rachitskaya, Aleksandra

    2015-01-01

    We report a patient with progression to a macula-off tractional retinal detachment in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection. A 32-year-old diabetic man noted decreased vision in his left eye 1 week following 25 gauge pars plana vitrectomy, gas tamponade, and intraoperative injection of bevacizumab in his right eye. Left eye visual acuity decreased from 20/80 to 20/200, and macula-off tractional retinal detachment was seen on clinical exam and imaging. Progression of tractional retinal detachment associated with proliferative diabetic retinopathy in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection may occur.

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

    PubMed Central

    Lu, Yan; Zhou, Nan; Huang, Xiao; Cheng, Jin-Wei; Li, Feng-Qian; Wei, Rui-Li; Cai, Ji-Ping

    2014-01-01

    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 24 animals 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 analyse 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, and also 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

  9. Incidence of Presumed Silicone Oil Droplets in the Vitreous Cavity After Intravitreal Bevacizumab Injection With Insulin Syringes.

    PubMed

    Khurana, Rahul N; Chang, Louis K; Porco, Travis C

    2017-07-01

    Intravitreal bevacizumab is a frequently used antivascular endothelial growth factor medication in the United States, but its off-label use is associated with risks associated with the compounding preparation. To determine the incidence of presumed silicone oil droplets after intravitreal bevacizumab was prepared in insulin syringes by a compounding pharmacy. A retrospective review was conducted of 60 patients who experienced intravitreal silicone oil droplets in the eye after intravitreal bevacizumab injections from a single specialist practice from October 1, 2015, to November 30, 2016. Bevacizumab, 1.25 mg/0.05 mL, was delivered in insulin syringes with a 31-gauge needle. Small, round clear spheres in vitreous on dilated biomicroscopic retinal examination. Over a 14-month period involving 6632 intravitreal bevacizumab injections, 60 cases (35 [58%] women) of intravitreal silicone droplets were identified. Mean [SD] age of the patients was 80 [12] years; the population comprised 48 white, 9 Asian, and 3 Hispanic patients. The incidence of silicone oil droplet injections was 0.03% (1 of 3230) from October 2015 to April 2016 and 1.7% (59 of 3402) from May to November 2016 (Fisher exact test, P < .001; odds ratio [OR], 57; 95% CI, 9.8-2260). From May to November 2016, nonpriming the syringe before the intravitreal injection had a higher risk of intravitreal silicone oil droplets compared with priming the syringe (6.4% [47 of 739] vs 0.5% [12 of 2627]; Fisher exact test, P < .001; OR, 15.1; 95% CI, 7.9-33.4). Among the 60 cases, 41 patients (68%) were symptomatic, and the main symptom was floaters with spots of light. Among the patients with floaters, 36 (88%) improved over time (range, 2-8 months) despite the silicone droplets still being present on ophthalmoscopic examination. An increase in intravitreal silicone oil associated with bevacizumab prepared with insulin syringes was documented. Priming the syringe before injection was associated with a lower

  10. Evaluation of triamcinolone acetonide following intravitreal injection in New Zealand white rabbits.

    PubMed

    McGee, David H; Dembinska, Olga; Gruebbel, Margarita M

    2005-01-01

    The safety of intravitreally injected triamcinolone acetonide suspension (TA) was evaluated in rabbits. Each animal received 0.1 ml (1) balanced salt solution (BSS) vehicle, (2) formulation vehicle, (3) 4% TA (4-mg dose), (4) 16% TrAc (16-mg dose) or (5) 25% TA (25-mg dose) as a single intravitreal injection into the right eye. The left eyes served as untreated controls. All animals were observed for 1 month following treatment. In-life evaluations included clinical signs, body weights, slit-lamp biomicroscopic and indirect ophthalmoscopic examinations, intraocular pressure and corneal thickness measurements, and electroretinograms (ERGs). Ocular tissues were harvested following a 1-month post-treatment observation period, fixed, processed, and evaluated by light microscopy. No significant or treatment-related clinical signs were observed for any animals during the study. The opaque white test article was clearly visible in the eye for all TrAc-treated groups, and remained so throughout the study. No statistically significant differences in mean body weights were present between the control and treatment groups, though changes in body weight varied. Corneal thickness was slightly reduced for some treated groups. Intraocular pressures were not statistically significantly different from controls for any treatment group. No significant changes in ERG were evident between treatment groups or from baseline readings. Microscopically, basophilic material (presumed to be drug) was seen in the vitreous of all or most treated eyes, with accumulations in the vitreous or in clumps adjacent to the retinal surface. No pathological changes were observed in the retina or other ocular structures. Triamcinolone acetonide suspension was safe and well tolerated following intravitreal injection in New Zealand white rabbits.

  11. Safety of bilateral same-day intravitreal injections of anti-vascular endothelial growth factor agents

    PubMed Central

    Ruão, Miguel; Andreu-Fenoll, María; Dolz-Marco, Rosa; Gallego-Pinazo, Roberto

    2017-01-01

    Purpose The aim was to evaluate the safety of bilateral same-day injections with intravitreal antiangiogenic drugs for macular diseases. Methods Cross-sectional retrospective review of unilateral and bilateral same-day antiangiogenic injections was conducted between January 2011 and March 2016 in the Unit of Macula, University and Polytechnic Hospital La Fe (Valencia, Spain). A total of 8,172 injections were administered, among which 6,560 were unilateral and 1,612 were bilateral injections. Patients were included in the study regardless of the diagnosis. Ranibizumab and aflibercept were the antiangiogenic drugs used. The presence of endophthalmitis or retinal detachment was evaluated. Results A total of 1 (0.012%) culture-proven endophthalmitis and 19 (0.233%) acute intraocular inflammations were registered. In the unilateral injections group, there were 18 (0.274%) acute intraocular inflammations and 1 (0.015%) culture-proven endophthalmitis. One (0.062%) of the 1,612 bilateral same-day injections had a unilateral acute intraocular inflammation, and there were no culture-proven endophthalmitis in this group. Conclusion Bilateral same-day injections are more convenient for patients and their caregivers than the unilateral injections administered on different days. In our study, the prevalence of culture-proven endophthalmitis and acute intraocular inflammation was lower in the bilateral injections than in the unilateral group. These data support the idea that bilateral same-day injections are a safe and valid treatment to use in our clinical practice. PMID:28203056

  12. Peristence of triamcinolone crystals after intra-vitreal injection: Benign crystalline hyaloidopathy

    PubMed Central

    Zarifa, Rafik; Shaikh, Saad; Kester, Elizabeth

    2013-01-01

    We report a case of unusually long persistence of triamcinolone crystals after intra-vitreal injection. Crystals were noted on fundus examination predominantly confined to the posterior pole. Optical coherence tomography localized the crystals to the posterior hyaloidal surface. Over 6 years of follow-up the patient has retained good visual acuity and no observable changes in the retina. As the condition clinically resembles both crystalline maculopathy and asteroid hyalosis, we suggest the term ‘drug-induced benign crystalline hyaloidopathy’. PMID:23685493

  13. Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections

    PubMed Central

    Levin, Ariana M; Rusu, Irene; Orlin, Anton; Gupta, Mrinali P; Coombs, Peter; D’Amico, Donald J; Kiss, Szilárd

    2017-01-01

    Purpose The aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy. Methods This study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders. Results Twelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation. Conclusion In patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA. PMID:28176934

  14. Apoptosis and electroretinogram after intravitreal injection of methotrexate in an experimental rabbit model.

    PubMed

    Aly, Eman; Ebrahim, Amal

    2016-04-01

    The aim of this study was to explore the changes in electroretinogram of rabbit retina and apoptosis in methotrexate-induced toxicity. Rabbits were divided into 5 groups. Group I served as control in which saline solutions was injected intravitreally. Methotrexate (800 μg, 1.76 μmol) was injected into the vitreous of both eyes of rabbits groups II, III, IV and V by an insulin injector with a 26 gauge needle under general anesthesia. Retinal function was assessed by electroretinogram (ERG) after 2, 4, 10 days and one month then animals were decapitated. The eyes were enucleated and processed for DNA fragmentation studies by gel electrophoresis to retinae and measurement of caspase-3 activities. The results indicated a significant reduction (p ˂ 0.05) in a- and b-wave, a time-dependent appearance of the typical ladder pattern of internucleosomal fragmentation, a characteristic of apoptosis and increase of relative caspase-3 activity after methotrexate intravitreal injection. Methotrexate lead to apoptosis, increase of caspase-3 and affect retinal function.

  15. Thermo-responsive hydrogels for intravitreal injection and biomolecule release

    NASA Astrophysics Data System (ADS)

    Drapala, Pawel

    In this dissertation, we develop an injectable polymer system to enable localized and prolonged release of therapeutic biomolecules for improved treatment of Age-Related Macular Degeneration (AMD). Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and cross-linked with poly(ethylene glycol) (PEG) poly(L-Lactic acid) (PLLA) copolymer were synthesized via free-radical polymerization. These materials were investigated for (a) phase change behavior, (b) in-vitro degradation, (c) capacity for controlled drug delivery, and (d) biocompatibility. The volume-phase transition temperature (VPTT) of the PNIPAAm- co-PEG-b-PLLA hydrogels was adjusted using hydrophilic and hydrophobic moieties so that it is ca. 33°C. These hydrogels did not initially show evidence of degradation at 37°C due to physical cross-links of collapsed PNIPAAm. Only after addition of glutathione chain transfer agents (CTA)s to the precursor did the collapsed hydrogels become fully soluble at 37°C. CTAs significantly affected the release kinetics of biomolecules; addition of 1.0 mg/mL glutathione to 3 mM cross-linker accelerated hydrogel degradation, resulting in 100% release in less than 2 days. This work also explored the effect of PEGylation in order to tether biomolecules to the polymer matrix. It was demonstrated that non-site-specific PEGylation can postpone the burst release of solutes (up to 10 days in hydrogels with 0.5 mg/mL glutathione). Cell viability assays showed that at least two 20-minute buffer extraction steps were needed to remove cytotoxic elements from the hydrogels. Clinically-used therapeutic biomolecules LucentisRTM and AvastinRTM were demonstrated to be both stable and bioactive after release form PNIPAAm-co-PEG-b-PLLA hydrogels. The thermo-responsive hydrogels presented here offer a promising platform for the localized delivery of proteins such as recombinant antibodies.

  16. Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD

    PubMed Central

    Kuriyan, Ajay E.; Albini, Thomas A.; Townsend, Justin H.; Rodriguez, Marianeli; Pandya, Hemang K.; Leonard, Robert E.; Parrott, M. Brandon; Rosenfeld, Philip J.; Flynn, Harry W.; Goldberg, Jeffrey L.

    2017-01-01

    Summary Adipose tissue–derived “stem cells” have been increasingly used by “stem-cell clinics” in the United States and elsewhere to treat a variety of disorders. We evaluated three patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue–derived “stem cells” at one such clinic in the United States. In these three patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients’ severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients’ visual acuity ranged from 20/200 to no light perception. PMID:28296617

  17. POOLED ESTIMATES OF INCIDENCE OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS WITH AND WITHOUT TOPICAL ANTIBIOTIC PROPHYLAXIS.

    PubMed

    Reibaldi, Michele; Pulvirenti, Alfredo; Avitabile, Teresio; Bonfiglio, Vincenza; Russo, Andrea; Mariotti, Cesare; Bucolo, Claudio; Mastropasqua, Rodolfo; Parisi, Guglielmo; Longo, Antonio

    2017-03-06

    To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity. From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group. Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

  18. Experiences of patients undergoing repeated intravitreal anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration.

    PubMed

    Boyle, Jessica; Vukicevic, Meri; Koklanis, Konstandina; Itsiopoulos, Catherine; Rees, Gwyneth

    2017-01-09

    Current therapy to slow disease progression in patients with neovascular age-related macular degeneration (AMD) entails regular intravitreal anti-vascular endothelial growth factor (VEGF) injections, often indefinitely. Little is known about the burden imposed on patients by this repetitive treatment schedule and how this can be best managed. The aim of this study was to explore the psychosocial impact of repeated intravitreal injections on patients with neovascular AMD. Forty patients (16 males, 24 females) with neovascular AMD undergoing anti-VEGF treatment were recruited using purposive sampling from a private ophthalmology practice and public hospital in Melbourne. Patients were surveyed using the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ; Bradley, Health Psychology Research Unit, Surrey, England) and underwent semi-structured, one-on-one interviews. Interview topics were: treatment burden and satisfaction; tolerability; barriers to adherence; treatment motivation; and patient education. Interviews were audio recorded and thematic analysis performed using NVivo 10 (QSR International, Doncaster, Australia). Patients recognised the importance of treatment to preserve eyesight, yet experienced significant psychosocial and practical burden from the treatment schedule. Important issues included treatment-related anxiety, financial considerations and transport burden placed on relatives or carers. Many patients were restricted to sedentary activities post-injection owing to treatment side effects. Patients prioritised treatment, often sacrificing family, travel and social commitments owing to a fear of losing eyesight if treatment was not received. Whilst anti-VEGF injections represent the current mainstay of treatment for neovascular AMD, the ongoing treatment protocol imposes significant burden on patients. An understanding of the factors that contribute to the burden of treatment may help inform strategies to lessen its impact and assist

  19. Incidence of endophthalmitis following intravitreal Bevacizumab injection at a tertiary care hospital in Eastern Province of Saudi Arabia

    PubMed Central

    Cheema, Rizwan A.; Alshihry, Ahmad M.; Cheema, Haider R.

    2014-01-01

    The aim of this communication is to report the incidence of endophthalmitis following the use of intravitreal Bevacizumab (IVB) at a tertiary care hospital in the Eastern province of Saudi Arabia. A total of 2769 intravitreal Bevacizumab injections were carried out between January 2009 and April 2014. During this period, one case of endophthalmitis following IVB injection occurred. The overall incidence of clinical endophthalmitis was 0.036% (1/2769; 95% confidence interval: 0.0001–0.002%). This compares favorably with studies reported from other parts of the world. PMID:25892933

  20. [Intravitreal injections of medications in Germany. Contract situation and legal conditions].

    PubMed

    Ziemssen, F; Wiedemann, P; Kampik, A; Holz, F; Bartz-Schmidt, K U

    2009-05-01

    Despite the increasing application of both approved and off-label drugs for intravitreal administration, the German health system still does not provide an accounting code for the procedure of intravitreal injections. Health insurances and politicians are exerting pressure in order to limit the expected increase in the number of medications and costs due to demographic factors. Although the price for the drug can be determined by the manufacturer, a standing committee has to agree on the fee to be charged for the medical service of injection and subsequent examinations. Until the missing arrangement has been made, each individual surgeon can balance accounts with the patients who have claim for reimbursement. Many contracts have recently been made in order to regulate the extent of performance and charges for the application of medications and follow-up examinations to reduce administration costs. Due to medical liability and ethical code, physicians are obliged to provide a cost-effective and adequate treatment as well as a comprehensive preoperative patient education including efficacy, potential complications, limited prescription and free choice of a medical practitioner. It also appears prudent to explain relevant terms such as 'off-label' and 'level of evidence'. To prevent any suspicion of personal advantage, patients should be informed if placed contracts do not allow equal reimbursement for the same treatment or similar drugs.

  1. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

    PubMed Central

    Mansour, Ahmad M.; Al Kahtani, Eman; Zegarra, Hernando; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A.; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J.; Pulido, Jose S.; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S.; Gentile, Ronald C.; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y. Y.; Massoud, Vicky; Ghazi, Nicola G.

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma. PMID:25147732

  2. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma.

    PubMed

    Mansour, Ahmad M; Arevalo, J Fernando; Al Kahtani, Eman; Zegarra, Hernando; Abboud, Emad; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J; Pulido, Jose S; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S; Gentile, Ronald C; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y Y; Massoud, Vicky; Ghazi, Nicola G

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.

  3. Intravitreal bevacizumab injections for diabetic macular edema – predictors of response: a retrospective study

    PubMed Central

    Joshi, Lavnish; Bar, Asaf; Tomkins-Netzer, Oren; Yaganti, Satish; Morarji, Jiten; Vouzounis, Panayiotis; Seguin-Greenstein, Sophie; Taylor, Simon R; Lightman, Sue

    2016-01-01

    Background Outcomes of intravitreal antivascular endothelial growth factor injections are variable among patients with diabetic macular edema (DME). The aim of this study was to determine the ocular and systemic predictors of DME response to intravitreal bevacizumab (IVB). Methods Retrospective review over 2 years of 78 eyes from 54 patients. An anatomical response to IVB was defined as a 20% reduction in central macula thickness after the first course (three injections) of IVB. Results Twenty-eight percent of patients had an anatomical response after the first course of IVB. Systemic hypertension (odds ratio, 95% confidence interval: 12.1, 0.7–21) was a statistically significant predictor (P=0.025) of a good response to IVB, whereas previous macular laser was a statistically significant (P=0.0005) predictor of a poor response (0.07, 0.01–0.32). Sixty-eight percent of eyes underwent subsequent treatment for DME after the first course of IVB. The visual acuity gain at 24 months in hypertensive (0.7±3.6 letters) and nonhypertensive (5.2±3.7 letters) patients was not significantly different (P=0.41). Conclusion Hypertension and previous macular laser were positive and negative predictors of response to IVB, respectively. However, long-term visual acuity changes were not significantly different between eyes with and without systemic hypertension. PMID:27799737

  4. Viral Retinitis Following Intravitreal Triamcinolone Injection in Patients with Predisposing Medical Comorbidities

    PubMed Central

    Shah, Ankur M.; Oster, Stephen F.; Freeman, William R.

    2009-01-01

    Purpose To review the cases of viral retinitis following intravitreal steroid administration at a single center, to estimate the incidence, and to propose risk factors for its occurrence. Design Retrospective, observational case series Methods 736 intravitreal triamcinolone (IVTA) injections were given in the clinic and operating room by three retina specialists at a single academic medical center, between September 2002 to November 2008. Inclusion criteria were simply a history of one or more IVTA injections during the period. The overall incidence of viral retinitis following IVTA was calculated. Subsequently, a chart audit was performed to estimate the number of patients with immune-altering conditions who had received IVTA during the time period, and the incidence within this subgroup was calculated. Results Viral retinitis developed following IVTA injection in three patients, yielding an overall incidence of 3/736 or 0.41%. An estimated 334 injections were given to patients with an immune-altering condition, including diabetes. All three of the patients who developed viral retinitis following IVTA possessed abnormal immune systems, yielding an incidence rate of 3/334 or 0.90% within this subgroup. Conclusions Our high reported incidence for this potentially devastating complication can be attributed to multiple factors, including coexisting medical immunocompromising comorbidities, a higher dose with a longer duration of local immunosuppression in the vitreous, multiple injections, as well as previous viral retinitis. Caution with a high index of clinical suspicion and frequent follow-up is advised in patients receiving IVTA with potentially immune-altering conditions, even after apparent immune recovery. PMID:20172069

  5. Lowered intraocular pressure in a glaucoma patient after intravitreal injection of ocriplasmin

    PubMed Central

    McClintock, Michael; MacCumber, Mathew W

    2015-01-01

    We report the case of a glaucoma patient who received a single intravitreal injection of 125 µg ocriplasmin for vitreomacular traction in the right eye. The patient had bilateral advanced glaucoma and had previously undergone an implantation of an Ahmed glaucoma valve in the right eye and trabeculectomy in both eyes. The patient was using three topical ophthalmic intraocular pressure (IOP)-lowering medications on the day of injection. Baseline uncorrected Snellen visual acuity was 20/80-1 and IOP was 19 mmHg. Resolution of vitreomacular traction was achieved 1 week after injection. IOP was transiently decreased, reaching a maximum reduction of 12 mmHg below baseline at 1 month after injection, when serous choroidal effusion was also present. IOP returned to baseline levels and choroidal effusion resolved at 2 months after injection of IOP-lowering medication. Vitrectomy with epiretinal membrane and internal limiting membrane peeling, endolaser photocoagulation, and fluid–gas exchange were performed in the right eye ~3.5 months after injection to treat persistent epiretinal membrane, and presumed tractional retinal detachment. Final visual acuity was 20/50+ and IOP was 18 mmHg at 16 weeks after surgery. To our knowledge, this is the first report of IOP reduction and serous choroidal effusion after ocriplasmin injection. PMID:26604668

  6. Practice patterns of ophthalmologists administering intravitreal injections in Europe: a longitudinal survey

    PubMed Central

    Huang, Kui; Sultan, Marla B; Zhou, Duo; Tressler, Charles S; Mo, Jingping

    2016-01-01

    Purpose This study was performed to understand the practice patterns of ophthalmologists administering intravitreal (IVT) injections in Europe after the procedure became routine. Methods As part of a prospective, multinational, non-interventional cohort study in 13 countries in Europe between 2006 and 2012, ophthalmologists completed the Baseline Questionnaire and the Follow-up Questionnaire 1 year after baseline. Results and discussion Of the 125 ophthalmologists who participated in the study, 113 (90.4%) completed the Baseline Questionnaire. Most of these ophthalmologists were medical retina specialists (43.0%). The median number of IVT injections that the ophthalmologists performed per month during the year prior to completing the Baseline Questionnaire was 20.0. The majority of the ophthalmologists had performed their last IVT injection prior to completing the questionnaire in an operating room or theater (68.4%). When performing IVT injections, a majority of the ophthalmologists reported applying povidone–iodine (90.4%) before IVT injections and topical antibiotics right after IVT injections (89.5%). In addition, 81.6% of the ophthalmologists reported using a sterile adhesive eye drape and 80.7% reported using an eyelid speculum. In all, 95 ophthalmologists (76%) completed the Follow-up Questionnaire. The median number of IVT injections performed per month during the year prior to completing the Follow-up Questionnaire by these ophthalmologists was increased to 35. The results of the Follow-up Questionnaire on administering IVT injections were similar to those of the Baseline Questionnaire. A majority of the ophthalmologists reported applying povidone–iodine (87.4%) before IVT injections, topical antibiotics right after IVT injections (89.5%), and an eyelid speculum (85.3%). Conclusion The results of this study indicated a good adherence to all aspects of the guidelines on IVT injections. It seemed that ophthalmologists were more experienced in IVT

  7. [Azithromycin in prophylaxis of intravitreal injections in patients with wet age-related macular degeneration].

    PubMed

    Figurska, Małgorzata

    2011-01-01

    Endophthalmitis is one of the most dangerous complications after intravitreous drug injection. Preparing a patient to the injection general and topical endophtalmitis development risk factors should be eliminated. Antibiotic injection prophylaxis is still an important issue. This research has to evaluate effectiveness and tolerance of Azithromycin (Azyter, Thea), in injection as an antibiotic prophylaxis in patients suffering from age-related macular degeneration (AMD). The study was conducted in Ophtalmology Department (Medical Military Institute, Warsaw, Poland), in the group of 52 patients, who underwent 52 intraocular injections of anti-VEGF because of AMD. Topical Azithromycin had been administrated twice a day to both eyes in 2 days before injection. On the third day injection was performed in aseptic conditions. One drop of Azithromycin had been administrated to each eye directly before injection and one drop after the procedure. At that moment antibiotic prophylaxis was terminated. Topical tolerance and effectiveness were evaluated. In 2 cases (3.8%) intensive allergic reaction was reported (significant conjuctives oedema, itch, bloodshot), what caused change of antibiotic. In 5 cases (9%) light bloodshot was reported. 12 patients (23%) reported light or moderate foreign body sensation and in 2 cases (3.8%) the sensation was significant. No reaction of ophthalmic inflammation was reported 5 days after injection, moreover foreign body sensation and bloodshot were absent. 30 patients (57%) were satisfied with new and simplier scheme of antibiotic injection prophylaxis (twice a day for 3 days). Azithromycin is a comfortable alternative for other topical antibiotics, especially in repetitive procedures like anti-VEGF injections. High Azithromycin concentration in tissues, tear film, and on the ophthalmic surface, protects injection site and inhibits growth of primary and mutual bacterial colonies. Short-term exposition to Azithromycin decrases risk of drug

  8. [Managment of subretinal heamorrhages within the macular area using intravitreal injections of recombined tissue plasminogen activator, sulphur hexafluoride and ranihizumab--preliminary report].

    PubMed

    Miniewicz, Joanna; Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Boźena

    2015-01-01

    Submacular hemorrhages cause serious vision impairment. Patient observation, waiting for the spontaneous blood reabsorption and resolution of the haemorrhage leads to the severe damage to retinal tissue as a result of scar formation. The paper presents 7 cases of patients with submacular haemorrhages treated with intravitreal injections of recombined tissue plasminogen activator (rtPA) and sulphur hexafluoride (SFG). In 4 cases, the haemorrhage was secondary to AMD, in two cases to trauma, and it was idiopathic in one case. All patients were treated with intravitreal injections of rtPA and SF6 for thrombolysis and pneumatic displacement of haemorrhage outside macular structures. Ranibizumab was additionally administered to patients with age-related macular degeneration. Such treatment improved visual acuity in all patients, reducing the central retinal thickness as shown in follow-up optical coherence tomography. The presented treatment of submacular hemorrhages with intravitreal injections of rtPA and SF6 provided good results, but in order to develop a standard management algorithm for this disease, the analysis of larger patient sample is required.

  9. Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection.

    PubMed

    Li, Huiling; Palamoor, Mallika; Jablonski, Monica M

    2016-10-01

    Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5 mg/ml and 10 mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.

  10. Dual Intravitreal Injections With Foscarnet and Ganciclovir for Ganciclovir-Resistant Recurrent Cytomegalovirus Retinitis in a Congenitally Infected Infant.

    PubMed

    Boss, Joseph D; Rosenberg, Kevin; Shah, Rajiv

    2016-10-22

    Resistant strains of cytomegalovirus can be difficult to treat in cases of congenital cytomegalovirus retinitis. The authors describe a case of recurrent bilateral congenital cytomegalovirus retinitis in an immunocompetent newborn with ganciclovir resistance successfully treated uniquely with dual therapy of intravenous ganciclovir and foscarnet and dual intravitreal injections with ganciclovir and foscarnet. [J Pediatr Ophthalmol Strabismus. 2016;53:e58-e60.].

  11. Acute angle closure attack after an intravitreal bevacizumab injection for branch retinal vein occlusion: a case report.

    PubMed

    Jeong, Seongyong; Sagong, Min; Chang, Woohyok

    2017-03-14

    Intravitreal injection is widely used to treat retinal vein occlusion, and acute angle closure (AAC) is an exceptional complication of intravitreal injection. The authors report a case of AAC that occurred immediately after administering intravitreal bevacizumab to treat branch retinal vein occlusion (BRVO). A 65-year-old woman was referred to the retina clinic of a tertiary referral center for the treatment of macular edema secondary to BRVO. On slit lamp examination, anterior chamber (AC) depth was shallow (3 corneal thicknesses centrally, 1/4 corneal thicknesses peripherally) in both eyes. Intraocular pressure (IOP) was 19 mmHg in both eyes, and refractive error was +1.00 diopter sphere in both eyes. A gonioscopy exam demonstrated narrow angle of over 180° in both eyes. To treat the macular edema, bevacizumab was injected into her right eye intravitreally. After two bevacizumab injections, the macular edema regressed but recurred 5 months later, and thus, a third injection was performed. The next day, she visited our emergency department complaining of persistent ocular pain in her right eye. The right pupil had dilated to 6 mm diameter and was fixed. Slit lamp exam revealed diffuse corneal edema in her right eye, which had an IOP of 56 mmHg. After administration of intravenous mannitol, the IOP fell to 14 mmHg and the corneal edema disappeared. Subsequently, a glaucoma specialist performed laser iridotomy on the right eye. Although AAC is a rare complication of intravitreal injection, it can occur in a patient with risk factors such as hyperopic eye or narrow angle.

  12. Effects of an intravitreal injection of interleukin-35-expressing plasmid on pro-inflammatory and anti-inflammatory cytokines.

    PubMed

    Hou, Chao; Wu, Qianni; Ouyang, Chen; Huang, Ting

    2016-09-01

    In order to explore the potential effects of interleukin (IL)-35 on IL-10, transforming growth factor-β (TGF-β), interferon-γ (INF)-γ, IL-12 and IL-17, a pcDNA3.1‑IL-35 plasmid was injected into the vitreous cavity of BALB/c mice. Enzyme-linked immunosorbent assay, western blot analysis and quantitative PCR analysis were performed to confirm the successful expression of IL-35. Slit-lamp biomicroscopy, hematoxylin and eosin staining and immunofluorescence were employed to detect the status of eyes, and western blot analysis was performed to examine the expression of corneal graft rejection-related cytokines. There were no abnormalities in the eyes pre-mydriasis or post-mydriasis and no injuries to the cornea or retina following the injection of IL-35-expressing plasmid. An immunofluorescence assay detected the positive expression of IL-35 in corneal epithelial cells from IL-35‑injected mice and negative staining in the control group. Further study revealed that IL-35 enhanced the expression of IL-10 and TGF-β which reached their highest levels at 1 and 2 weeks after injection, respectively (p<0.01). Moreover, the expression of INF-γ and IL-12 was decreased significantly at 2 weeks after the injection of IL-35-expressing plasmid (p<0.05), and the expression of IL-17 was suppressed notably at 4 weeks after the injection (p<0.05). The intravitreal injection of IL-35-expressing plasmid in mice downregulates the expression of pro-inflammatory cytokines and upregulates the expression of anti-inflammatory cytokines. Thus, IL-35 may further be assessed as a potential target for the treatment of corneal graft rejection.

  13. Hypothalamic-pituitary-adrenal axis function following intravitreal triamcinolone acetonide injection.

    PubMed

    Amiran, Maoz D; Yeung, Sonia N; Lang, Yaron; Sartani, Gil; Ishay, Avraham; Luboshitzky, Rafael

    2013-04-01

    To evaluate the pituitary-adrenal axis function by means of the adrenocorticotropic hormone (ACTH) stimulation test following a single intravitreal injection of triamcinolone acetonide (IVTA). Prospective comparative clinical interventional study. Twenty-eight patients (28 eyes) received a single IVTA (4 mg in 0.1 ml) for macular edema. The basal cortisol level and the response to 1 μg adrenocorticotropic hormone stimulation were determined on the morning before IVTA injection and at 1 day and 1, 2, and 4 weeks after IVTA injection. Results were compared with those obtained from a control group of 50 healthy subjects. All patients in the study had normal basal cortisol and normal response to ACTH challenge before receiving IVTA. 1 day following IVTA, basal cortisol was suppressed in one patient in the study group. Fasting serum cortisol levels at 1, 2, and 4 weeks after IVTA injection were normal in all patients in the study group. 1 day following IVTA, the peak response to ACTH at 30 min was blunted in four patients (14.3 % of the study group, p = 0.05) and the cortisol response at 60 min was suppressed (p = 0.009). 1 week following IVTA, the response to ACTH challenge was blunted in only one patient. A single IVTA injection may be associated with impaired hypothalamic-pituitary-adrenal function in some patients during the first 24 h following IVTA.

  14. Routes for Drug Delivery to the Eye and Retina: Intravitreal Injections.

    PubMed

    Meyer, Carsten H; Krohne, Tim U; Charbel Issa, Peter; Liu, Zengping; Holz, Frank G

    2016-01-01

    The advantage of intravitreal injections is an immediate and increased therapeutic effect in the intended retinal tissue. The accuracy, precision and reproducibility of the delivered volume depend on the size of the syringe and the physician's manual experience. The eyelids and eyelashes are usually disinfected using a povidone-iodine solution (10%); a sterile speculum is placed and drops of povidone-iodine (5%) are applied. The use of adequate anesthetic topical lidocaine 2% is required. The injection site should be located 3.5-4 mm posterior to the limbus. The angle of the incision through the sclera may be directed in an oblique fashion of 30°. The diameter of the needle should be smaller than 25 G, and the injected volume should be limited to 0.15 ml without a routine paracentesis. The incidence of lens injury is 0.006% (2/32,318) and 0.013% (5/35,942) for rhegmatogenous retinal detachments. The rate of suspected endophthalmitis is 0.018% after bevacizumab and 0.027% after ranibizumab injections. Sterile inflammations have been observed after Avastin injections. The concentrations of vascular endothelial growth factor inhibitors decline in a monoexponential fashion. The half-life of unbound bevacizumab is 9.82 days and that of ranibizumab 7.19 days.

  15. Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection

    PubMed Central

    Wassmer, Sarah J.; Carvalho, Livia S.; György, Bence; Vandenberghe, Luk H.; Maguire, Casey A.

    2017-01-01

    Widespread gene transfer to the retina is challenging as it requires vector systems to overcome physical and biochemical barriers to enter and diffuse throughout retinal tissue. We investigated whether exosome-associated adeno-associated virus, (exo-AAV) enabled broad retinal targeting following intravitreal (IVT) injection, as exosomes have been shown to traverse biological barriers and mediate widespread distribution upon systemic injection. We packaged an AAV genome encoding green fluorescent protein (GFP) into conventional AAV2 and exo-AAV2 vectors. Vectors were IVT injected into the eyes of adult mice. GFP expression was noninvasively monitored by fundus imaging and retinal expression was analyzed 4 weeks post-injection by qRT-PCR and histology. Exo-AAV2 outperformed conventional AAV2 in GFP expression based on fundus image analysis and qRT-PCR. Exo-AAV2 demonstrated deeper penetration in the retina, efficiently reaching the inner nuclear and outer plexiform, and to a lesser extent the outer nuclear layer. Cell targets were ganglion cells, bipolar cells, Müller cells, and photoreceptors. Exo-AAV2 serves as a robust gene delivery tool for murine retina, and the simplicity of production and isolation should make it widely applicable to basic research of the eye. PMID:28361998

  16. Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection.

    PubMed

    Wassmer, Sarah J; Carvalho, Livia S; György, Bence; Vandenberghe, Luk H; Maguire, Casey A

    2017-03-31

    Widespread gene transfer to the retina is challenging as it requires vector systems to overcome physical and biochemical barriers to enter and diffuse throughout retinal tissue. We investigated whether exosome-associated adeno-associated virus, (exo-AAV) enabled broad retinal targeting following intravitreal (IVT) injection, as exosomes have been shown to traverse biological barriers and mediate widespread distribution upon systemic injection. We packaged an AAV genome encoding green fluorescent protein (GFP) into conventional AAV2 and exo-AAV2 vectors. Vectors were IVT injected into the eyes of adult mice. GFP expression was noninvasively monitored by fundus imaging and retinal expression was analyzed 4 weeks post-injection by qRT-PCR and histology. Exo-AAV2 outperformed conventional AAV2 in GFP expression based on fundus image analysis and qRT-PCR. Exo-AAV2 demonstrated deeper penetration in the retina, efficiently reaching the inner nuclear and outer plexiform, and to a lesser extent the outer nuclear layer. Cell targets were ganglion cells, bipolar cells, Müller cells, and photoreceptors. Exo-AAV2 serves as a robust gene delivery tool for murine retina, and the simplicity of production and isolation should make it widely applicable to basic research of the eye.

  17. Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits.

    PubMed

    García-Caballero, Cristina; Prieto-Calvo, Esther; Checa-Casalengua, Patricia; García-Martín, Elena; Polo-Llorens, Vicente; García-Feijoo, Julián; Molina-Martínez, Irene Teresa; Bravo-Osuna, Irene; Herrero-Vanrell, Rocío

    2017-03-01

    Local long-term delivery of glial cell line derived neurotrophic factor (GDNF) from vitamin E/poly-lactic-co-glycolic acid microspheres (MSs) protects retinal ganglion cells in an animal model of glaucoma for up to 11weeks. However, the pharmacokinetics of GDNF after intravitreal injection of MSs is not known. We evaluated the GDNF levels after a single intravitreal injection of GDNF/VitE MSs. Biodegradable MSs were prepared by the solid-oil-in-water emulsion-solvent evaporation technique and characterized. Rabbits received a single intravitreal injection (50μL) of GDNF/VitE MSs (4%w/v; 24 right eyes; 74.85ng GDNF), blank MSs (4%w/v; 24 left eyes), and balanced salt solution (4 eyes). Two controls eyes received no injections. At 24h, 1, 4, 6, 8, 12, 18, and 24weeks after injection, the eyes were enucleated, and the intravitreal GDNF levels were quantified. Pharmacokinetic data were analysed according to non-compartmental model. Intraocular GDNF levels of 717.1±145.1pg/mL were observed at 24h for GDNF-loaded MSs, followed by a plateau (745.3±25.5pg/mL) until day 28. After that, a second plateau (17.4±3.7pg/mL) occurred from 8 to 24weeks post-injection, significantly higher than the basal levels. Eyes injected with GDNF/vitE and Blank-MSs did not show any abnormalities during the six-months follow up after administration. The single injection of GDNF/VitE MSs provided a sustained controlled release of the neurotrophic factor in a controlled fashion for up to six months.

  18. Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

    PubMed

    Shin, Yong Un; Hong, Eun Hee; Lim, Han Woong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon

    2017-10-03

    To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. After three months, HEs area was reduced to 52.9 ± 4.21% (P < 0.001) in the triamcinolone group, 63.6 ± 6.08% (P = 0.002) in the dexamethasone implant group, and 85.2 ± 5.07% (P = 0.198) in the bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P < 0.001) and at two months in the dexamethasone implant group (70.1 ± 5.21%, P = 0.039). Our study suggests intravitreal steroids (triamcinolone, dexamethasone implants) significantly reduce HEs in DME patients on short-term follow-up, whereas intravitreal bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

  19. High Variation of Intravitreal Injection Rates and Medicare Anti-Vascular Endothelial Growth Factor Payments per Injection in the United States.

    PubMed

    Erie, Jay C; Barkmeier, Andrew J; Hodge, David O; Mahr, Michael A

    2016-06-01

    To estimate geographic variation of intravitreal injection rates and Medicare anti-vascular endothelial growth factor (VEGF) drug costs per injection in aging Americans. Observational cohort study using 2013 Medicare claims database. United States fee-for-service (FFS) Part B Medicare beneficiaries and their providers. Medicare Provider Utilization and Payment Data furnished by the Centers for Medicare and Medicaid Services was used to identify all intravitreal injection claims and anti-VEGF drug claims among FFS Medicare beneficiaries in all 50 states and the District of Columbia in 2013. The rate of FFS Medicare beneficiaries receiving intravitreal injections and the mean Medicare-allowed drug payment per anti-VEGF injection was calculated nationally and for each state. Geographic variations were evaluated by using extremal quotient, coefficient of variation, and systematic component of variance (SCV). Rate of FFS Medicare Part B beneficiaries receiving intravitreal injections (Current Procedural Terminology [CPT] code, 67028), nationally and by state; mean Medicare-allowed drug payment per anti-VEGF injection (CPT code, 67028; and treatment-specific J-codes, J0178, J2778, J9035, J3490, and J3590) nationally and by state. In 2013, the rate of FFS Medicare beneficiaries receiving intravitreal injections varied widely by 7-fold across states (range by state, 4 per 1000 [Wyoming]-28 per 1000 [Utah]), averaging 19 per 1000 beneficiaries. The mean SCV was 8.5, confirming high nonrandom geographic variation. There were more than 2.1 million anti-VEGF drug claims, totaling more than $2.3 billion in Medicare payments for anti-VEGF agents in 2013. The mean national Medicare drug payment per anti-VEGF injection varied widely by 6.2-fold across states (range by state, $242 [South Carolina]-$1509 [Maine]), averaging $1078 per injection. Nationally, 94% of injections were office based and 6% were facility based. High variation was observed in intravitreal injection rates and

  20. Electroretinographic evaluations of retinal function before, just after, and after intravitreal injections

    PubMed Central

    Yagura, Kazuma; Shinoda, Kei; Matsumoto, Soiti; Terauchi, Gaku; Kawashima, Makoto; Watanabe, Emiko; Matsumoto, Harue; Iwata, Takeshi; Mizota, Atsushi; Miyake, Yozo

    2016-01-01

    Intravitreal injections (IVI) have become a part of daily practice for a growing number of procedures. We evaluated the retinal function by recording intraoperative photopic electroretinograms (ERGs) before an injection (T1), just after the injection (T2), and after the aspiration of the anterior chamber fluid (T3) of 19 eyes of 19 patients (mean age 70.6 years; men = 11) who received an IVI of an anti-vascular endothelial growth factor. The mean amplitudes of the b-wave, photopic negative responses (PhNR), and oscillatory potentials (OPs) 1 and 2 at T2 were significantly smaller than that at T1, but no significant difference was observed between T3 and T1. The mean implicit times of the a-wave and OP1, 2, and 3 at T2 and the a-wave and the OP2 at T3 were significantly longer than that at T1. The mean intraocular pressure (IOP) at T2 (49.32 mm Hg) was significantly higher and the IOP at T3 (8.74 mm Hg) was significantly lower than that at T1 (21.05 mm Hg). The retinal function was reduced and the IOP elevated just after the IVI. The response of each ERG component was different suggesting a different sensitivity of each type of retinal neuron to IVI. PMID:27492923

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

    PubMed Central

    Ataş, Mustafa; Başkan, Burhan; Özköse, Ayşe; Mutlu Sarıgüzel, Fatma; Demircan, Süleyman; Pangal, Emine

    2014-01-01

    AIM To evaluate the effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections. METHODS Seventy-two eyes of 36 patients [36 eyes in control group, 36 eyes in intravitreal injection (IVI) group] were enrolled in the study. All the eyes had at least one IVI and had diabetic macular edema (DME) or age-related macular degeneration (ARMD). Moxifloxacin was prescribed to all the patients four times a day for five days following injection. Conjunctival cultures were obtained from the lower fornix via standardized technique with every possible effort made to minimize contamination from the lids, lashes, or skin. Before the application of any ophthalmic medication, conjunctival cultures were obtained from both eyes using sterile cotton culture. An automated microbiology system was used to identify the growing bacteria and determine antibiotic sensitivity. RESULTS The bacterial cultures were isolated from 72 eyes of 36 patients, sixteen of whom patients (44.4%) were male and twenty (55.6%) were female. Average age was 68.4±9.0 (range 50-86). The average number of injections before taking cultures was 3.1+1.0. Forty-eight (66.7%) of 72 eyes had at least one significant organism. There was no bacterial growth in 8 (20.5%) of IVI eyes and in 16 (44.4%) of control eyes (P=0.03). Of the bacteria isolated from culture, 53.8% of coagulase negative staphylococci (CoNS) in IVI eyes and 47.2% CoNS in control eyes. This difference between IVI eyes and control eyes about bacteria isolated from culture was not statistically significant (P=0.2). Eleven of 25 bacteria (44.0%) isolated from IVI eyes and 11 (57.9%) of 19 bacteria isolated from control eyes were resistant to oxacillin. The difference in frequency of moxifloxacine resistance between two groups was not statistically significant (12.0% in IVI eyes and 21.1% in control eyes) (P=0.44). There were no cases of resistance to vancomycin, teicoplanin and

  2. Antibacterial properties of 2% lidocaine and reduced rate of endophthalmitis after intravitreal injection.

    PubMed

    Tustin, Aaron; Kim, Stephen J; Chomsky, Amy; Hubbard, G Baker; Sheng, Jinsong

    2014-05-01

    To determine whether the application of subconjunctival 2% lidocaine/0.1% methylparaben for anesthesia may reduce rates of endophthalmitis after intravitreal (IVT) injection. We performed in vitro experiments to determine the antibacterial properties of 2% lidocaine/0.1% methylparaben (lidocaine) against causative organisms of endophthalmitis. Isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans from patients with endophthalmitis were incubated with or without lidocaine. Aliquots (100 µL) were plated on Mueller-Hinton (S. aureus and S. epidermidis) or blood agar plates (S. viridans) at 0, 10, 30, 120, and 240 minutes, and colonies were counted after 24 hours. A retrospective review of 15,042 IVT injections was performed from January 2004 to February 2011 to determine the rate of endophthalmitis with or without application of subconjunctival lidocaine for anesthesia. Lidocaine demonstrated rapid bactericidal effects against all 3 organisms. After 10 minutes of exposure, there was approximately a 90% (P < 0.01), 95% (P < 0.001), and 92% (P < 0.001) reduction in colony forming units when compared with time 0 for S. aureus, S. epidermidis, and S. viridans, respectively. Complete elimination of colony forming units occurred at subsequent time points for each organism in contrast to logarithmic increase for control plates. There were a total of 0 cases of endophthalmitis of 6,853 IVT injections performed with subconjunctival lidocaine and 8 cases of endophthalmitis of 8,189 (0.1%) IVT injections performed with other methods of anesthesia (P = 0.03). Application of subconjunctival 2% lidocaine/0.1% methylparaben for anesthesia may reduce the incidence of endophthalmitis after IVT injection.

  3. Repeated intravitreous ranibizumab injections for diabetic macular edema and the risk of sustained elevation of intraocular pressure or the need for ocular hypotensive treatment.

    PubMed

    Bressler, Susan B; Almukhtar, Talat; Bhorade, Anjali; Bressler, Neil M; Glassman, Adam R; Huang, Suber S; Jampol, Lee M; Kim, Judy E; Melia, Michele

    2015-05-01

    For the management of retinal disease, the use of intravitreous injections of anti-vascular endothelial growth factor has increased. Recent reports have suggested that this therapy may cause sustained elevation of intraocular pressure (IOP) and may potentially increase the risk of glaucoma for patients with retinal disease. To assess the risk of sustained IOP elevation or the need for IOP-lowering treatments for eyes with diabetic macular edema following repeated intravitreous injections of ranibizumab. An exploratory analysis was conducted within a Diabetic Retinopathy Clinical Research Network randomized clinical trial. Study enrollment dates were from March 20, 2007, to December 17, 2008. Of 582 eyes (of 486 participants) with center-involved diabetic macular edema and no preexisting open-angle glaucoma, 260 were randomly assigned to receive a sham injection plus focal/grid laser treatment, and 322 were randomly assigned to receive ranibizumab plus deferred or prompt focal/grid laser treatment. The cumulative probability of sustained IOP elevation, defined as IOP of at least 22 mm Hg and an increase of at least 6 mm Hg from baseline at 2 consecutive visits, or the initiation or augmentation of ocular hypotensive therapy, through 3 years of follow-up. The mean (SD) baseline IOP in both treatment groups was 16 (3) mm Hg (range, 5-24 mm Hg). The cumulative probability of sustained IOP elevation or of initiation or augmentation of ocular hypotensive therapy by 3 years, after repeated ranibizumab injections, was 9.5% for the participants who received ranibizumab plus prompt or deferred focal/grid laser treatment vs 3.4% for the participants who received a sham injection plus focal/grid laser treatment (difference, 6.1% [99% CI, -0.2% to 12.3%]; hazard ratio, 2.9 [99% CI, 1.0-7.9]; P = .01). The distribution of IOP and the change in IOP from baseline at each visit through 3 years were similar in each group. In eyes with center-involved diabetic macular edema and no

  4. Intravitreal tPA Injection and Pneumatic Displacement for Submacular Hemorrhage in a 10-Year-Old Child

    PubMed Central

    Hirose, Hiroshi; Hattori, Tomohiro

    2016-01-01

    Background. Submacular hemorrhage can occur after blunt trauma to the eye. Intravitreal tissue plasminogen activator (tPA) and gas injection are often used for treatment and are effective for submacular hemorrhage caused by age-related macular degeneration. This report describes the clinical outcome in a child with submacular hemorrhage caused by traumatic choroidal rupture who underwent successful intravitreal tPA injection and pneumatic displacement. Case Presentation. A 10-year-old boy developed sudden decrease of vision and a central scotoma in his right eye after trauma. Submacular hemorrhage was found in the eye. Visual acuity was 20/70 OD. Tissue plasminogen activator (12.5 μg in 0.05 mL) and 0.3 mL of pure sulfur hexafluoride were injected into the vitreous cavity under general anesthesia. After surgery, the patient was instructed to maintain a prone position. Displacement of the submacular hemorrhage from the fovea revealed a choroidal rupture, presumed to be the cause of the hemorrhage. After 4 months of follow-up, visual acuity was restored and final visual acuity is 20/16. Conclusion. Intravitreal tPA and gas injection can be an effective treatment for children with submacular hemorrhage. PMID:27722001

  5. Safety, sterility and stability of direct-from-vial multiple dosing intravitreal injection of bevacizumab.

    PubMed

    Das, Taraprasad; Volety, Srinivas; Ahsan, Saad M; Thakur, Abhay K; Sharma, Savitri; Padhi, Tapas R; Basu, Soumyava; Rao, Ch Mohan

    2015-07-01

    This study aims to determine the stability, sterility and safety of bevacizumab multiple dosing from a single vial without prior aliquoting. In-vitro and human study. Six bevacizumab vials, used in multiple patients on a single day by direct withdrawal from the vial, and stored in 4°C up to a variable period, were tested for stability (high-performance liquid chromatography; [HPLC]), sterility (culture), conformational stability by circular dichroism and fluorescence spectroscopy and the rubber cork structural integrity (electron microscopy [EM]). HPLC of all six samples of used bevacizumab and the control bevacizumab sample were similar; culture was negative; and the EM of rubber corks did not show an open communication. Spectroscopic studies indicated drug conformational stability. Further, there was no infection or inflammation in 221 consecutive patients (973 injections) when bevacizumab was stored at 4°C and used for one week. Bevacizumab does not lose stability when stored at 4°C. It may be used for a week by direct withdrawal from the vial without fear of infection or inflammation if all standard precautions related to intravitreal injection are adhered to. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

  6. Restoration of foveal photoreceptors after intravitreal ranibizumab injections for diabetic macular edema

    PubMed Central

    Mori, Yuki; Suzuma, Kiyoshi; Uji, Akihito; Ishihara, Kenji; Yoshitake, Shin; Fujimoto, Masahiro; Dodo, Yoko; Yoshitake, Tatsuya; Miwa, Yuko; Murakami, Tomoaki

    2016-01-01

    Anti-vascular endothelial growth factor drugs are the first-line treatment for diabetic macular edema (DME), although the mechanism of the visual acuity (VA) improvement remains largely unknown. The association between photoreceptor damage and visual impairment encouraged us to retrospectively investigate the changes in the foveal photoreceptors in the external limiting membrane (ELM) and ellipsoid zone (EZ) on spectral-domain optical coherence tomography (SD-OCT) images in 62 eyes with DME treated with intravitreal ranibizumab (IVR) injections. The transverse lengths of the disrupted EZ and ELM were shortened significantly (P < 0.001 and P = 0.044, respectively) at 12 months. The qualitative investigation also showed restoration of the EZ and ELM lines on SD-OCT images. The EZ at 12 months lengthened in 34 of 38 eyes with discontinuous EZ and was preserved in 16 of 21 eyes with complete EZ at baseline. VA improvement was positively correlated with shortening of the disrupted EZ at 12 months (ρ = 0.463, P < 0.001), whereas the decrease in central subfield thickness was associated with neither VA improvement nor changes in EZ status (ρ = 0.215, P = 0.093 and (ρ = 0.209, P = 0.103, respectively). These data suggested that photoreceptor restoration contributes to VA improvement after pro re nata treatment with IVR injections for DME independent of resolved retinal thickening. PMID:27966644

  7. Mobile ultra-clean unidirectional airflow screen reduces air contamination in a simulated setting for intra-vitreal injection.

    PubMed

    Lapid-Gortzak, Ruth; Traversari, Roberto; van der Linden, Jan Willem; Lesnik Oberstein, Sarit Y; Lapid, Oren; Schlingemann, Reinier O

    2017-02-01

    The aim of this study is to determine whether the use of a mobile ultra-clean laminar airflow screen reduces the air-borne particle counts in the setting of a simulated procedure of an intra-vitreal injection. A mobile ultra-clean unidirectional airflow (UDF) screen was tested in a simulated procedure for intra-vitreal injections in a treatment room without mechanical ventilation. One UDF was passed over the instrument tray and the surgical area. The concentration of particles was measured in the background, over the instrument table, and next to the ocular area. The degree of protection was calculated at the instrument table and at the surgical site. Use of the UDF mobile screen reduced the mean particle concentration (particles > 0.3 microns) on the instrument table by a factor of at least 100.000 (p < 0.05), and over the patient's eye by at least a factor of 436 (p < 0.05), which in clinical practice translates into significantly reduced air contamination. Mobile UDF screen reduces the mean particle concentration substantially. The mobile UDF screen may therefore allow for a safer procedural environment for ambulatory care procedures such as intra-vitreal injections in treatment rooms.

  8. Development of ocular hypertension and persistent glaucoma after intravitreal injection of triamcinolone

    PubMed Central

    Kocabora, M Selim; Yilmazli, Cemil; Taskapili, Muhittin; Gulkilik, Gokhan; Durmaz, Sahan

    2008-01-01

    Purpose This study evaluates intraocular pressure (IOP) elevation secondary to intravitreal injection of triamcinolone acetonide (IVTA) and discusses its management. Methods The records of 175 patients who underwent IVTA treatment and regular eye examinations in the period 2003–2006 were reviewed. One hundred and twenty-two of these patients were included in the study, of which 147 eyes that received IVTA (4 mg/0.1 ml) were followed for at least 9 months. Mean IOPs observed after IVTA injection as well as IOP elevations defined as moderate (≥5 mm Hg), important (≥10 mm Hg) and severe (>25 mm Hg) during the follow-up period were evaluated and compared statistically. Results Overall, the mean IOPs following IVTA injection were statistically significantly higher than the preinjection IOP (15.8 ± 2.6), after the first hour (17.7 ± 2.9), the first week (18.7 ± 4.1), the first month (19.6 ± 6.2), the second month (19.1 ± 6.1), the third month (18.0 ± 4.1), the sixth month (17.3 ± 4.0), and the ninth month (17.0 ± 2.7), but not after the first day (16.3 ± 7.6). Important IOP elevations were observed mostly in the first (17.7%) and second months (10.2%). In 40 (27.7%) eyes, topical antiglaucomatous therapy was needed and 7 later required surgical intervention to lower the IOP. Of the remaining 33 eyes, topical treatment was continued in 14 (9.5%) because of IOPs ≥20 mm Hg. Conclusion The persistence of IOP elevation beyond the IVTA clearance period and the development of intractable secondary glaucoma requiring surgical intervention substantiate the need for careful consideration of IVTA indication and follow-up. PMID:19668401

  9. Assessment of Corneal Sensation, Innervation and Retinal Nerve Fiber Layer in Patients Treated with Multiple Intravitreal Ranibizumab Injections

    PubMed Central

    Belviranli, Selman; Malik, Rayaz A.; Kerimoglu, Hurkan; Satirtav, Gunhal; Zengin, Nazmi

    2017-01-01

    Purpose To evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD). Methods Sixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects. Results The mean number of ranibizumab injections per eye was 8.9±5.0 (range 3–20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P = 0.237), and the eyes of healthy control subjects (P = 0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters. Conclusions Multiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD. PMID:28085965

  10. The effect of intravitreal injections on dry eye, and proposed management strategies

    PubMed Central

    Laude, Augustinus; Lim, Jimmy WK; Srinagesh, Vishwanath; Tong, Louis

    2017-01-01

    Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents has become a commonly used treatment method for a number of ophthalmic conditions, including age-related macular degeneration. Although anti-VEGF therapy has shown promising results for many patients, there are several aspects of its application that have not been thoroughly investigated. One of these is the development and/or escalation of concurrent dry eye syndrome. Many patients undergoing treatment are already predisposed to dry eye disease due to their age and overall ocular health. As dry eye can have a substantial impact on quality of life, it has become increasingly apparent that the clinical signs and symptoms should be closely monitored and aggressively managed. This will allow for the optimization of patient comfort and visual potential. Here, we discuss the reasons why dry eye may develop during the course of repeated ocular anti-VEGF therapy, highlighting the key concerns about current practices and proposing possible solutions to improve the outcome for the patients. PMID:28860698

  11. Choroidal thickness and choroidal blood flow after intravitreal bevacizumab injection in eyes with central serous chorioretinopathy.

    PubMed

    Okamoto, Masahiro; Matsuura, Toyoaki; Ogata, Nahoko

    2015-01-01

    To quantitatively evaluate choroidal thickness (CT) and choroidal blood flow in the subfoveal region after intravitreal bevacizumab injection (IVB) for the treatment of chronic central serous chorioretinopathy (CSC). Prospective, comparative study of 20 eyes with chronic CSC and and 20 fellow eyes treated with 1.25 mg/0.05 mL IVB. Subfoveal CT and serous retinal detachment height were measured using enhanced depth imaging optical coherence tomography. Subfoveal choroidal blood flow was assessed by the mean blur rate of laser speckle flowgraphy. IOP, blood pressure, and pulse rate, and ocular perfusion pressure were also measured. All measurements were made before and after IVB. Subfoveal fluid was not present after IVB in the affected eyes. The mean subfoveal CT decreased from 335 µm at baseline to 304 and 291 µm at 1 and 3 months, respectively, after IVB. Average mean blur rate ratio decreased from baseline to 92.9% and 88.0% at 1 and 3 months, respectively. In the fellow eyes, subfoveal CT and choroidal blood flow decreased slightly from baseline. There was a significant correlation between the decrease in subfoveal CT and choroidal blood flow after IVB in affected eyes. IOP, mean arterial pressure, pulse rate, and ocular perfusion pressure did not change significantly after IVB. IVB significantly reduced subfoveal CT, choroidal blood flow, and subretinal fluid absorption in eyes with chronic CSC. The reduction of subfoveal CT after IVB was likely caused by the reduction of subfoveal choroidal blood flow. Copyright 2015, SLACK Incorporated.

  12. Reducing oral flora contamination of intravitreal injections with face mask or silence.

    PubMed

    Doshi, Rishi R; Leng, Theodore; Fung, Anne E

    2012-03-01

    To provide experimental evidence to support or refute the proposition that the use of surgical face masks and/or avoidance of talking can decrease the dispersion of respiratory flora during an intravitreal injection. Ten surgeons recited a 30-second standardized script with blood agar plates positioned 30 cm below their mouths. The plates were divided into 4 groups, with 10 plates per group. In Group 1, participants did not wear a face mask. In Group 2, participants wore a standard surgical mask. In Group 3, no mask was worn, but plates were pretreated with 5% povidone-iodine. In Group 4, no mask was worn, and participants remained silent for 30 seconds. The plates were then incubated at 37°C for 24 hours, and the number of colony-forming units (CFUs) was determined. Mean bacterial growth were as follows: Group 1, 8.6 CFUs per subject; Group 2, 1.1 CFUs per subject; Group 3, 0.1 CFUs per subject; and Group 4, 2.4 CFUs per subject. Differences between the groups were statistically significant (P < 0.05), with the exception of Group 2 versus Group 4 (P = 0.115). The use of a face mask and avoidance of talking each significantly decreased the dispersion of bacteria. Even without these interventions, plates pretreated with povidone-iodine demonstrated the least bacterial growth.

  13. Catalytic Nanoceria Are Preferentially Retained in the Rat Retina and Are Not Cytotoxic after Intravitreal Injection

    PubMed Central

    Wong, Lily L.; Hirst, Suzanne M.; Pye, Quentin N.; Reilly, Christopher M.; Seal, Sudipta; McGinnis, James F.

    2013-01-01

    Cerium oxide nanoparticles (nanoceria) possess catalytic and regenerative radical scavenging activities. The ability of nanoceria to maintain cellular redox balance makes them ideal candidates for treatment of retinal diseases whose development is tightly associated with oxidative damage. We have demonstrated that our stable water-dispersed nanoceria delay photoreceptor cell degeneration in rodent models and prevent pathological retinal neovascularization in vldlr mutant mice. The objectives of the current study were to determine the temporal and spatial distributions of nanoceria after a single intravitreal injection, and to determine if nanoceria had any toxic effects in healthy rat retinas. Using inductively-coupled plasma mass spectrometry (ICP-MS), we discovered that nanoceria were rapidly taken up by the retina and were preferentially retained in this tissue even after 120 days. We also did not observe any acute or long-term negative effects of nanoceria on retinal function or cytoarchitecture even after this long-term exposure. Because nanoceria are effective at low dosages, nontoxic and are retained in the retina for extended periods, we conclude that nanoceria are promising ophthalmic therapeutics for treating retinal diseases known to involve oxidative stress in their pathogeneses. PMID:23536794

  14. The effect of intravitreal injections on dry eye, and proposed management strategies.

    PubMed

    Laude, Augustinus; Lim, Jimmy Wk; Srinagesh, Vishwanath; Tong, Louis

    2017-01-01

    Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents has become a commonly used treatment method for a number of ophthalmic conditions, including age-related macular degeneration. Although anti-VEGF therapy has shown promising results for many patients, there are several aspects of its application that have not been thoroughly investigated. One of these is the development and/or escalation of concurrent dry eye syndrome. Many patients undergoing treatment are already predisposed to dry eye disease due to their age and overall ocular health. As dry eye can have a substantial impact on quality of life, it has become increasingly apparent that the clinical signs and symptoms should be closely monitored and aggressively managed. This will allow for the optimization of patient comfort and visual potential. Here, we discuss the reasons why dry eye may develop during the course of repeated ocular anti-VEGF therapy, highlighting the key concerns about current practices and proposing possible solutions to improve the outcome for the patients.

  15. Intravitreal Injection of Bevacizumab for Retinopathy of Prematurity in an Infant with Peters Anomaly

    PubMed Central

    Minami, Tsuyoshi; Kuniyoshi, Kazuki; Kusaka, Shunji; Sugioka, Koji; Sakuramoto, Hiroyuki; Sakamoto, Masuo; Izu, Akane; Wada, Norihisa; Shimomura, Yoshikazu

    2014-01-01

    Purpose To report our findings in an infant with Peters anomaly type II whose retinopathy of prematurity (ROP) was treated with an anti-VEGF agent and surgeries. Case Report A male infant weighing 548 g was born prematurely at 23 weeks and 1 day with corneal opacity and shallow anterior chambers in both eyes. At the postmenstrual age of 35 weeks and 3 days, the infant was tentatively diagnosed with stage 3 ROP because of a dilated tunica vasculosa lentis and ultrasonographic findings. The boy was treated with bilateral intravitreal injections of bevacizumab (IVB) because laser photocoagulation of the retina could not be performed due to the corneal opacity. The retina in the right eye detached 3 times, namely 5 days, 16 days, and 7 months after the IVB; encircling the scleral buckle and a vitrectomy with endolaser photocoagulation were therefore required. In his left eye, the retina was reattached after the initial IVB, and no additional treatment was required. ROP was not reactivated in both eyes until the last examination at the age of 2 years and 6 months. Conclusions Our results showed that IVB is a useful treatment for ROP in patients with Peters anomaly. However, a retinal detachment can be a complication after IVB. The optimal timing of IVB for ROP in infants with hazy media needs to be determined. PMID:25408672

  16. Multiple Intravitreal Ranibizumab Injections for Persistant Choroidal Neovascularization Associated with Presumed Ocular Histoplasmosis Syndrome

    PubMed Central

    Yılmaz, Turgut; Dikci, Seyhan; Genç, Oğuzhan; Mutlu, Kayhan

    2017-01-01

    Presumed ocular histoplasmosis syndrome (POHS) is a clinical entity that is characterized by small, round, discrete, macular or mid peripheral atrophic (punched out) chorioretinal lesions (histo spots), peripapillary scarring, choroidal neovascularization (CNV), and the absence of anterior uveitis and vitritis. Diagnosis of this disorder is based upon characteristic clinical findings and a positive histoplasmin skin test or residence in an endemic region for Histoplasma capsulatum. There is no active systemic disease during diagnosis of POHS. Disciform scarring and macular CNV secondary to POHS is a well-known complication which leads to loss of visual acuity or visual disturbance. Without therapy, the visual prognosis in these patients is unfavorable. Submacular surgery, radiation, steroids, photodynamic therapy, and most recently anti-vascular endothelial growth factor therapy are current therapeutic options for this condition. We report a case with persistent CNV secondary to POHS in a middle-aged woman with moderate myopia and the clinical course of treatment with multiple intravitreal ranibizumab (Lucentis®, Novartis) injections. PMID:28405488

  17. Flicker electroretinograms before and after intravitreal ranibizumab injection in eyes with central retinal vein occlusion.

    PubMed

    Yasuda, Shunsuke; Kachi, Shu; Ueno, Shinji; Piao, Chang-Hua; Terasaki, Hiroko

    2015-09-01

    To compare the amplitudes and implicit times of the flicker electroretinograms before and after an intravitreal injection of ranibizumab (IVR) in eyes with a central retinal vein occlusion (CRVO). We reviewed the medical records of 15 consecutive patients who had macular oedema secondary to CRVO and had received an IVR at the Nagoya University Hospital from November 2013 to July 2014. Flicker ERGs were recorded with both the RETeval(™) system and a conventional ERG system before the IVR. One month after the IVR, recordings were repeated with only the RETeval(™) system. The mean implicit times of the flicker ERGs of the affected eyes recorded with the RETeval(™) system were significantly longer than that of the fellow eyes (32.2 ± 2.6 msec versus 28.1 ± 1.2 msec, p < 0.001). One month after the IVR, the implicit times of the flicker ERGs of affected eyes were significantly shortened from 32.2 ± 2.6 to 30.6 ± 2.2 msec (p < 0.001). The shortening of the implicit times of the flicker ERGs after the IVR indicates an improvement of retinal function after anti-VEGF therapy for CRVO eyes. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  18. Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial.

    PubMed

    Bressler, Susan B; Qin, Haijing; Melia, Michele; Bressler, Neil M; Beck, Roy W; Chan, Clement K; Grover, Sandeep; Miller, David G

    2013-08-01

    The standard care for proliferative diabetic retinopathy (PDR) usually is panretinal photocoagulation, an inherently destructive treatment that can cause iatrogenic vision loss. Therefore, evaluating the effects of therapies for diabetic macular edema on development or worsening of PDR might lead to new therapies for PDR. To evaluate the effects of intravitreal ranibizumab or triamcinolone acetonide, administered to treat diabetic macular edema, on worsening of diabetic retinopathy. Exploratory analysis was performed on worsening of retinopathy, defined as 1 or more of the following: (1) worsening from no PDR to PDR, (2) worsening of 2 or more severity levels on reading center assessment of fundus photographs in eyes without PDR at baseline, (3) having panretinal photocoagulation, (4) experiencing vitreous hemorrhage, or (5) undergoing vitrectomy for the treatment of PDR. Community- and university-based ophthalmology practices. Individuals with central-involved diabetic macular edema causing visual acuity impairment. Eyes were assigned randomly to sham with prompt focal/grid laser, 0.5 mg of intravitreal ranibizumab with prompt or deferred (≥24 weeks) laser, or 4 mg of intravitreal triamcinolone acetonide with prompt laser. Three-year cumulative probabilities for retinopathy worsening. For eyes without PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening (P value comparison with sham with prompt laser) were 23% using sham with prompt laser, 18% with ranibizumab with prompt laser (P = .25), 7% with ranibizumab with deferred laser (P = .001), and 37% with triamcinolone with prompt laser (P = .10). For eyes with PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening were 40%, 21% (P = .05), 18% (P = .02), and 12% (P < .001), respectively. CONCLUSIONS AND RELEVANCE Intravitreal ranibizumab appears to be associated with a reduced risk of diabetic retinopathy worsening in eyes with or without PDR. Intravitreal

  19. Bilateral Retinal Detachments After Intravitreal Injection of Adipose-Derived 'Stem Cells' in a Patient With Exudative Macular Degeneration.

    PubMed

    Saraf, Steven S; Cunningham, Matthew A; Kuriyan, Ajay E; Read, Sarah P; Rosenfeld, Philip J; Flynn, Harry W; Albini, Thomas A

    2017-09-01

    A 77-year-old woman with exudative macular degeneration underwent bilateral intravitreal injections of "stem cells" at a clinic in Georgia. One month and 3 months after injection, she developed retinal detachments in the left and right eyes, respectively. Increased awareness within the medical community of such poor outcomes is critical so that clinics offering untested practices that have been shown to be potentially harmful to patients can be identified and brought under U.S. Food and Drug Administration oversight. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:772-775.]. © 2017 [Saraf, Cunningham, Kuriyan, et al.].

  20. Effectiveness of Intravitreal Injection of Ranibizumab for Neovascular Age-Related Macular Degeneration with Serous Pigment Epithelial Detachment

    PubMed Central

    Zhao, Chun; Zhang, Zhen; Chen, Lei; Wang, Fang; Xu, Ding

    2016-01-01

    Background We sought to observe the effectiveness of intravitreal injection of ranibizumab in treating neovascular age-related macular degeneration (nAMD) with serous pigment epithelial detachment (sPED). Material/Methods A retrospective, noncomparative case series was performed. Twenty-3 eyes of 23 patients with sPED secondary to nAMD who had received intravitreal injections of ranibizumab were included in this study. All patients underwent best-corrected visual acuity (BCVA), synchronous fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) examinations. All patients were treated with pro re nata intravitreal injections after 3 loading doses of ranibizumab and were followed up for 12 months. The differences in the BCVAs, maximum PED heights, PED volumes and CFTs of the affected eyes were compared between the baseline and last visit. Results Twelve months after the first injection, improved visual acuity was observed in 16 of the 23 eyes. 4 eyes exhibited stable visual acuity, and 3 eyes exhibited impaired visual acuity. The mean post-injection logMAR BCVA was 0.58±0.05, which was much better than that at baseline (0.76±0.08; t=1.751, P=0.0869). The mean maximum PED height at baseline was 350.17±35.73μm and it was decreased to 238.87±36.87μm (t=2.192, P=0.0337) at the last visit. The mean PED volume after injection was 0.34±0.1 mm3, which was significantly decreased compared with that at baseline (0.81±0.21 mm3; t=2.021, P=0.0494).The mean CFT decreased, but this difference was not statistically significant (t=1.003, P=0.3211). None of the patients exhibited endophthalmitis, uveitis or RPE tears. Conclusions Intravitreal injection of ranibizumab for the treatment of neovascular age-related macular degeneration with serous pigment epithelial detachment safely and effectively improved the patients’ visual acuities and decreased their PED heights volumes. PMID:26972376

  1. Acute Hemorrhagic Retinopathy following Intravitreal Melphalan Injection for Retinoblastoma: A Report of Two Cases and Technical Modifications to Enhance the Prevention of Retinal Toxicity

    PubMed Central

    Aziz, Hassan A.; Kim, Jonathan W.; Munier, Francis L.; Berry, Jesse L.

    2017-01-01

    Aims To report the occurrence of acute hemorrhagic retinopathy following intravitreal melphalan injection for retinoblastoma. Methods This is a retrospective case series of 2 patients with retinoblastoma treated with intravitreal melphalan for vitreous seeding who developed acute hemorrhagic retinopathy. Results Patient 1 is a 6-month-old female with bilateral retinoblastoma (Group D right eye and Group B left eye) treated with 4 cycles of systemic chemotherapy and 2 intravitreal melphalan injections in each eye. Patient 2 is a 10-month-old male with unilateral Group D retinoblastoma treated with 6 cycles of systemic chemotherapy and 2 injections of intravitreal melphalan. At the 1-week follow-up after the second injection, both patients had an acute hemorrhagic retinopathy that resulted in chorioretinal toxicity with a sharp demarcation line between the normal and abnormal retina. At the last follow-up (22 and 12 months, respectively), there was total tumor control and resolution of vitreous seeding in both patients. Conclusions Although intravitreal melphalan injection is effective for vitreous seeding in eyes with retinoblastoma, acute hemorrhagic retinopathy and diffuse chorioretinal atrophy is a possible complication of this treatment modality. Given the clinical findings observed in these patients, the development of this retinal toxicity most likely results from a retrohyaloid overdose. Consequently we suggest preventive measures aimed at limiting the risk of retrohyaloid injection.

  2. The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews.

    PubMed

    Ward, Alexander H; Siegwart, John T; Frost, Michael R; Norton, Thomas T

    2016-04-01

    lntravitreal injection of substances dissolved in a vehicle solution is a common tool used to assess retinal function. We examined the effect of injection procedures (three groups) and vehicle solutions (four groups) on the development of form deprivation myopia (FDM) in juvenile tree shrews, mammals closely related to primates, starting at 24 days of visual experience (about 45 days of age). In seven groups (n = 7 per group), the myopia produced by monocular form deprivation (FD) was measured daily for 12 days during an 11-day treatment period. The FD eye was randomly selected; the contralateral eye served as an untreated control. The refractive state of both eyes was measured daily, starting just before FD began (day 1); axial component dimensions were measured on day 1 and after eleven days of treatment (day 12). Procedure groups: the myopia (treated eye - control eye refraction) in the FD group was the reference. The sham group only underwent brief daily anesthesia and opening of the conjunctiva to expose the sclera. The puncture group, in addition, had a pipette inserted daily into the vitreous. In four vehicle groups, 5 μL of vehicle was injected daily. The NaCl group received 0.85% NaCl. In the NaCl + ascorbic acid group, 1 mg/mL of ascorbic acid was added. The water group received sterile water. The water + ascorbic acid group received water with ascorbic acid (1 mg/mL). We found that the procedures associated with intravitreal injections (anesthesia, opening of the conjunctiva, and puncture of the sclera) did not significantly affect the development of FDM. However, injecting 5 μL of any of the four vehicle solutions slowed the development of FDM. NaCl had a small effect; myopia development in the last 6 days (-0.15 ± 0.08 D/day) was significantly less than in the FD group (-0.55 ± 0.06 D/day). NaCl + Ascorbic acid further slowed the development of FDM on several treatment days. H2O (-0.09 ± 0.05 D/day) and H2O + ascorbic acid

  3. Management of Acute Submacular Hemorrhage with Intravitreal Injection of Tenecteplase, Anti-vascular Endothelial Growth Factor and Gas

    PubMed Central

    Lee, Jung Pil; Park, Jun Sang; Kwon, Oh Woong; You, Yong Sung

    2016-01-01

    Purpose To evaluate the visual and anatomical outcomes for neovascular age-related macular degeneration with submacular hemorrhage after intravitreal injections of tenecteplase (TNK), anti-vascular endothelial growth factor (VEGF) and expansile gas. Methods This study was a retrospective clinical case series following 25 eyes of 25 patients. All patients received a triple injection using 0.05 mL TNK (50 µg), 0.05 mL anti-VEGF and 0.3 mL of perfluoropropane gas. Retreatment with anti-VEGF was performed as needed. Preoperative and postoperative best-corrected visual acuity and central retinal thickness were analyzed. Results The mean logarithm of the minimum angle of resolution of best-corrected visual acuity improved significantly from 1.09 ± 0.77 at baseline to 0.52 ± 0.60 at 12 months (p < 0.001). The mean central retinal thickness also improved significantly from 545 ± 156 at baseline to 266 ± 107 at 12 months (p < 0.001). A visual improvement of 0.3 logarithm of the minimum angle of resolution unit or more was achieved in 15 eyes (60%). During the 12 postoperative months, an average of 4.04 intravitreal anti-VEGF injections was applied. Conclusions A triple injection of TNK, anti-VEGF, and a gas appears to be safe and effective for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration. PMID:27247518

  4. A cluster of presumed, noninfectious endophthalmitis after intravitreal injection of bevacizumab: long-term follow-up

    PubMed Central

    Ricci, Federico; Calabrese, Antonio; De Felici, Cecilia; Missiroli, Filippo; Pileri, Marco; Regine, Federico

    2016-01-01

    Purpose To report the outcome of 5 consecutive cases of presumed, noninfectious endopththalmitis following intravitreal injection of bevacizumab (IVB). Methods Ten pre-loaded syringes of bevacizumab (1.25 mg/50 µL) furnished by a compounding pharmacy were injected intravitreally. Treatments were performed in the operating room by the same surgeon on 2 consecutive days. Results Of 10 eyes, 5 showed moderate to severe ocular inflammation within a few days of injection. All patients were treated in the same surgical session. Vitreous tap performed in the patient presenting with the most severe grade of inflammation was negative for bacteria and fungi. At the time of the vitreous biopsy, this patient was injected with vancomycin 1 mg/100 µL in the vitreous cavity. Other eyes with moderate inflammation received topical and systemic antibiotics and topical steroid treatment. Visual acuity returned to pre-endophthalmitis or better levels in all eyes within 1 month. The other 5 patients treated with IVB from the same batch in the other surgical session did not develop inflammation. Conclusions IVB can induce noninfectious endophthalmitis. The use of compounded syringes can explain clustering of the inflammation. We were unable to identify the reasons for the variable grade of inflammation we observed in our patients. PMID:27582674

  5. Predictive factors for short‐term visual outcome after intravitreal triamcinolone acetonide injection for diabetic macular oedema: an optical coherence tomography study

    PubMed Central

    Brasil, Oswaldo Ferreira Moura; Smith, Scott D; Galor, Anat; Lowder, Careen Y; Sears, Jonathan E; Kaiser, Peter K

    2007-01-01

    Aim To evaluate the predictive factors for visual outcome after intravitreal triamcinolone acetonide injection to treat refractory diabetic macular oedema (DME). Methods A retrospective chart review of patients with DME who met the following inclusion criteria was performed: clinically significant diabetic macular oedema, receipt of a 4 mg/0.1 ml intravitreal triamcinolone acetonide injection and an optical coherence tomography (OCT) of the macula performed up to 10 days before injection. All patients received a full ophthalmic examination including best‐corrected Snellen visual acuity (VA). The main outcome measure was the mean change in vision 3 months after injection. Results Data from 73 eyes of 59 patients were analysed. After a mean follow‐up of 324 days, the mean change in vision was −0.075 logarithm of minimum angle of resolution (logMAR) units, with 27.3% improving ⩾3 lines, 6.8% declining ⩾3 lines and 60.2% remaining stable within 1 line of baseline vision. Statistical analysis was performed using multivariate generalised estimating equations on the basis of data from 52 eyes of 42 patients. Factors associated with an improvement in vision 3 months after injection were worse baseline VA (−0.27 logMAR units/unit increase in baseline VA, p = 0.002) and presence of subretinal fluid (−0.17 logMAR units, p = 0.06). The presence of cystoid macular oedema negatively affected the visual outcome (0.15 logMAR units, p = 0.03). In addition, the presence of an epiretinal membrane (ERM) was associated with less visual improvement. ERM modified the effect of baseline VA as demonstrated by a significant interaction between these two variables (0.34 logMAR units/unit increase in baseline VA, p = 0.04). Conclusions OCT factors and baseline VA can be useful in predicting the outcomes of VA 3 months after intravitreal triamcinolone acetonide injection in patients with refractory DME. PMID:17108013

  6. Early clinical characteristics of bacterial endophthalmitis in retinopathy of prematurity after intravitreal bevacizumab injection: A case report

    PubMed Central

    Wang, Jianxun; Xiang, Daoman

    2017-01-01

    Intravitreal bevacizumab injection (IVB) is emerging as a safe and effective therapy for retinopathy of prematurity (ROP); however, follow-up investigations after IVB have indicated that endophthalmitis, a rare and devastating complication, may develop. The present study reports a case of an infant with ROP who developed endophthalmitis after IVB infection. The infant was administered with an intravitreal injection of broad-spectrum antibiotics to treat the endophthalmitis. A favorable anatomic outcome was achieved after follow-up. From this case, it was discovered that the early clinical characteristics of endophthalmitis infection secondary to IVB in premature infants include: i) The clinical symptoms of endophthalmitis infection appearing as early as 3–5 days after IVB; ii) a white membranous plaque on the retina surface with an obscure circular boundary; iii) a plaque that enlarges to a gray flocculent mass and intrudes the vitreous body, where the hazing surrounds the lesion; and iv) conjunctival hyperemia and cornea edema in the anterior segment of the affected eye. This case also indicated that timely retinal screening with RetCam or a binocular ophthalmoscope 3–5 days after IVB may be effective for detecting early stage endophthalmitis in infants who are unable to complain of a loss of visual acuity. From the present case report, it is advisable that the same type of screening be performed 3–5 days after other types of eye surgery, such as cataract extraction surgery, to detect early stage endophthalmitis. Furthermore, the present case also revealed that an early intravitreal injection of broad-spectrum antibiotics may be an effective treatment for premature infants with bacterial endophthalmitis. PMID:28588680

  7. Early clinical characteristics of bacterial endophthalmitis in retinopathy of prematurity after intravitreal bevacizumab injection: A case report.

    PubMed

    Wang, Jianxun; Xiang, Daoman

    2017-06-01

    Intravitreal bevacizumab injection (IVB) is emerging as a safe and effective therapy for retinopathy of prematurity (ROP); however, follow-up investigations after IVB have indicated that endophthalmitis, a rare and devastating complication, may develop. The present study reports a case of an infant with ROP who developed endophthalmitis after IVB infection. The infant was administered with an intravitreal injection of broad-spectrum antibiotics to treat the endophthalmitis. A favorable anatomic outcome was achieved after follow-up. From this case, it was discovered that the early clinical characteristics of endophthalmitis infection secondary to IVB in premature infants include: i) The clinical symptoms of endophthalmitis infection appearing as early as 3-5 days after IVB; ii) a white membranous plaque on the retina surface with an obscure circular boundary; iii) a plaque that enlarges to a gray flocculent mass and intrudes the vitreous body, where the hazing surrounds the lesion; and iv) conjunctival hyperemia and cornea edema in the anterior segment of the affected eye. This case also indicated that timely retinal screening with RetCam or a binocular ophthalmoscope 3-5 days after IVB may be effective for detecting early stage endophthalmitis in infants who are unable to complain of a loss of visual acuity. From the present case report, it is advisable that the same type of screening be performed 3-5 days after other types of eye surgery, such as cataract extraction surgery, to detect early stage endophthalmitis. Furthermore, the present case also revealed that an early intravitreal injection of broad-spectrum antibiotics may be an effective treatment for premature infants with bacterial endophthalmitis.

  8. Clinical effects and safety of treating diabetic macular edema with intravitreal injection of ranibizumab combined with retinal photocoagulation

    PubMed Central

    Yan, Panshi; Qian, Cheng; Wang, Wenzhan; Dong, Yi; Wan, Guangming; Chen, Yue

    2016-01-01

    Background This study was designed to examine the clinical effects of treating diabetic macular edema with an intravitreal injection of ranibizumab in combination with retinal photocoagulation. Methods Sixty-two cases (75 eyes) with confirmed severe proliferative diabetic retinopathy or proliferative diabetic retinopathy in combination with macular edema were randomly divided into the observation group (37 eyes were given an intravitreal injection of ranibizumab combined with retinal photocoagulation) and the control group (38 eyes received retinal photocoagulation only). Vision, fundus condition, central macular thickness, and the macular leakage area were recorded before and after treatment. Results The best-corrected visual acuity and macular leakage area were similar between the observation and control groups (P>0.05). The best-corrected visual acuity in the observation group was higher than that in the control group 3 and 6 months after treatment (P<0.05) and showed a rising tendency. The macular leakage area in the observation group was significantly lower than that in the control group 1 and 3 months after treatment (P<0.05). However, the macular leakage area was similar 6 months after treatment (P>0.05). The central macular thickness of the observation group was lower than that in the control group 1, 3, and 6 months after treatment (P<0.05). The laser energy used in the observation group was also smaller than that in the control group (P<0.05). The intraocular pressure was not significantly different between the groups (P<0.05). No patients in the two groups developed eye or systemic complications, such as glaucoma, cataract, or vitreous hemorrhage during treatment. Conclusion Intravitreal injection of ranibizumab combined with retinal photocoagulation was proven to be effective in treating diabetic macular edema as it improved vision and resulted in fewer complications. PMID:27103811

  9. Risk factors of recurrence of macular oedema associated with branch retinal vein occlusion after intravitreal bevacizumab injection.

    PubMed

    Yoo, Jun Ho; Ahn, Jaemoon; Oh, Jaeryung; Cha, Jaehyung; Kim, Seong-Woo

    2017-02-23

    To identify risk factors of recurrence of macular oedema in branch retinal vein occlusion (BRVO) after intravitreal bevacizumab (IVB) injection. The records of 63 patients who underwent IVB injection for macular oedema secondary to BRVO with at least 6 months of follow-up were reviewed. Patients were evaluated at baseline with fluorescein angiography (FA), optical coherence tomography (OCT) and ultra-wide-field fundus photography (WFP). During follow-up, OCT and WFP were repeated. The area of retinal haemorrhage, central retinal thickness (CRT), area (mm(2)) of capillary non-perfusion within the 1 mm (NPA1), 1-3 mm and 6 mm zones of the ETDRS circle, foveal capillary filling time, degree (°) of foveal capillary network destruction and FA pattern were analysed. Macular oedema recurred in 41 of 63 (65.1%) eyes after initial IVB injection. A binary logistic regression model showed that NPA1 (OR=434.97; 95% CI=5.52 to 34262.12, p=0.006) and initial CRT (OR=1.004; 95% CI=1.000 to 1.008, p=0.015) were significantly associated with the recurrence of macular oedema. Receiver operating characteristic curve analysis identified an NPA1 of 0.36 mm(2) (AUC: 0.735, sensitivity: 70.7%; specificity: 63.6%) and an initial CRT of 570 µm (AUC: 0.745, sensitivity: 63.4%; specificity: 77.3%) as cut-off values for predicting recurrence of macular oedema. Patients with BRVO with non-perfusion of more than half of the 1 mm zone of the ETDRS circle or with an initial CRT >570 µm should be closely monitored for macular oedema recurrence within 6 months of IVB injection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Anterior segment changes following intravitreal bevacizumab injection for treatment of neovascular glaucoma

    PubMed Central

    Canut, MI; Alvarez, A; Nadal, J; Abreu, R; Abreu, JA; Pulido, JS

    2011-01-01

    Background: The purpose of this study was to describe anterior segment changes in a prospective, interventional, noncomparative case series of patients with neovascular glaucoma secondary to proliferative diabetic retinopathy treated with intravitreal bevacizumab. Methods: Five consecutive patients with neovascular glaucoma and a refractory, symptomatic elevation of intraocular pressure and pronounced anterior segment congestion received intravitreal bevacizumab 1.25 mg/0.05 mL. Follow-up examinations were performed at 4–16 weeks by the same specialists, with testing performed at hour 48, week 1, and months 1, 3, and 6 after intravitreal bevacizumab. Results: We observed a significant difference (P = 0.021) between initial and mean neovascularization at three months in all the quadrants. At three months, median intraocular pressure was 19 ± 5.38 (range 12–26) mmHg. In three of the five cases, diode laser cyclophotocoagulation was required, and in one case a trabeculectomy was performed. One patient showed complete synechial angle closure 48 hours after treatment which required cyclodestructive procedures to normalize intraocular pressure. Conclusion: Intravitreal bevacizumab achieves complete regression of neovascularization in neovascular glaucoma secondary to proliferative diabetic retinopathy, and this regression is stable when associated with treatment of the underlying disease and should be investigated more thoroughly as an adjunct in the management of neovascular glaucoma. PMID:21629579

  11. Photoreceptor degeneration by intravitreal injection of N-methyl-N-nitrosourea (MNU) in rabbits: a pilot study.

    PubMed

    Rösch, Sarah; Werner, Claudia; Müller, Frank; Walter, Peter

    2017-02-01

    Pilot study on the attempt to induce selective photoreceptor degeneration in the rabbit eye by intravitreal injection of MNU, facing the difficulties of the evaluation of retinal degeneration by different in-vivo and in-vitro methods in such a large eye animal model. Eight pigmented Chinchilla Bastard rabbits were injected intravitreally with MNU (1 × 1mg/kg body weight (BW), 1 × 2mg/kg BW, 3 × 3mg/kg BW, 1 × 4mg/kg BW, 1 × 6mg/kg BW, and 1 × DMSO + PBS as control). One, 2, and 3 weeks after injection, the effects on the rabbit retina were examined in vivo using clinical observation (macroscopic images, funduscopy, weighing of the animals), measurement of intraocular pressure (IOP), full-field Electroretinography (ffERG), and spectral-domain Optical Coherence Tomography (sd-OCT). After 3 weeks follow-up, blood samples were taken to evaluate the general health status of the animals, and immunohistochemistry (IH) was performed on sections obtained from six different regions throughout the whole retina to evaluate MNU effects in more detail. It was difficult to observe the effects of MNU on retinal structure by OCT in vivo. Only the temporal quadrant of the retina could be visualized. Therefore, it was indispensible to evaluate the effects of MNU on the retina in vitro by examining six areas of the retina using immunohistochemistry. Furthermore, immunohistochemistry plays a decisive role to evaluate the effects on retinal cells other than photoreceptors while in H&E staining, namely the cell count of the ONL can be observed. The results obtained in vivo and in vitro in this study mainly follow the results of a previous study in mice. The low doses of MNU (1, 2 mg/kg BW) had no effects on retinal function and morphology, while high doses (4, 6 mg/kg BW) led to retinal changes in combination with significant side-effects (e.g., cataractous changes). Injection of 3 mg/kg BW MNU induced selective photoreceptor degeneration. However, the degree of

  12. Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections.

    PubMed

    Xu, Xu; Xu, Zhaokang; Liu, Junyi; Zhang, Zhaoliang; Chen, Hao; Li, Xingyi; Shi, Shuai

    To visually trace the diffusion and biodistribution of amphiphilic cation micelles after vitreous injection, various triblock copolymers of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone)-polyethylenimine were synthesized with different structures of hydrophilic and hydrophobic segments, followed by labeling with near-infrared fluorescent dye Cyanine5 or Cyanine7. The micellar size, polydispersity index, and surface charge were measured by dynamic light scattering. The diffusion was monitored using photoacoustic imaging in real time after intravitreal injections. Moreover, the labeled nanoparticle distribution in the posterior segment of the eye was imaged histologically by confocal microscopy. The results showed that the hydrophilic segment increased vitreous diffusion, while a positive charge on the particle surface hindered diffusion. In addition, the particles diffused through the retinal layers and were enriched in the retinal pigment epithelial layer. This work tried to study the diffusion rate via a simple method by using visible images, and then provided basic data for the development of intraocular drug carriers.

  13. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study.

    PubMed

    Brown, David M; Heier, Jeffrey S; Clark, W Lloyd; Boyer, David S; Vitti, Robert; Berliner, Alyson J; Zeitz, Oliver; Sandbrink, Rupert; Zhu, Xiaoping; Haller, Julia A

    2013-03-01

    To evaluate intravitreal aflibercept injections (IAI; also called VEGF Trap-Eye) for patients with macular edema secondary to central retinal vein occlusion (CRVO). Randomized controlled trial. This multicenter study randomized 189 patients (1 eye/patient) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept (IAI 2Q4) (n = 115) or sham (n = 74). From week 24 to week 52, all patients received 2 mg intravitreal aflibercept as needed (IAI 2Q4 + PRN and sham + IAI PRN) according to retreatment criteria. The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24. Additional endpoints included visual, anatomic, and quality-of-life NEI VFQ-25 outcomes at weeks 24 and 52. At week 24, 56.1% of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3% of sham patients (P < .001). At week 52, 55.3% of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1% of sham + IAI PRN patients (P < .001). At week 52, IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN (P < .001). The most common adverse events for both groups were conjunctival hemorrhage, eye pain, reduced visual acuity, and increased intraocular pressure. Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in a statistically significant improvement in visual acuity at week 24, which was largely maintained through week 52 with intravitreal aflibercept PRN dosing. Intravitreal aflibercept injection was generally well tolerated. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Contribution of saccadic motion to intravitreal drug transport: theoretical analysis.

    PubMed

    Balachandran, Ram K; Barocas, Victor H

    2011-05-01

    The vitreous humor liquefies with age and readily sloshes during eye motion. The objective was to develop a computational model to determine the effect of sloshing on intravitreal drug transport for transscleral and intra-vitreal drug sources at various locations A finite element model based on a telescopic implicit envelope tracking scheme was developed to model drug dispersion. Flow velocities due to saccadic oscillations were solved for and were used to simulate drug dispersion. Saccades induced a three-dimensional flow field that indicates intense drug dispersion in the vitreous. Model results showed that the time scale for transport decreased for the sloshing vitreous when compared to static vitreous. Macular concentrations for the sloshing vitreous were found be much higher than that for the static vitreous. For low viscosities the position of the intravitreal source did not have a big impact on drug distribution. Model results show that care should be taken when extrapolating animal data, which are mostly done on intact vitreous, to old patients whose vitreous might be a liquid. The decrease in drug transport time scales and changes in localized concentrations should be considered when deciding on treatment modalities and dosing strategies.

  15. Contribution of Saccadic Motion to Intravitreal Drug Transport: Theoretical Analysis

    PubMed Central

    Balachandran, Ram K.

    2011-01-01

    Purpose The vitreous humor liquefies with age and readily sloshes during eye motion. The objective was to develop a computational model to determine the effect of sloshing on intravitreal drug transport for transscleral and intra-vitreal drug sources at various locations Methods A finite element model based on a telescopic implicit envelope tracking scheme was developed to model drug dispersion. Flow velocities due to saccadic oscillations were solved for and were used to simulate drug dispersion. Results Saccades induced a three-dimensional flow field that indicates intense drug dispersion in the vitreous. Model results showed that the time scale for transport decreased for the sloshing vitreous when compared to static vitreous. Macular concentrations for the sloshing vitreous were found be much higher than that for the static vitreous. For low viscosities the position of the intravitreal source did not have a big impact on drug distribution. Conclusion Model results show that care should be taken when extrapolating animal data, which are mostly done on intact vitreous, to old patients whose vitreous might be a liquid. The decrease in drug transport time scales and changes in localized concentrations should be considered when deciding on treatment modalities and dosing strategies. PMID:21258958

  16. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

    PubMed

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-11-13

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

  17. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

    PubMed Central

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

  18. Efficacy of Topical Ofloxacin 0.3 % Administration on Conjunctival Bacterial Flora in Diabetic Patients Undergoing Intravitreal Injections.

    PubMed

    Plotas, Panagiotis; Makri, Olga E; Georgalas, Ilias; Pharmakakis, Nikolaos; Vantarakis, Apostolos; Georgakopoulos, Constantine D

    2016-08-03

    This prospective, randomized case series study aims to evaluate the efficacy of ofloxacin 0.3% eye drops in eradication of conjunctival bacterial flora in diabetic patients undergoing intravitreal injections (IVI). Ninety-two diabetic patients (92 eyes) scheduled to undergo intravitreal injection of ranibizumab due to diabetic macular edema were enrolled in the study. Patients were randomly assigned to three different groups. Group 1 (n=32) received ofloxacin eye drops the day before before IVI (four times); patients in Group 2 (n=29) were administered ofloxacin one hour before IVI (every 15 minutes), while Group 3 (n=31) comprised patients that received combined administration of ofloxacin both one day and one hour before IVI (eight doses). Samples were collected from the injection site before and after antibiotic administration. Culture results from BACTEC broth and positive cultures in blood agar and Sabouraud's dextrose agar plates were measured. In Group 1, BACTEC broth positive cultures decreased from 84.4% at baseline to 50% after ofloxacin administration (p=0.007), and blood agar positive cultures reduced from 65.63% to 34.38% (p=0.02). In Group 2, positive cultures significantly decreased in BACTEC broth (from 79.3% at baseline to 48.28%; p=0.027) and in blood agar (from 68.97% to 37.13%; p=0.034). In Group 3, positive cultures decreased from 77.42% at baseline to 32.26% (p=0.0008) and from 58.06% at baseline to 22.58% (p=0.009) in BACTEC broth and blood agar, respectively. No microorganisms were isolated from Sabouraud's dextrose agar plates. The combined one day/one hour (eight doses) ofloxacin administration in diabetic patients is extremely effective in reducing conjunctival bacterial flora. The application of topical ofloxacin for one day or one hour before IVI is also significantly effective.

  19. Endophthalmitis following intravitreal injection of anti-VEGF agents: long-term outcomes and the identification of unusual micro-organisms.

    PubMed

    Sachdeva, Mira M; Moshiri, Ala; Leder, Henry A; Scott, Adrienne W

    2016-12-01

    While the development of targeted molecular therapy to inhibit vascular endothelial growth factor (VEGF) has revolutionized the treatment and visual prognosis of highly prevalent retinal diseases such as diabetic retinopathy and age-related macular degeneration, each intravitreal injection of these agents carries a small risk of endophthalmitis which can be visually devastating. In the absence of specific guidelines, current management of post-injection endophthalmitis is typically extrapolated from data regarding endophthalmitis occurring after cataract surgery despite potential differences in pathogenic organisms and clinical course. Here, we assess the contribution of intravitreal injections of anti-VEGF agents to all cases of endophthalmitis at our tertiary care referral center and characterize the clinical outcomes and microbial pathogens associated with post-injection endophthalmitis in order to inform management of this serious iatrogenic condition. During the 7-year study period analyzed, 199 cases of endophthalmitis were identified using billing records. Of these, the most common etiology was post-surgical, accounting for 62 cases (31.2 %), with bleb-associated, endogenous, and corneal ulcer-related infections representing the next most frequent causes, comprising 15.6 % (31/199), 13.1 % (26/199), and 13.6 % (27/199) of all cases, respectively. Intravitreal injections of anti-VEGF agents represented 8.5 % of endophthalmitis (17/199 cases). Intraocular cultures yielded positive results in 75 % of post-injection cases, with the majority associated with coagulase-negative Staphylococcus. Consistent with prior literature, a case of Strep viridans displayed more rapid onset and progression. We also report the first association of Enterobacter cloacae and Lactococcus garvieae with post-injection endophthalmitis. While all but one patient were treated with initial vitreous tap and intravitreal injection of antibiotics, both patients with these rare

  20. Vitrectomy Before Intravitreal Injection of AAV2/2 Vector Promotes Efficient Transduction of Retinal Ganglion Cells in Dogs and Nonhuman Primates.

    PubMed

    Tshilenge, Kizito-Tshitoko; Ameline, Baptiste; Weber, Michel; Mendes-Madeira, Alexandra; Nedellec, Steven; Biget, Marine; Provost, Nathalie; Libeau, Lyse; Blouin, Véronique; Deschamps, Jack-Yves; Le Meur, Guylène; Colle, Marie-Anne; Moullier, Philippe; Pichard, Virginie; Rolling, Fabienne

    2016-06-01

    Recombinant adeno-associated virus (AAV) has emerged as a promising vector for retinal gene delivery to restore visual function in certain forms of inherited retinal dystrophies. Several studies in rodent models have shown that intravitreal injection of the AAV2/2 vector is the optimal route for efficient retinal ganglion cell (RGC) transduction. However, translation of these findings to larger species, including humans, is complicated by anatomical differences in the eye, a key difference being the comparatively smaller volume of the vitreous chamber in rodents. Here, we address the role of the vitreous body as a potential barrier to AAV2/2 diffusion and transduction in the RGCs of dogs and macaques, two of the most relevant preclinical models. We intravitreally administered the AAV2/2 vector carrying the CMV-eGFP reporter cassette in dog and macaque eyes, either directly into the vitreous chamber or after complete vitrectomy, a surgical procedure that removes the vitreous body. Our findings suggest that the vitreous body appears to trap the injected vector, thus impairing the diffusion and transduction of AAV2/2 to inner retinal neurons. We show that vitrectomy before intravitreal vector injection is an effective means of overcoming this physical barrier, improving the transduction of RGCs in dog and macaque retinas. These findings support the use of vitrectomy in clinical trials of intravitreal gene transfer techniques targeting inner retinal neurons.

  1. Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury

    PubMed Central

    Adornetto, Annagrazia; Cavaliere, Federica; Varano, Giuseppe Pasquale; Rusciano, Dario; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

    2015-01-01

    Purpose Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is an activator of adenylate cyclase that decreases IOP by reducing aqueous humor production and functions as a neuroprotector due to its neurotrophin-stimulating activity. Homotaurine is a natural aminosulfonate compound endowed with neuromodulatory effects, while the dipeptide L-carnosine is known for its antioxidant properties. Methods Retinal ischemia was induced in the right eye of adult male Wistar rats by acutely increasing the IOP. Forskolin, homotaurine, and L-carnosine were intravitreally injected and RGC survival evaluated following retrograde labeling with FluoroGold. Total and phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β) protein levels, as well as calpain activity, were analyzed with western blot. Protein kinase A (PKA) was inhibited by intravitreal injection of H89. Results A synergic neuroprotective effect on RGC survival was observed following the combined treatment with forskolin, homotaurine, and L-carnosine compared to forskolin alone. The observed neuroprotection was associated with reduced calpain activity, upregulation of phosphoinositide 3-kinase (PI3K)/Akt pathway, and inhibition of GSK-3β but was independent from PKA activation and distinct from the hypotensive effects of forskolin. Conclusions A multidrug/multitarget approach, by interfering with several pathways involved in RGC degeneration, may be promising to achieve glaucoma neuroprotection. PMID:26167113

  2. ULTRASONOGRAPHIC FINDINGS IN THE VITREOUS OF PATIENTS WITH AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS.

    PubMed

    Mato-Gondelle, Tamara; Bande, Manuel F; Paniagua, Laura; Rodríguez-Cid, María J; Abraldes, Maximino; Fernández, Maribel; Blanco-Teijeiro, María J; Piñeiro, Antonio

    2017-08-16

    We aimed to assess the relationship of repeated intravitreal injection of anti-vascular endothelial growth factor, the main treatment for exudative age-related macular degeneration, with changes in vitreous ultrasonographic findings in patients with age-related macular degeneration. We retrospectively collected data from 41 patients (41 age-related macular degeneration eyes, 41 control eyes) on age, sex, number of injections, and type of anti-vascular endothelial growth factor (ranibizumab, aflibercept). Ocular ultrasonography was performed with open eyelids, under topical anesthesia, and using carbomers as ultrasonographic gel. Topographic, quantitative, and kinetic ultrasonography was performed in all eye quadrants using a 10-MHz posterior pole probe, and vitreous reflectivity was assessed. The mean age of patients was 79 (range: 59-94) years, with a mean of five intravitreal anti-vascular endothelial growth factor injections (range: 1-13). No significant ultrasonographic differences were found relative to the incidence of partial or complete posterior vitreous detachment. Vitreous hyperechogenicity increased in the treated eye (P < 0.001), and the vitreous reflectivity range increased with the number of injections (P = 0.041, R = 0.214). However, the type of anti-vascular endothelial growth factor used and the time elapsed since the last intravitreal injection was not significant (P > 0.05). These preliminary results indicate a proportional increase in ultrasonographic reflectivity of vitreous gel with the number of injections.

  3. Safety study of 38,503 intravitreal ranibizumab injections performed mainly by physicians in training and nurses in a hospital setting.

    PubMed

    Hasler, Pascal W; Bloch, Sara Brandi; Villumsen, Jørgen; Fuchs, Josefine; Lund-Andersen, Henrik; Larsen, Michael

    2015-03-01

    To evaluate and to compare the safety of intravitreal ranibizumab injections performed by physicians and nurses at a single large hospital clinic in Denmark during 5 years. Retrospective, interventional, non-comparative study. All eyes that underwent a protocolized ranibizumab injection procedure performed in an operating room mainly by nurses and physicians in their first year of ophthalmology training. A total of 4623 eyes in 3679 patients with subretinal neovascularization secondary to a variety of retinal diseases, mainly neovascular AMD treated with intravitreal therapy (IVT) at the Glostrup Hospital from January 1, 2007 to December 31, 2011 with a mean follow-up of 12.2 months (95% confidence interval: 11.9-12.6). Frequency of endophthalmitis, traumatic cataract, intraocular haemorrhage and retinal detachment from 2007 to 2012. Overall, 38,503 intravitreal ranibizumab injections were performed in 4623 eyes. Injections were performed by nurses (32.5%), ophthalmology residents (61.3%) and vitreoretinal surgeons (6.2%). Severe complications to treatment were observed in 17 eyes: Endophthalmitis (14 eyes, 0.36 ‰ of injections whereof seven cases were culture-positive), anterior uveitis (one eye, 0.026 ‰), traumatic cataract (one eye, 0.026 ‰) and rhegmatogenous retinal detachment (one eye, 0.026 ‰). Retinal pigment epithelial tears were registered in 14 eyes in 14 subjects within the first year of treatment with ranibizumab. Of the 14 cases of endophthalmitis, seven occurred within a period of 5 weeks in 2010 when occasionally abnormal needle outflow resistance prompted the needle replacement in the operating room. No drug-related adverse events were recorded. Intravitreal ranibizumab injection performed by nurses and physicians without preinjection topical antibiotics was associated with a rate of injection-related adverse events of 0.44 ‰. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  4. Biochemical changes induced by intravitreally-injected doxorubicin in the iris-ciliary body and lens of the rabbit eye.

    PubMed

    Phylactos, A C; Unger, W G

    1998-01-01

    The aim of this study was to examine the chronic effects and mode of action of doxorubicin in ocular tissues. A dose of 10 microg (17.24 nanomoles) of doxorubicin hydrochloride in 20 microl sterile saline were intravitreally injected, under local anaesthesia, in one eye of 13 rabbits and 50 microg (86.20 nanomoles) were similarly injected in one eye of 3 rabbits. The contralateral eye received 20 microl of saline only. The dose of 50 microg induced initially mild uveal inflammation which became chronic and turned into circular iritis. Both doses of the drug induced cataract of the lens and clouding of the cornea within 2-3 months. The activity of superoxide dismutase, in iris-ciliary bodies and lenses treated with either 10 or 50 microg of the compound, was significantly lower relative to that in respective control tissues. In contrast to superoxide dismutase, catalase showed an increased activity in experimental tissues relative to control. The lysosomal hydrolases acid phosphatase, N-acetyl-B-D-glucosaminidase, aryl sulphatase and acid cathepsin, all showed significantly elevated activities in iris-ciliary body tissues one year after injection with the 50 microg doxorubicin. The reduction in superoxide dismutase activity may render ocular tissues susceptible to peroxidative attack and the increased activities of lysosomal hydrolases may contribute to chronic cell injury and inflammation.

  5. Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Rodent Model of Anterior Ischemic Optic Neuropathy

    PubMed Central

    Touitou, Valerie; Johnson, Mary A.; Guo, Yan; Miller, Neil R.; Bernstein, Steven L.

    2013-01-01

    Purpose. Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve–related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both. Methods. Toxicity was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. Efficacy was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed. Results. Toxicity: IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers. Efficacy: IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION. Conclusions. A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction. PMID:24106118

  6. Incidence, Risk Factors, and Timing of Elevated Intraocular Pressure After Intravitreal Triamcinolone Acetonide Injection for Macular Edema Secondary to Retinal Vein Occlusion: SCORE Study Report 15.

    PubMed

    Aref, Ahmad A; Scott, Ingrid U; Oden, Neal L; Ip, Michael S; Blodi, Barbara A; VanVeldhuisen, Paul C

    2015-09-01

    The Standard of Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study showed that intravitreal triamcinolone acetonide (IVTA) is effective at reducing macular edema and improving visual acuity in participants with retinal vein occlusion. Secondary analysis of the incidence, risk factors, and timing of intraocular pressure (IOP) elevation occurring after IVTA provides guidance for clinical decision making and management of patients treated with IVTA. To investigate the incidence, risk factors, and time course of IOP elevation in participants in the SCORE Study. Secondary analysis conducted from August through December 2014 of a prospective, randomized clinical trial featuring an evaluable population conducted at 75 clinical sites. Six hundred eighty-two patients with macular edema secondary to retinal vein occlusion were enrolled in the study. The SCORE Study enrollment period ran from November 4, 2004, to February 29, 2008, with participant follow-up ending February 28, 2009. Study participants were randomized to standard of care, 1 mg of IVTA, or 4 mg of IVTA therapy and followed up for a mean (SD) of 24.7 (10.3) months. Intraocular pressure elevation greater than 10 mm Hg from baseline. Kaplan-Meier incidences of IOP elevation greater than 10 mm Hg from baseline at 36 months were 0.02 (95% CI, 0.01-0.06), 0.09 (95% CI, 0.05-0.14), and 0.45 (95% CI, 0.38-0.53) in the standard of care, 1-mg IVTA, and 4-mg IVTA groups, respectively. The rates of IOP-related events were higher for the 4-mg IVTA group compared with the other groups (P ≤ .001 for main outcome measure). Younger age, 4-mg IVTA vs 1-mg IVTA treatment, and higher baseline IOP were found to confer greater risk for IOP-related events (P < .05 for all). The median number of days from time of first injection to IOP elevation greater than 10 mm Hg from baseline was 34.0 and 52.5 days in participants treated with 1-mg and 4-mg IVTA, respectively. Intravitreal triamcinolone acetonide injection

  7. Effective Intravitreal Injections of Bevacizumab in a Case of Serous Macular Detachment from the Superior Border of the Posterior Staphyloma

    PubMed Central

    Tsubota, Yukiko; Takahashi, Hidenori; Sugisaki, Kenji; Tanabe, Tatsuro; Fujino, Yujiro

    2017-01-01

    Purpose We present an atypical case of submacular fluid leading to serous macular detachment. Method/Patient A 69-year-old man was evaluated for metamorphopsia in the left eye. Results Best-corrected visual acuity was 20/25 in both eyes. He had undergone cataract surgeries in both eyes 12 years ago. The axial length was 25.93 mm (OD) and 24.12 mm (OS). Optical coherence tomography showed posterior staphylomas and subretinal fluid on the superior border of the staphylomas in both eyes; in the left eye, submacular fluid was noted extending up to the macula. Fundus fluorescein angiography revealed leakage from the superior border of the staphylomas in both eyes. The fluid persisted for 4 months. Four consecutive, monthly injections of bevacizumab (1.25 mg/0.05 mL) were administered in the left eye; subsequently, the subretinal fluid gradually dissipated from the macula and became localized at the superior border of the staphyloma. This localization persisted for 12 months. Conclusions We have detailed a case of submacular fluid that spread from the superior border of the posterior staphyloma in a patient with macular detachment, in whom intravitreal injections of bevacizumab were highly effective in eliminating the fluid. PMID:28203196

  8. Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections

    PubMed Central

    Xu, Xu; Xu, Zhaokang; Liu, Junyi; Zhang, Zhaoliang; Chen, Hao; Li, Xingyi; Shi, Shuai

    2016-01-01

    To visually trace the diffusion and biodistribution of amphiphilic cation micelles after vitreous injection, various triblock copolymers of monomethoxy poly(ethylene glycol)–poly(ε-caprolactone)–polyethylenimine were synthesized with different structures of hydrophilic and hydrophobic segments, followed by labeling with near-infrared fluorescent dye Cyanine5 or Cyanine7. The micellar size, polydispersity index, and surface charge were measured by dynamic light scattering. The diffusion was monitored using photoacoustic imaging in real time after intravitreal injections. Moreover, the labeled nanoparticle distribution in the posterior segment of the eye was imaged histologically by confocal microscopy. The results showed that the hydrophilic segment increased vitreous diffusion, while a positive charge on the particle surface hindered diffusion. In addition, the particles diffused through the retinal layers and were enriched in the retinal pigment epithelial layer. This work tried to study the diffusion rate via a simple method by using visible images, and then provided basic data for the development of intraocular drug carriers. PMID:27785015

  9. Fellow eye effect of unilateral intravitreal bevacizumab injection in eyes with diabetic macular edema.

    PubMed

    Hanhart, J; Tiosano, L; Averbukh, E; Banin, E; Hemo, I; Chowers, I

    2014-06-01

    Anti-vascular endothelial growth factor compounds are routinely used for the treatment of diabetic macular edema (DME). We aim to evaluate for the existence and magnitude of treatment effect on fellow un-injected eyes. A consecutive group of patients with bilateral DME who received unilateral bevacizumab injections was retrospectively evaluated. Data collected included demographics, ophthalmic and systemic findings, and optical coherence tomography (OCT) measurements of macular thickness. Thirty-five patients were evaluated. Mean follow-up was 245 days (range: 30-800), and the mean number of bevacizumab injections was 3.6 (range: 1-11). At end of follow-up, the mean (SD) OCT central subfield thickness reduced by 72 ± 112 micron in the injected eye (from 469 ± 139 to 397 ± 120 micron; P=0.001), while in the non-injected eye it reduced by 49 ± 75 micron (from 380 ± 130 to 331 ± 106 micron; P<0.001). Sixteen injected eyes (45.7%) showed central subfield thickness reduction of ≥50 micron while 10 (28.6%) non-injected eyes showed such thickness reduction. Improved VA following treatment was detected in 14 (40%) injected eyes and in 15 (43%) non-injected eyes. Unilateral bevacizumab injections in patients with bilateral DME are often associated with bilateral response. Anti-vascular endothelial growth factor compounds are routinely used for the treatment of diabetic macular edema (DME). In this retrospective study, we show that unilateral bevacizumab injections often result in reduction of the macular thickness in the fellow un-injected eye.

  10. Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR.

    PubMed

    Yin, Philip D; Kurup, Shree K; Fischer, Steven H; Rhee, Henry H; Byrnes, Gordon A; Levy-Clarke, Grace A; Buggage, Ronald R; Nussenblatt, Robert B; Mican, JoAnn M; Wright, Mary E

    2007-03-01

    Progressive outer retinal necrosis (PORN) is an ocular disease in individuals with AIDS and is associated with substantial morbidity. The optimal management of PORN and its clinical course in the HAART era is unclear. We report a case of successfully managed PORN that provides insight into the monitoring and treatment of this disease. Intravitreal injections and intravenous therapy targeted towards varicella zoster virus (VZV) were used to treat PORN. HAART was initiated for HIV-1 therapy. Serial PCR for VZV was performed on aqueous humor to monitor the clinical course. The presence of VZV DNA from aqueous humor correlated with clinical exacerbations of disease. Initiation of twice weekly intravitreal injections with dual antiviral drugs appeared to be an important therapeutic intervention that resulted in remission of PORN. Secondary prophylaxis against VZV was successfully withdrawn after HAART induced partial immune recovery. In addition to aggressive therapy with intravitreal injections, HAART and quantitative measurements of VZV DNA from aqueous humor have important roles in the management of PORN. A multidisciplinary approach involving specialists in infectious diseases, ophthalmology, and clinical microbiology will improve the chances for successful long-term outcomes.

  11. The combination of phacoemulsification surgery and intravitreal triamcinolone injection in patients with cataract and diabetic macular edema

    PubMed Central

    Ozgur, Ozlen Rodop; Ozkurt, Yelda; Kulekci, Zeynep; Evciman, Tufan

    2015-01-01

    Purpose To assess the safety and efficiency of combined phacoemulsification (PHACO) surgery and intravitreal triamcinolone (IVTA) injection with or without macular grid laser photocoagulation in patients with cataract and diabetic macular edema. Material and methods This prospective study included 41 eyes of 36 diabetic patients with cataract and coexisting clinically significant macular edema (CSME). After PHACO and IVTA injection eyes were divided into two groups: the laser and IVTA group (Group 1) and only IVTA group (Group 2). Preoperative and postoperative best corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were recorded. Paired sample t-test was used to compare data in the groups and C square test for qualitative variables. Results Postoperative BCVA was significantly higher than the initial BCVA during the follow-up period in both groups (p < 0.01). The BCVA 6 months after surgery was significantly higher in group 1 than in group 2 (p < 0.01). There was no statistically significant difference in IOP between two groups preoperatively and postoperatively during the follow-up period (p > 0.05). There was no statistically significant difference between both groups in mean CMT preoperatively and 2nd week, 2nd month and 3rd month after surgery (p > 0.05). The mean CMT 6 months after surgery was statistically significantly lower in group 1 than in group 2 (p < 0.01). Conclusions PHACO surgery combined with IVTA injection improves BCVA and provides a decrease in CMT in diabetic patients with CSME. Additional macular grid laser photocoagulation after surgery helps to preserve this improvement in BCVA and decrease in CMT. PMID:26949356

  12. COMPARISON OF INTRAVITREAL INJECTION OF RANIBIZUMAB VERSUS LASER THERAPY FOR ZONE II TREATMENT-REQUIRING RETINOPATHY OF PREMATURITY.

    PubMed

    Zhang, Guoming; Yang, Mingmin; Zeng, Jian; Vakros, Georgios; Su, Kangjin; Chen, Miaohong; Li, Huilin; Tian, Ruyin; Li, Na; Tang, Song; He, Honghui; Tan, Wenjing; Song, Xiangmei; Zhuang, Runsen

    2017-04-01

    To compare the efficacy of intravitreal injection of ranibizumab (IVR) monotherapy and laser therapy for treatment-requiring retinopathy of prematurity (ROP) in Zone II. A prospective, randomized, controlled single-center trial was applied from January 2014 to December 2014; infants who were diagnosed as Zone II treatment-requiring ROP (i.e., Zone II Stage 2 or 3 ROP with plus disease) were randomly assigned to receive IVR monotherapy or laser therapy, and the follow-up interval was at least 6 months. Any eyes that developed recurrence of ROP underwent crossover re-treatment. A total of 100 eyes of 50 ethnic Han Chinese infants were enrolled. At the last follow-up, 26 eyes of 13 infants developed recurrence of ROP in the IVR group and 2 eyes of 1 infant developed recurrence of ROP in the laser therapy group. There was a significant statistical difference in the rate of ROP recurrence between IVR and laser therapy to treat Zone II treatment-requiring ROP (P = 0.001). Although IVR appears to regress ROP to certain levels and continue to promote the vascularization of peripheral retinal vessels, a substantial proportion of infants developed recurrence of ROP after a single-dose IVR. Therefore, IVR is not recommended as a single-dose monotherapy for Zone II treatment-requiring ROP.

  13. Combination of Intravitreal Injection of Ranibizumab and Photocoagulation for the Treatment of Aggressive Posterior Retinopathy of Prematurity with Vitreous Hemorrhage

    PubMed Central

    Huang, Qiujing; Lv, Jiao

    2016-01-01

    To investigate the efficacy of intravitreal ranibizumab (IVR) combined with laser photocoagulation for aggressive posterior retinopathy of prematurity (AP-ROP) patients with vitreous hemorrhage, we conducted a retrospective observational case series study. A total of 37 eyes of 20 patients' medical records were reviewed. Patients first received IVR (0.25 mg/0.025 mL) and later photocoagulation. The mean postconceptual age of injection was 34.6 ± 1.4 weeks, and the mean follow-up period was 39.3 ± 8.3 weeks. During the follow-up, 96.6% eyes had various degree of rapid absorption of vitreous hemorrhage after IVR. The mean time of received first photocoagulation after IVR was 4.8 ± 2.9 weeks. Ten (27.0%) eyes received second laser therapy and the mean time of second laser therapy after IVR was 3.2 ± 0.8 weeks. All eyes exhibited adequate regression of ROP and were stable with attached retina. Fibrosis membrane was observed in seven eyes (18.9%) and three of them demonstrated mild ectopic macula. No significant side effects related to IVR were observed. So IVR could be conducted as primary treatment of AP-ROP associated with vitreous hemorrhage, which can improve the fundus visibility, followed by conventional photocoagulation. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with conventional interventions. PMID:28070414

  14. EVALUATION OF SHORT-TERM OUTCOMES OF INTRAVITREAL AFLIBERCEPT INJECTIONS FOR AGE-RELATED MACULAR DEGENERATION USING FOCAL MACULAR ELECTRORETINOGRAPHY.

    PubMed

    Takayama, Kei; Kaneko, Hiroki; Ueno, Shinji; Maruko, Ruka; Piao, Chang-Hua; Yasuda, Shunsuke; Kawano, Kenichi; Ito, Yasuki; Terasaki, Hiroko

    2017-03-01

    To evaluate the relationship between morphological changes and functional improvements assessed using focal macular electroretinograms after intravitreal aflibercept (IVA) injections in eyes with wet age-related macular degeneration. The clinical records of 42 eyes of 42 consecutive patients with naive, wet age-related macular degeneration received 3 monthly IVA were reviewed. The best-corrected visual acuity, central foveal thickness, outer retinal thickness, inner retinal thickness at baseline and 1 month after each IVA, and focal macular electroretinograms at baseline and 1 month after the first and third IVA were compared. Best-corrected visual acuity was improved after the third IVA (P = 0.0091). Central foveal thickness and outer retinal thickness showed decreases after every IVA (P < 0.001, respectively). Inner retinal thickness showed a decrease after the second IVA (P = 0.002), after and third IVA (P = 0.001). On focal macular electroretinograms, a- and b-wave amplitudes showed increases after the third IVA (P = 0.0028, P = 0.0012, respectively). Significant correlations were observed between best-corrected visual acuity and central foveal thickness, a-wave amplitude and outer retinal thickness, and b-wave amplitude and inner retinal thickness changes after the third IVA. All parameters significantly recovered after three monthly IVA, with a correlation between functional improvements and morphological changes.

  15. Aqueous vascular endothelial growth factor and clinical outcomes correlation after single intravitreal injection of bevacizumab in patients with neovascular age-related macular degeneration.

    PubMed

    Cabral, Thiago; Lima, Luiz H; Polido, Júlia; Duong, Jimmy; Okuda, Érika; Oshima, Akiyoshi; Serracarbassa, Pedro; Regatieri, Caio V; Belfort, Rubens

    2017-01-01

    To evaluate the concentration of vascular endothelial growth factor (VEGF) in aqueous humor after a single intravitreal injection of bevacizumab (IVB) in eyes with neovascular age-related macular degeneration (AMD). In this prospective interventional case series study, 24 eyes of 24 patients with types 1 and 2 choroidal neovascularization secondary to neovascular AMD were treated with a single intravitreal injection of bevacizumab. Aqueous humor samples were obtained before the intravitreal injection and at one week, one month, and three months follow-up periods. Best-corrected visual acuity (BCVA) and three spectral-domain optical coherence tomography parameters (central retinal thickness, macular volume and macular area) were also analyzed and correlated with VEGF expression at the baseline and each follow-up period. All of the ninety-six aqueous humor study taps were well tolerated by the study patients without adverse events. Increased VEGF levels (mean ± SD = 179.7 ± 88.3 pg/mL) were observed in the aqueous humor of all study patients before the intravitreal injection of bevacizumab. At all follow-up periods, compared to baseline, levels of VEGF significantly reduced (P < 0.0001), and BCVA significantly improved (P < 0.005). The lowest VEGF expression was observed at 1 week, and the greatest BCVA improvement occurred 1 month after treatment. At 1 month, central retinal thickness (CRT), macular volume (MV), and macular area (MA) significantly reduced compared to baseline (P < 0.0001, P = 0.0005, P = 0.007, P = 0.009, respectively). At 1 week and 3 months, although without statistical significance (P > 0.005), CRT, MV and MA also reduced in comparison to baseline. Single intravitreal bevacizumab injection in eyes with neovascular AMD resulted in a substantial decrease of aqueous VEGF levels 1 week after treatment with the greatest improvement of clinical outcomes occurring at 1 month follow-up.

  16. Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate

    PubMed Central

    Pai, Sivakami A; Hebri, Sudhira P; Lootah, Afra M

    2012-01-01

    The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM. PMID:23202396

  17. [Intravitreous injection of bevacizumab and C3F8 gas for the treatment of submacular hemorrhage due to age-related macular degeneration: case reports].

    PubMed

    Ferraz, Daniel Araújo; Bressanim, Gláucio Luciano; Morita, Celso; Takahashi, Walter Yukihiko

    2010-01-01

    The purpose of this case series is to describe if the intravitreal use of bevacizumab and perfluoropropane gas (C3F8) would be beneficial to the displacement of subretinal hemorrhage in patients with age-related macular degeneration (AMD). A retrospective study of 5 eyes that received concurrent intravitreal injection of bevacizumab and C3F8 was performed. The results were graded according to blood displacement under the fovea, best final visual acuity and intraoperative complications. At the initial presentation, mean age of patients was 72.6 +/- 8.9 years-old and duration of symptoms was 13 +/- 9.7 days. From the 5 patients, 3 (60%) were male and 2 (40%) female. The success of submacular hemorrhage full displacement was achieved in 4 patients. The mean preoperative visual acuity (VA) was 1.12 +/- 0.34 logMAR and the mean postoperative VA was 0.92 +/- 0.4 logMAR. No cases of retinal detachment, endophthalmitis, vitreous hemorrhage, uveitis, cataracts and increased intraocular pressure were noted during the follow-up period. Intravitreal bevacizumab and C3F8 injection, associated to prone position can be a valuable therapeutic option for eyes with neovascular age-related macular degeneration and subretinal hemorrhage to the blood displacement out of the foveal area.

  18. ISIS-DME: a prospective, randomized, dose-escalation intravitreal steroid injection study for refractory diabetic macular edema.

    PubMed

    Kim, Judy E; Pollack, John S; Miller, David G; Mittra, Robert A; Spaide, Richard F

    2008-05-01

    : To determine safety and efficacy of intravitreal triamcinolone acetonide (IVTA) for refractory clinically significant diabetic macular edema (DME). : Prospective, randomized, dose-escalation pilot study comparing single injection of 2 mg versus 4 mg doses of IVTA. : Inclusion criteria included clinically significant DME persisting >/=3 months after maximal laser treatment and visual acuity injection. : Mean change in visual acuity at 3 months compared to baseline was 7.1 letters (P = 0.01) in the 2 mg group and 12.5 letters in the 4 mg group (P < 0.0001). However, there was not a significant difference in visual improvement between the 2 mg and 4 mg dose groups (P = 0.11). Vision improved >15 letters at 3 months in 23% (3/13) of 2 mg group and in 33% (5/15) of 4 mg group (P = 0.69), and 0% (0/11) and 21% (3/14) at 6 months, respectively (P = 0.23). Visual improvement was more likely in cystoid-type DME than diffuse DME. Intraocular pressure rise of >/=10 mmHg occurred in 19% (3/16) of 2 mg group and 41% (7/17) of 4 mg group. : Both doses of IVTA were well tolerated and had significant positive effects on refractory DME for short term. There were consistent trends throughout the study that suggest that a 4 mg IVTA may be more effective than a 2 mg dose. The benefit of IVTA was greater for cystoid-type DME.

  19. Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration.

    PubMed

    Sawada, Tomoko; Wang, Xiying; Sawada, Osamu; Saishin, Yoshitsugu; Ohji, Masahito

    2017-06-16

    Clinical evidence supports the efficacy of bimonthly aflibercept injection for age-related macular degeneration. The study aimed to evaluate aqueous vascular endothelial growth factor and aflibercept concentrations and the efficacy of bimonthly aflibercept in patients with age-related macular degeneration. This study is a prospective, interventional case series. Enrolled were 35 eyes with exudative age-related macular degeneration from 35 patients. Patients received three bimonthly intravitreal aflibercept without loading doses. We collected the aqueous humor just before each injection, measured vascular endothelial growth factor and aflibercept concentrations by enzyme-linked immunosorbent assay and measured best-corrected visual acuity and central retinal subfield thickness before and after the injections. Aqueous vascular endothelial growth factor and aflibercept concentrations were measured. The vascular endothelial growth factor concentration was 135.4 ± 60.5 pg/mL (mean ± standard deviation, range 60.6-323.4) at baseline and below the lowest detectable limit in all eyes at month 2 and in 32 eyes at month 4 (P < 0.001 [month 2] and P < 0.001 [month 4]). The mean aflibercept concentration was 20.3 ng/mL at month 2 and 28.0 ng/mL at month 4. The mean logarithm of the minimum angle of resolution visual acuity improved from 0.50 ± 0.36 at baseline to 0.36 ± 0.40 at month 6 (P < 0.001). The mean central retinal subfield thickness decreased from 353 ± 100 μm at baseline to 236 ± 45 μm at month 6 (P < 0.001). Bimonthly aflibercept injections without loading doses may be considered a treatment option for age-related macular degeneration. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  20. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study.

    PubMed

    Korobelnik, Jean-François; Holz, Frank G; Roider, Johann; Ogura, Yuichiro; Simader, Christian; Schmidt-Erfurth, Ursula; Lorenz, Katrin; Honda, Miki; Vitti, Robert; Berliner, Alyson J; Hiemeyer, Florian; Stemper, Brigitte; Zeitz, Oliver; Sandbrink, Rupert

    2014-01-01

    To evaluate the efficacy and safety of intravitreal aflibercept injections for treatment of macular edema secondary to central retinal vein occlusion (CRVO). A randomized, multicenter, double-masked phase 3 study. A total of 177 treatment-naive patients with macular edema secondary to CRVO were randomized in a 3:2 ratio. Patients received either 2-mg intravitreal aflibercept or sham injections every 4 weeks for 20 weeks. From week 24 to 48, the aflibercept group received aflibercept as needed (pro re nata [PRN]), and the sham group continued receiving sham injections. The primary efficacy end point was the proportion of patients who gained 15 letters or more in best-corrected visual acuity (BCVA) at week 24. This study reports week 52 results including the proportion of patients who gained 15 letters or more in BCVA and the mean change from baseline BCVA and central retinal thickness. Efficacy end points at week 52 were all exploratory. At week 52, the mean percentage of patients gaining 15 letters or more was 60.2% in the aflibercept group and 32.4% in the sham group (P = 0.0004). Aflibercept patients, compared with sham patients, had a significantly higher mean improvement in BCVA (+16.9 letters vs. +3.8 letters, respectively) and reduction in central retinal thickness (-423.5 μm vs. -219.3 μm, respectively) at week 52 (P < 0.0001 for both). Aflibercept patients received a mean of 2.5 injections (standard deviation, 1.7 injections) during PRN dosing. The most common ocular adverse events in the aflibercept group were related to the injection procedure or the underlying disease, and included macular edema (33.7%), increased intraocular pressure (17.3%), and eye pain (14.4%). Treatment with intravitreal aflibercept provided significant functional and anatomic benefits after 52 weeks as compared with sham. The improvements achieved after 6 monthly doses at week 24 largely were maintained until week 52 with as-needed dosing. Intravitreal aflibercept

  1. The effect of vitreomacular adhesion in exudative age-related macular degeneration on the results of ranibizumab intravitreal injection.

    PubMed

    Suzuki, Hiroyuki; Morishita, Seita; Kohmoto, Ryohsuke; Fukumoto, Masanori; Sato, Takaki; Kida, Teruyo; Ueki, Mari; Oku, Hidehiro; Nakamura, Kimitoshi; Ikeda, Tsunehiko

    2017-01-01

    To investigate whether vitreomacular adhesion (VMA) affects the outcome of anti-vascular endothelial growth factor (VEGF) therapy for the treatment of exudative age-related macular degeneration (AMD) in Japanese patients. Of 88 Japanese AMD patients (28 men and 60 women, mean age: 72.7±7.5 years) who underwent intravitreal injection of ranibizumab for 3 years from 2010 to 2013, this study involved 12 eyes of 12 patients (10 men and two women) in whom VMA was observed based on optical coherence tomography (OCT) findings (VMA [+] group) and 17 eyes of 16 patients (seven men and nine women, control group) in whom no VMA was observed (VMA [-] group). In all enrolled patients, ranibizumab was administered monthly for 3 months, and then administered as needed (ie, pro re nata) when deterioration was observed. The two groups were then compared in regard to changes in visual acuity (VA) and the frequency of ranibizumab administration over a 1-year period. No significant difference was found between the two groups in regard to the transformation of the mean logarithm of the minimum angle of resolution VA change after the first visit. Over the 1-year treatment, the mean frequency of ranibizumab administration for the VMA (+) group was 5.6±2.5 times and for the VMA (-) group was 3.8±1.1 times, thus illustrating a significant difference between the two groups (Mann-Whitney's U-test: P<0.05). Our findings show that the mean frequency of ranibizumab administration for the VMA (+) group was higher than that in the VMA (-) group, thus indicating that VMA might possibly be involved in the progress of AMD pathology.

  2. Distribution of Triamcinolone Acetonide after Intravitreal Injection into Silicone Oil-Filled Eye.

    PubMed

    Da, Ma; Li, Kenneth K W; Chan, Kevin C; Wu, Ed X; Wong, David S H

    2016-01-01

    There is increasing use of the vitreous cavity as a reservoir for drug delivery. We study the intraocular migration and distribution of triamcinolone acetonide (TA) after injection into silicone oil tamponade agent during and after vitrectomy surgery ex vivo (pig eye) and in vitro (glass bottle). For ex vivo assessment, intraocular migration of TA was imaged using real-time FLASH MRI scans and high-resolution T2W imaging and the in vitro model was monitored continuously with a video camera. Results of the ex vivo experiment showed that the TA droplet sank to the interface of silicone oil and aqueous almost immediately after injection and remained inside the silicone oil bubble for as long as 16 minutes. The in vitro results showed that, after the shrinkage of the droplet, TA gradually precipitated leaving only a lump of whitish crystalline residue inside the droplet for about 100 minutes. TA then quickly broke the interface and dispersed into the underlying aqueous within 15 seconds, which may result in a momentary increase of local TA concentration in the aqueous portion and potentially toxic to the retina. Our study suggests that silicone oil may not be a good candidate as a drug reservoir for drugs like TA.

  3. Distribution of Triamcinolone Acetonide after Intravitreal Injection into Silicone Oil-Filled Eye

    PubMed Central

    Wu, Ed X.; Wong, David S. H.

    2016-01-01

    There is increasing use of the vitreous cavity as a reservoir for drug delivery. We study the intraocular migration and distribution of triamcinolone acetonide (TA) after injection into silicone oil tamponade agent during and after vitrectomy surgery ex vivo (pig eye) and in vitro (glass bottle). For ex vivo assessment, intraocular migration of TA was imaged using real-time FLASH MRI scans and high-resolution T2W imaging and the in vitro model was monitored continuously with a video camera. Results of the ex vivo experiment showed that the TA droplet sank to the interface of silicone oil and aqueous almost immediately after injection and remained inside the silicone oil bubble for as long as 16 minutes. The in vitro results showed that, after the shrinkage of the droplet, TA gradually precipitated leaving only a lump of whitish crystalline residue inside the droplet for about 100 minutes. TA then quickly broke the interface and dispersed into the underlying aqueous within 15 seconds, which may result in a momentary increase of local TA concentration in the aqueous portion and potentially toxic to the retina. Our study suggests that silicone oil may not be a good candidate as a drug reservoir for drugs like TA. PMID:27493959

  4. Different Clinical Courses on Long-Term Follow-Up of Age-Related Macular Degeneration Patients Treated with Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

    PubMed

    Sagiv, Oded; Zloto, Ofira; Moroz, Iris; Moisseiev, Joseph

    2017-01-01

    To assess the long-term outcome of neovascular age-related macular degeneration (AMD) treated with multiple intravitreal anti-vascular endothelial growth factor (VEGF) injections. All patients treated with over 30 intravitreal anti-VEGF injections for neovascular AMD between 2007 and 2014 were retrospectively reviewed. A total of 67 eyes received 2,960 (mean 45 ± 9.1 per eye) anti-VEGF injections. Eyes with good final visual acuity (VA) had better initial VA (p = 0.020) and maintained it. Patients with moderate-to-poor final VA improved significantly after the first 3 monthly injections, and thereafter deteriorated consistently, mostly during the third (p = 0.019) and fourth (p = 0.006) years. Eyes with worse final VA had more intraretinal fluid (p = 0.05) and subretinal fibrosis (p = 0.04). Two distinct clinical courses were identified: good final VA was associated with initial and long-term stability of good VA; eyes with worse final VA had worse initial VA, progressive deterioration following the initial improvement, and more scarring and intraretinal fluid. This probably underscores the long-term benefits of early detection and treatment. © 2017 S. Karger AG, Basel.

  5. Multicenter, Randomized Clinical Trial to Assess the Effectiveness of Intravitreal Injections of Bevacizumab, Triamcinolone, or Their Combination in the Treatment of Diabetic Macular Edema.

    PubMed

    Neto, Hermelino O; Regatieri, Caio V; Nobrega, Mário J; Muccioli, Cristina; Casella, Antonio M; Andrade, Rafael E; Maia, Mauricio; Kniggendorf, Vinicius; Ferreira, Magno; Branco, André C; Belfort, Rubens

    2017-09-01

    To evaluate the efficacy of combined bevacizumab-triamcinolone intravitreal injection in the treatment of diabetic macular edema (DME) compared to monotherapy. At eight clinical sites, 111 patients with DME were randomly assigned to receive an intravitreal injection of bevacizumab (Avastin; Genentech, South San Francisco, CA), triamcinolone (Ophthalmos Pharmaceutical Industry, São Paulo-SP, Brazil), or their combination. The primary outcome was visual acuity (VA) at 6 months' follow-up. The average number of injections was 3.2 in the bevacizumab group, 2.4 in the combined group, and 2.1 in the triamcinolone group. All groups presented with improvements in VA (P < .001); however, no differences between groups were observed (P = .436). Mean reduction in central retinal thickness was statistically different only between the triamcinolone and bevacizumab groups (P < .015). Mono- or combination therapy was effective for DME treatment. No synergistic effects were observed; however, triamcinolone alone or a drug combination may reduce the number of injections required when compared to bevacizumab alone. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:734-740.]. Copyright 2017, SLACK Incorporated.

  6. Bromfenac alone or with single intravitreal injection of bevacizumab or triamcinolone acetonide for treatment of uveitic macular edema.

    PubMed

    Radwan, Alaa E; Arcinue, Cheryl A; Yang, Paul; Artornsombudh, Pichaporn; Abu Al-Fadl, Esam M; Foster, C Stephen

    2013-07-01

    To evaluate the efficacy of bromfenac drops alone or with a single intravitreal injection of bevacizumab (IVB) or triamcinolone acetonide (IVTA) in the treatment of uveitic macular edema (UME). Comparative case series. STUDY PARTICIPANT: Sixty-seven eyes (of 55 patients) with UME that received either bromfenac drops alone (n = 34), IVB plus bromfenac (n = 21) or IVTA plus bromfenac (n = 12). Chart review of patients at the Massachusetts Eye Research and Surgery Institution (MERSI) was done. Eyes that received either bromfenac drops alone (Br), IVB plus bromfenac (IVB/Br) or IVTA plus bromfenac (IVTA/Br), with follow-up of up to 3 months, were included. Visual acuity. There was no statistically significant effect seen in VA or CMT in the Br group, with 17 of 34 eyes (50 %) needing re-injection before 3 months of follow-up. Mean change in CMT at 4 weeks for the Br group was 5.06 µm. Compared to baseline, both the IVTA/Br and IVB/Br groups showed significant decrease in CMT and improvement in VA at 1 and 3 months follow-up. There was also a continuous decrease in CMT up to 3 months of follow-up with the IVTA/Br group, which was found to be significant in comparison with the IVB/Br group; this trend was not seen in the IVB/Br group at 3 months. The greatest mean change in CMT at 1 month was seen in the IVTA/Br group (154.33 ±178.22 µm), and this was statistically significant in comparison with the other groups (p = <0.0001). However, in terms of mean change in VA, there was no change in the Br group (0.01 ± 0.11 VA logMAR), and only 0.12 ± 0.19 and 0.15 ± 0.20 in the IVB/Br and IVTA/Br groups, respectively. IVB and IVTA are both effective in improving VA and decreasing CMT up to 3 months. Bromfenac is ineffective alone for UME treatment, but may have a synergistic effect with IVTA in reducing CMT up to 3 months of follow-up.

  7. [Interest of optical coherence tomography performed immediately before intravitreal injection of anti-VEGF in exudative AMD].

    PubMed

    Moyal, L; Cohen, S Y; Pedinielli, A; Semoun, O; Lalloum, F; Jung, C; Souied, E

    2015-09-01

    Two or three systematic intravitreal injections (IVT) may be prescribed in a PRN approach to treat an exudative recurrence of neovascular age-related macular degeneration (AMD), according to the phenotype. Optical coherence tomography (OCT) may be performed immediately before the 2nd or the 3rd scheduled IVT, making it possible to cancel the procedure in the absence of exudation. The aim of the study was to evaluate the usefulness of this OCT examination and to assess the percentage of IVT cancelled, in order to evaluate a potential medico-economic benefit. Monocentric retrospective study, in which were included 292 consecutive eyes with exudative recurrence of AMD, for which 2 or 3 IVT were scheduled between January 1st and April 30th, 2014. All patients received a first systematic IVT in the seven days following the diagnosis. Then, on the days of the 2nd and 3rd scheduled IVT, each patient had a visual acuity measurement and a Spectral domain-OCT (Spectralis, HRA Heidelberg Engineering). This measurement allowed for the IVT to be either performed as scheduled or cancelled. Both ranibizumab and aflibercept were used. A Chi(2) test was used to compare the qualitative variables and an adjusted Wilcoxon test for the quantitative values. Two hundred and ninety-two consecutive eyes were included; 172 in the "2 scheduled IVT" group (group A) and 120 in the "3 scheduled IVT" group (group B). At the first follow-up, 37.6% of scheduled IVT were cancelled after the OCT (44.1% in group A and 28.3% in group B). At the second follow-up, 33.3% of IVT were cancelled in group B. Overall, 150/412 (36.4%) IVT were avoided in this series. Presence of serous retinal detachment, retinal edema and increased central macular thickness were statistically correlated with confirmation of the scheduled IVT at the two follow-ups (P<0.001, P<0.001 and P=0.002, respectively). A savings of 429.80 € per patient was calculated during this short period of follow-up. An average non-injection

  8. DAPI diffusion after intravitreal injection of mesenchymal stem cells in the injured retina of rats.

    PubMed

    Castanheira, Paula; Torquetti, Leonardo Torquetti; Magalhãs, Débora Rodrigues Soares; Nehemy, Marcio B; Goes, Alfredo M

    2009-01-01

    To evaluate DAPI (4',6-diamidino-2-phenylindole) as a nuclear tracer of stem cell migration and incorporation it was observed the pattern of retinal integration and differentiation of mesenchymal stem cells (MSCs) injected into the vitreous cavity of rat eyes with retinal injury. For this purpose adult rat retinas were submitted to laser damage followed by transplantation of DAPI-labeled BM-MSCs grafts and double-labeled DAPI and quantum dot-labeled BM-MSCs. To assess a possible DAPI diffusion as well as the integration and differentiation of DAPI-labeled BM-MSCs in laser-injured retina, host retinas were evaluated 8 weeks after injury/transplantation. It was demonstrated that, 8 weeks after the transplant, most of the retinal cells in all neural retinal presented nuclear DAPI labeling, specifically in the outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL). Meanwhile, at this point, most of the double-labeled BM-MSCs (DAPI and quantum dot) remained in the vitreous cavity and no retinal cells presented the quantum dot marker. Based on these evidences we concluded that DAPI diffused to adjacent retinal cells while the nanocrystals remained labeling only the transplanted BM-MSCs. Therefore, DAPI is not a useful marker for stem cells in vivo tracing experiments because the DAPI released from dying cells in moment of the transplant are taken up by host cells in the tissue.

  9. Bilateral intravitreal ranibizumab injection and panretinal photocoagulation in a 16-year-old girl with severe vaso-occlusive lupus retinopathy.

    PubMed

    Doruk, Hasan Can; Cetin, Pinar; Onen, Fatos; Saatci, A Osman

    2013-01-01

    A 16-year-old girl with fever of unknown origin and bilateral vaso-occlusive retinopathy with retinal neovascularization, preretinal hemorrhage, and serous macular detachment was treated with single bilateral 0.5 mg intravitreal ranibizumab injection prior to aggressive PRP with success. No systemic steroids or immunosuppressive therapy was employed at that time. She received the diagnosis of "systemic lupus erythematosus" five years after this episode with further systemic symptoms. In certain cases with vaso-occlusive type of lupus retinopathy, anti-VEGF agents may be administered in addition to panretinal photocoagulation to achieve better visual and anatomic outcome.

  10. [Choroidal metastasis from a lung adenocarcinoma treated by intravitreal injection of anti-VEGF and external beam radiotherapy: A case report].

    PubMed

    Menoux, I; Guihard, S; Antoni, D; Bijon, J-C; Noël, G

    2017-03-23

    Choroidal metastases of lung cancer are very uncommon. This localization should be suspected on blurred vision and confirmed with an ophthalmological examination. Its treatment is not entirely codified. We report a case of blurred vision secondary to bilateral choroidal metastasis in a patient with choroidal metastases from a lung adenocarcinoma, treated by intravitreal anti-vascular endothelial growth factor (VEGF) injection and external beam radiotherapy. According to a literature review, we analyzed the place of the targeted treatments used alone or combined with the radiotherapy.

  11. Determination of triamcinolone acetonide in silicone oil and aqueous humor of vitrectomized rabbits' eyes: Application for a pharmacokinetic study with intravitreal triamcinolone acetonide injections (Kenalog® 40).

    PubMed

    Fernandes-Cunha, Gabriella M; Saliba, Juliana B; Siqueira, Rubens C; Jorge, Rodrigo; Silva-Cunha, Armando

    2014-02-01

    A simple and accurate method including liquid-liquid extraction and protein precipitation procedures from silicone oil and aqueous humor samples followed by high-performance liquid chromatography (HPLC-UV) was developed and validated to determine the pharmacokinetic profile of triamcinolone acetonide in silicone oil and aqueous humor of rabbits' eyes submitted to the pars plana vitrectomy surgery. The method was successfully applied to quantify the drug remaining in silicone oil and aqueous humor (LOQ range of 1μg/mL). The triamcinolone acetonide remained in silicone oil and aqueous humor of vitrectomized rabbits' eyes for four weeks after the intravitreal injections.

  12. [The results of intravitreal bevacizumab in high myopic subretinal neovascularisation].

    PubMed

    Branisteanu, D; Moraru, Andreea

    2013-01-01

    To asses the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization secondary to pathologic myopia; To asses the safety and results stability; Prospective, interventional case study of 18 eyes with choroidal neovascularization secondary to pathologic myopia treated with 1.25 mg. intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. Mean age of patients in the study was 43.86%--6.32 years (ranging 24-62 years). The mean number of intravitreal injections was 2.62%--0.53 (ranging between 1 - 4 injections). Mean visual acuity improved in all cases. An increase of more than 15 letters was noted in 44.44.% of the cases. OCT confirmed a reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the choroidal neovascularization reappeared in 5 cases (27.77%) requiring additional treatment. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the choroidal neovascularization secondary to pathologic myopia. More than 40% of the cases regained at least 3 lines in ETDRS chart but a recurrence was noted in 27.77% of the cases at 6 months.

  13. Intravitreal Injection of Ozurdex® Implant in Patients with Persistent Diabetic Macular Edema, with Six-Month Follow-Up

    PubMed Central

    Pacella, Fernanda; Ferraresi, Adriana Francesca; Turchetti, Paolo; Lenzi, Tommaso; Giustolisi, Rosalia; Bottone, Andrea; Fameli, Valeria; Romano, Maria Rosaria; Pacella, Elena

    2016-01-01

    AIM To evaluate the efficacy of intravitreal dexamethasone injections in diabetic macular edema (DME). METHODS A 700 μg slow-release intravitreal dexamethasone implant (Ozurdex®) was placed in the vitreal cavity of 17 patients (19 eyes) affected with persistent DME. Best corrected visual acuity (BCVA) was assessed through Early Treatment Diabetic Retinopathy Study (ETDRS). Central macular thickness (CMT) was measured by spectral-domain optical coherence tomography. BCVA and CMT examinations were carried out at baseline (T0) and repeated after three days, one month (T1), three months (T3), four months (T4), and six months (T6) post injection. RESULTS Dexamethasone implant induced an improvement in ETDRS at T1, T3, T4, and T6 post injection. CMT was reduced at T1, T3, and T4, while at T6, CMT values were not statistically different from baseline. No complications were observed during the follow-up. CONCLUSION Our data suggest that dexamethasone implant is effective in reducing DME symptoms within a six-month frame. PMID:27147895

  14. Effect of prophylactic intraocular pressure-lowering medication (brinzolamide) on intraocular pressure after ranibizumab intravitreal injection: A case-control study.

    PubMed

    Song, Shuang; Yu, Xiao-Bing; Dai, Hong

    2016-10-01

    To observe the effect of prophylactic intraocular pressure (IOP)-lowering medication (brinzolamide) on IOP after ranibizumab intravitreal injections (IVIs). This prospective case-control study included 352 eyes from 352 patients (1 eye per patient) who were treated with ranibizumab intravitreal injection and divided randomly into two groups. Two hundred and three patients in control group only received the ranibizumab IVI, but 149 patients in case group received one drop of prophylactic intraocular brinzolamide preinjection. The IOP was measured by noncontact tonometer before injection, at 10, 30, 120 min and 1 day after injection in a sitting position. The mean IOP measured before injection, at 10, 30, 120 min and 1 day after injection individually were 15.79 ± 2.21 mmHg, 19.33 ± 4.86 mmHg, 16.64 ± 2.93 mmHg, 16.17 ± 3.13 mmHg, and 15.07 ± 2.55 mmHg in case group and were 15.82 ± 2.57 mmHg, 21.34 ± 5.88 mmHg, 18.17 ± 4.06 mmHg, 17.59 ± 4.42 mmHg, and15.48 ± 2.92 mmHg in control group. Comparing two groups, the mean increase on IOP was statistically significant at 10, 30, 120 min postinjection (P < 0.05). IVI of ranibizumab causes a considerable short-term transient rise on IOP in most patients. The effect of prophylactic IOP-lowering medication on IOP after IVIs can be statistically significant from 10 min to 2 h after IVIs.

  15. Effect of prophylactic intraocular pressure-lowering medication (brinzolamide) on intraocular pressure after ranibizumab intravitreal injection: A case–control study

    PubMed Central

    Song, Shuang; Yu, Xiao-bing; Dai, Hong

    2016-01-01

    Purpose: To observe the effect of prophylactic intraocular pressure (IOP)-lowering medication (brinzolamide) on IOP after ranibizumab intravitreal injections (IVIs). Materials and Methods: This prospective case–control study included 352 eyes from 352 patients (1 eye per patient) who were treated with ranibizumab intravitreal injection and divided randomly into two groups. Two hundred and three patients in control group only received the ranibizumab IVI, but 149 patients in case group received one drop of prophylactic intraocular brinzolamide preinjection. The IOP was measured by noncontact tonometer before injection, at 10, 30, 120 min and 1 day after injection in a sitting position. Results: The mean IOP measured before injection, at 10, 30, 120 min and 1 day after injection individually were 15.79 ± 2.21 mmHg, 19.33 ± 4.86 mmHg, 16.64 ± 2.93 mmHg, 16.17 ± 3.13 mmHg, and 15.07 ± 2.55 mmHg in case group and were 15.82 ± 2.57 mmHg, 21.34 ± 5.88 mmHg, 18.17 ± 4.06 mmHg, 17.59 ± 4.42 mmHg, and15.48 ± 2.92 mmHg in control group. Comparing two groups, the mean increase on IOP was statistically significant at 10, 30, 120 min postinjection (P < 0.05). Conclusions: IVI of ranibizumab causes a considerable short-term transient rise on IOP in most patients. The effect of prophylactic IOP-lowering medication on IOP after IVIs can be statistically significant from 10 min to 2 h after IVIs. PMID:27905340

  16. Effect of prophylactic timolol 0.1% gel on intraocular pressure after an intravitreal injection of ranibizumab: a randomized study

    PubMed Central

    Pece, Alfredo; Allegrini, Davide; Montesano, Giovanni; Dimastrogiovanni, Andrea Fabio

    2016-01-01

    Purpose The purpose of this study is to make a prospective evaluation of the effect of timolol 0.1% eye gel on short-term intraocular pressure (IOP) after an intravitreal injection (IVI) of ranibizumab. Participants and methods One hundred and fifty eyes of 150 IVI-naïve patients with macular edema caused by various pathological conditions (age-related macular degeneration, central or branch retinal vein occlusion, and diabetic retinopathy) were scheduled to undergo an IVI of ranibizumab (0.5 mg/0.05 cc). The patients were randomly divided into three groups: 50 were not treated with timolol before the IVI (group 1); 50 received an instillation of timolol 0.1% eye gel the evening before the IVI (group 2); and 50 received an instillation of timolol 0.1% eye gel 2 hours before the IVI (group 3). The incidence of clinically significant intraocular hypertensive spikes (>25 mmHg and >40 mmHg) was then assessed. Results Our findings showed that mean IOP at baseline was significantly higher than at both 5 and 60 minutes after IVI (P<0.01). Spikes of >25 mmHg were recorded at either time in 27 patients (54%) in group 1, 23 patients (44%) in group 2, and 24 patients (48%) in group 3. None of the between-group differences were significant. Spikes of >40 mmHg (which were only detected 5 minutes after IVI) were recorded in nine (18%), eight (16%), and one patient (2%) in groups 1, 2, and 3, respectively. The only significant difference was between the control and group 3 (P=0.012). Conclusion An increase in IOP after antivascular endothelial growth factor IVI is a frequent complication. The prophylactic use of timolol 0.1% gel effectively reduced the mean IOP when administered 2 hours before IVI and was also effective in preventing dangerous IOP spikes of >40 mmHg. It is therefore recommended before IVIs as a means of preventing emergency procedures and preserving the health of the optic nerve. PMID:27382246

  17. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study.

    PubMed

    Heier, Jeffrey S; Clark, W Lloyd; Boyer, David S; Brown, David M; Vitti, Robert; Berliner, Alyson J; Kazmi, Husain; Ma, Yu; Stemper, Brigitte; Zeitz, Oliver; Sandbrink, Rupert; Haller, Julia A

    2014-07-01

    To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). Randomized, double-masked, phase 3 trial. A total of 188 patients with macular edema secondary to CRVO. Patients received IAI 2 mg (IAI 2Q4) (n = 114) or sham injections (n = 74) every 4 weeks up to week 24. During weeks 24 to 52, patients from both arms were evaluated monthly and received IAI as needed, or pro re nata (PRN) (IAI 2Q4 + PRN and sham + IAI PRN). During weeks 52 to 100, patients were evaluated at least quarterly and received IAI PRN. The primary efficacy end point was the proportion of patients who gained ≥ 15 letters in best-corrected visual acuity (BCVA) from baseline to week 24. This study reports week 100 results. The proportion of patients gaining ≥ 15 letters was 56.1% versus 12.3% (P<0.001) at week 24, 55.3% versus 30.1% (P<0.001) at week 52, and 49.1% versus 23.3% (P<0.001) at week 100 in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean change from baseline BCVA was also significantly higher in the IAI 2Q4 + PRN group compared with the sham + IAI PRN group at week 24 (+17.3 vs. -4.0 letters; P<0.001), week 52 (+16.2 vs. +3.8 letters; P<0.001), and week 100 (+13.0 vs. +1.5 letters; P<0.0001). The mean reduction from baseline in central retinal thickness was 457.2 versus 144.8 μm (P<0.001) at week 24, 413.0 versus 381.8 μm at week 52 (P = 0.546), and 390.0 versus 343.3 μm at week 100 (P = 0.366) in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean number (standard deviation) of PRN injections in the IAI 2Q4 + PRN and sham + IAI PRN groups was 2.7 ± 1.7 versus 3.9 ± 2.0 during weeks 24 to 52 and 3.3 ± 2.1 versus 2.9 ± 2.0 during weeks 52 to 100, respectively. The most frequent ocular serious adverse event from baseline to week 100 was vitreous hemorrhage (0.9% vs. 6.8% in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively). The

  18. Effects of apelin and vascular endothelial growth factor on central retinal vein occlusion in monkey eyes intravitreally injected with bevacizumab: a preliminary study

    PubMed Central

    Zhao, Tong; Lu, Qiang; Tao, Yong; Liang, Xiao-Ying; Wang, Kai

    2011-01-01

    Purpose To examine the intraocular distribution of bevacizumab at four weeks after intravitreal bevacizumab (IVB) injection and to investigate the effects of IVB on apelin and vascular endothelial growth factor (VEGF) in the central retinal vein occlusion (CRVO) of monkey eyes. Methods Direct laser coagulation was performed on all branch retinal veins in the right eyes of six Rhesus monkeys to establish a CRVO model. The eyes of the first three monkeys were enucleated one week, two weeks, and 24 weeks after the establishment of the CRVO model; this was the CRVO group. Subsequently, IVB was injected into the eyes of the last three monkeys one week, two weeks, and 24 weeks after laser coagulation; this was the IVB group. The left eye of the first monkey was used as normal control. Immunohistochemistry and reverse-transcription PCR was used to examine the expression of apelin and VEGF. The penetration of bevacizumab into the retina and iris was investigated by fluorescence immunostaining. Results Immunoreactivity for bevacizumab could be detected in the vessel walls of the iris and choroid on day 28 after injecting IVB: apelin and VEGF staining had been more prominent than normal in the CRVO eye, but these decreased following IVB injection. Expression of apelin mRNA (p<0.01) was lower in the IVB group than the CRVO group and did not vary significantly between groups. Conclusions Bevacizumab could be detected in the iris and choroid after four weeks of intravitreal injection. Apelin may be partially suppressed by bevacizumab, and it may play a role in retinal neovascularization during the development of CRVO. PMID:21552499

  19. Intravitreal memantine retinal toxicity in rabbits.

    PubMed

    Moreno Páramo, D; Reyna Vielma, S; Rodríguez Reyes, A; Hernández Ayuso, I; Quiroz Mercado, H

    2016-02-01

    To histologically evaluate whether the intravitreal application of memantine produces retinal toxicity in rabbits. A cross-sectional design, experimental, descriptive study was performed on 16 eyes of 16 New Zealand rabbits of 3 kg, divided in 4 groups of 4 rabbits. A dose of 70 ng/ml of intravitreal memantine was administered in Group A, a dose of 150 ng/ml in Group B, a dose of 400 ng/ml in Group C, and Group D received 1 ml of balanced salt solution. The injected eye of half of each group was enucleated 15 days after the injection, and the rest within 30 days after injection. Following enucleation, each eye was placed in 10% formaldehyde. Histopathological analysis was performed on all enucleated eyes. The animals were treated according to the guidelines of the Association for Research on Vision and Ophthalmology (ARVO). Groups A, B and D did not show any histopathological changes after their enucleation at 15 and 30 days. Group C showed changes in the photoreceptor layer after enucleation at 15 and 30 days. In our study, it was observed that memantine concentrations at 70 ng/ml and 150 ng/ml are safe when administered intravitreally; however, doses of 400 ng/ml produced retinal structural changes. This research should continue to assess its clinical usefulness. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Intravitreal Dexamethasone Implant (Ozurdex) in Coats’ Disease

    PubMed Central

    Saatci, Ali Osman; Doruk, Hasan Can; Yaman, Aylin

    2013-01-01

    We injected an intravitreal dexamethasone implant in two eyes of 2 pediatric patients with Coats’ disease in addition to other treatment modalities, such as intravitreal ranibizumab injection and indirect laser photocoagulation. In both eyes, intraocular pressure moderately rose in a temporary fashion. The dexamethasone implant seems to be a valuable addition to the armamentarium of treatment options for Coats’ disease as it necessitates fewer injections than anti-VEGF injections and thereby fewer sessions of general anesthesia in the pediatric population. PMID:24163679

  1. Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment.

    PubMed

    Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Duran, M Dolores; Pons-Vázquez, Sheila; Domingo-Pedro, Joan Carles; Díaz-Llopis, Manuel

    2014-01-01

    The purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period. Sixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0. Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl. Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases.

  2. Effects of Intravitreal Ranibizumab Injection on Chinese Patients with Wet Age-Related Macular Degeneration: 5-Year Follow-Up Results

    PubMed Central

    Lu, Yingyi; Huang, Jianfeng; Zhao, Jing; Long, Li

    2016-01-01

    Purpose. To observe the effect of intravitreal ranibizumab injection on wet age-related macular degeneration (wAMD) over 5 years in Chinese patients. Methods. Thirty-seven patients who were diagnosed with wAMD in our hospital from June 2007 to June 2014 were retrospectively reviewed. The PRN regimen and the treatment and extend regimen were applied. Best corrected visual acuity (BCVA), number of ranibizumab injections, and changes in the choroidal neovascularization (CNV) lesion over 5 years were analyzed. Results. The mean BCVA measured by the ETDRS chart at baseline was 47.4 and 5 years after the treatment it was 34.89 letters, which was significantly different (p = 0.013). Fourteen eyes (37.8%) had improved visual acuity after 5 years. The number of injections in 5 years was 11.53, and most of the injections were in the first two years. Seventeen (45.9%) cases developed fibrous lesions, and 2 (5.4%) cases had atrophic lesions after 5 years. The fibrosis/atrophy was significantly correlated with the injection numbers (Pearson, r = 0.663, and p = 0.000). Conclusion. Most of the patients can maintain visual acuity treated by ranibizumab in the first 3 years. After 5 years, some patients can still improve or maintain visual acuity. Fibrous scarring of the lesion is the main reason for a decrease in vision of wAMD patients. PMID:27885338

  3. Intravitreal bevacizumab injection alone or combined with triamcinolone versus macular photocoagulation in bilateral diabetic macular edema; application of bivariate generalized linear mixed model with asymmetric random effects in a subgroup of a clinical trial.

    PubMed

    Yaseri, Mehdi; Zeraati, Hojjat; Mohammad, Kazem; Soheilian, Masoud; Ramezani, Alireza; Eslani, Medi; Peyman, Gholam A

    2014-01-01

    To compare the efficacy of intravitreal bevacizumab (IVB) injection alone or with intravitreal triamcinolone acetonide (IVB/IVT) versus macular photocoagulation (MPC) in bilateral diabetic macular edema (DME). In this study we revisited data from a subset of subjects previously enrolled in a randomized clinical trial. The original study included 150 eyes randomized to three treatment arms: 1.25 mg IVB alone, combined injection of 1.25 mg IVB and 2 mg IVT, and focal or modified grid MPC. To eliminate the possible effects of systemic confounders, we selected fellow eyes of bilaterally treated subjects who had undergone different treatments; eventually 30 eyes of 15 patients were re-evaluated at baseline, 6, 12, 18, and 24 months. Using mixed model analysis, we compared the treatment protocols regarding visual acuity (VA) and central macular thickness (CMT). Improvement in VA in the IVB group was significantly greater compared to MPC at months 6 and 12 (P = 0.037 and P = 0.035, respectively) but this difference did not persist thereafter up to 24 months. Other levels of VA were comparable at different follow-up intervals (all P > 0.05). The only significant difference in CMT was observed in favor of the IVB group as compared to IVB/IVT group at 24 months (P = 0.048). Overall VA was superior in IVB group as compared to MPC up to 12 months. Although the IVB group showed superiority regarding CMT reduction over 24 months as compared to IVB/IVT group, it was comparable to the MPC group through the same period of follow up.

  4. Intravitreal Injection of Bevacizumab in Primary Vitrectomy to Decrease the Rate of Retinal Redetachment: A Randomized Pilot Study

    PubMed Central

    Tousi, Adib; Hasanpour, Hossein; Soheilian, Masoud

    2016-01-01

    Purpose: To evaluate the effect of intravitreal bevacizumab (IVB) as a surgical adjunct in prevention of proliferative vitreoretinopathy (PVR) after retinal detachment surgery. Methods: In this controlled, randomized pilot study, 27 patients with primary retinal detachment undergoing pars plana deep vitrectomy were included. Of these, 12 received IVB at the end of procedure. The anatomic success and best corrected visual acuity (BCVA) were compared to the control group at months 3 and 6 postoperatively. Results: At three month follow-up, 3 of 11 eyes (27.3%) had detached retinas in the IVB group versus 6 of 12 (50.0%) in the control group (P = 0.40). At six-month follow-up, 3 of 10 eyes (30%) had detached retinas in the IVB group versus 3 in 8 (37.5%) in the control group (P > 0.99). Mean logMAR BCVA improved significantly in both groups relative to baseline, but did not show a significant difference at three-and six-month follow-ups between the two groups. Conclusion: Our preliminary results show neither a benefit nor any harm from intervention in both anatomic and visual outcomes. Our results support conducting additional studies to evaluate the effect of intravitreal bevacizumab on postoperative PVR. PMID:27621784

  5. The effect and safety of intravitreal injection of ranibizumab and bevacizumab on the corneal endothelium in the treatment of diabetic macular edema.

    PubMed

    Guzel, Huseyin; Bakbak, Berker; Koylu, Mehmet Talay; Gonul, Saban; Ozturk, Banu; Gedik, Sansal

    2017-03-01

    To investigate the effect and safety of intravitreal injection (IVI) of bevacizumab and ranibizumab on corneal endothelial cell count and morphology in patients with diabetic macular edema. A total of 60 eyes from 60 consecutive patients who received 0.5 mg/0.05 ml IVIs of bevacizumab (n = 30, IVB group) or 1.25 mg/0.05 ml ranibizumab (n = 30, IVR group) for three consecutive months were investigated prospectively. Specular microscopy was performed to evaluate endothelial cell count, the percentage of hexagonal cells (pleomorphism), and the coefficient of variation of the cell size (polymegathism); optical biometry was performed to evaluate central corneal thickness. Results before injection and 1 month after the first and third injections were compared. The groups were matched for age (p = 0.11) and gender (p = 0.32). There was no significant difference in endothelial cell count (IVB group, p = 0.66; IVR group, p = 0.74), pleomorphism (IVB group, p = 0.44; IVR group, p = 0.88) and polymegathism (IVB group, p = 0.21; IVR group, p = 0.24) before injection or 1 month after the first and third injections. There was also no difference in central corneal thickness (IVB group, p = 0.15; IVR group, p = 0.58) before injection or 1 month after the first and third injections. Monthly 1.25 mg/0.05 ml IVIs of bevacizumab or 0.5 mg/0.05 ml of ranibizumab for three consecutive months in the treatment of diabetic macular edema does not affect corneal morphology and has no harmful effects on the endothelium.

  6. Sustained Elevation of Intraocular Pressure Associated with Intravitreal Administration of Anti-vascular Endothelial Growth Factor: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhou, Yandan; Zhou, Minwen; Xia, Shigang; Jing, Qiancheng; Gao, Ling

    2016-01-01

    This study aimed to assess whether repetitive intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) cause sustained elevation of intraocular pressure (SE-IOP). We conducted a systematic review and meta-analysis based on five randomized controlled trials (RCTs) assessing 1428 subjects and 17 non-RCTs evaluating 8358 cases. In the RCTs, an increased risk of SE-IOP was found in the anti-VEGF group (summary risk ratio [RR] = 3.00, 95% confidence interval [CI]: 1.63–5.53) compared with the sham injection or laser group. The increased risk of SE-IOP was correlated with follow-up duration (RR = 2.14, 95% CI 0.69–6.57 at 6 months; RR = 3.15, 95% CI 0.99–10.09 at 12 months; RR = 3.48, 95% CI 1.38–8.78 at 23 months). The risk of SE-IOP after non-exclusion of pre-existing glaucoma patients (RR = 3.48, 95% CI 1.38–8.78) was higher than that obtained after excluding pre-existing glaucoma patients (RR = 2.6, 95% CI 1.16–5.81). In non-RCTs, the pooled prevalence of SE-IOP was 4.7% (95% CI 3.7–5.8) regardless of diagnosis criteria. In conclusion, repeated intravitreal injections of anti-VEGF agents cause a 2-fold elevation in SE-IOP risk. PMID:28000707

  7. Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina.

    PubMed

    Beltran, William A; Wen, Rong; Acland, Gregory M; Aguirre, Gustavo D

    2007-04-01

    Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 microg of CNTF in the left eye. The right eye served as a control and was injected with a similar volume of phosphate buffered saline (PBS). Ocular examinations were performed regularly during the treatment periods. At termination, the dogs were euthanatized, eyes collected and the retinas were processed for embedding in optimal cutting temperature (OCT) medium. The outer nuclear layer (ONL) thickness was evaluated on H&E sections and values in both CNTF- and PBS-treated eyes were compared. Morphologic alterations in the peripheral retina were characterized by immunohistochemistry using cell-specific markers. Cell proliferation in the retinas was examined on semi-thin plastic sections, and by BrdU pulse-labeling and Ki67 immunohistochemistry on cryosections. All CNTF-treated eyes showed early clinical signs of corneal epitheliopathy, subcapsular cataracts and uveitis. No statistically significant difference in ONL thickness was seen between the CNTF- and PBS-injected eyes. Prominent retinal remodeling that consisted in an abnormal increase in the number of rods, and in misplacement of some rods, cones, bipolar and Müller cells, was observed in the peripheral retina of CNTF-treated eyes. This was only seen when CNTF was in injected before the age at which the canine retina reaches full maturation. In XLPRA2 dogs, intravitreal injections of CNTF failed to prevent photoreceptors from undergoing cell death in the

  8. Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina

    PubMed Central

    Beltran, William A.; Wen, Rong; Acland, Gregory M.; Aguirre, Gustavo D.

    2009-01-01

    Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 μg of CNTF in the left eye. The right eye served as a control and was injected with a similar volume of phosphate buffered saline (PBS). Ocular examinations were performed regularly during the treatment periods. At termination, the dogs were euthanatized, eyes collected and the retinas were processed for embedding in optimal cutting temperature (OCT) medium. The outer nuclear layer (ONL) thickness was evaluated on H&E sections and values in both CNTF- and PBS-treated eyes were compared. Morphologic alterations in the peripheral retina were characterized by immunohistochemistry using cell-specific markers. Cell proliferation in the retinas was examined on semi-thin plastic sections, and by BrdU pulse-labeling and Ki67 immunohistochemistry on cryosections. All CNTF-treated eyes showed early clinical signs of corneal epitheliopathy, subcapsular cataracts and uveitis. No statistically significant difference in ONL thickness was seen between the CNTF- and PBS-injected eyes. Prominent retinal remodeling that consisted in an abnormal increase in the number of rods, and in misplacement of some rods, cones, bipolar and Müller cells, was observed in the peripheral retina of CNTF-treated eyes. This was only seen when CNTF was in injected before the age at which the canine retina reaches full maturation. In XLPRA2 dogs, intravitreal injections of CNTF failed to prevent photoreceptors from undergoing cell death in the

  9. Two-Year Outcomes of a Treat-and-Extend Regimen Using Intravitreal Aflibercept Injections for Typical Age-Related Macular Degeneration.

    PubMed

    Ito, Arisa; Matsumoto, Hidetaka; Morimoto, Masahiro; Mimura, Kensuke; Akiyama, Hideo

    2017-01-01

    The aim of this study was to evaluate the efficacy of a treat-and-extend (TAE) regimen using intravitreal injection of aflibercept (IVA) for typical age-related macular degeneration (tAMD). We retrospectively studied 61 treatment-naïve eyes with tAMD. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of injections, and complications during 2 years were evaluated. BCVA significantly improved by on average 0.13 logMAR units, and CMT and CCT significantly decreased after 2 years. The number of injections was on average 13.6. In the second year, eyes with classic choroidal neovascularization (CNV) needed significantly fewer treatments than eyes with occult CNV. Fourteen eyes, which developed subfoveal fibrosis, showed significantly poorer BCVA after 2 years. Subfoveal fibrosis was significantly common in classic CNV. A TAE regimen using IVA for tAMD might be effective for improving BCVA and exudative changes. The exudation may be suppressed with fewer treatments in classic CNV compared to occult CNV. © 2017 S. Karger AG, Basel.

  10. Sustained intraocular pressure elevation in eyes treated with intravitreal injections of anti-vascular endothelial growth factor for diabetic macular edema in a real-life setting.

    PubMed

    Vo Kim, S; Fajnkuchen, F; Sarda, V; Qu-Knafo, L; Bodaghi, B; Giocanti-Aurégan, A

    2017-08-22

    The aim of this study was to investigate the sustained intraocular pressure (IOP) elevation after repeated anti-VEGF intravitreal injections (IVI) in patients with diabetic macular edema (DME). A retrospective study included 140 eyes without prior glaucoma, treated with at least three anti-VEGF injections for DME between 2012 and 2016. IOP elevation was defined by an increase above baseline IOP by ≥6 mmHg. Baseline IOP was defined as the mean of IOP values before treatment initiation. Three groups were differentiated: group 1 without IOP elevation, groups 2 and 3 with IOP elevation and IOP <21 mmHg (group 2) and ≥21 mmHg (group 3). Rate and several risk factors of IOP elevation were assessed and compared between the three groups. IOP elevation occurred in ten eyes (7.1%). IOP was <21 mmHg in six eyes and ≥21 mmHg in four eyes. Statistically significant associations were found between IOP elevation and the number of injections, and HbA1c level. Two patients required local hypotonic treatment. In a real-life setting, we confirmed in eyes with center-involved DME without prior glaucoma or IOP elevation that repeated anti-VEGF IVI may increase the risk of sustained IOP elevation in about 7% of eyes.

  11. Local and systemic responses following intravitreous injection of AAV2-encoded modified Volvox channelrhodopsin-1 in a genetically blind rat model.

    PubMed

    Sugano, E; Tabata, K; Takahashi, M; Nishiyama, F; Shimizu, H; Sato, M; Tamai, M; Tomita, H

    2016-02-01

    We previously designed a modified channelrhodopsin-1 (mVChR1) protein chimera with a broader action than that of Chlamydomonas channelrhodopsin-2 and reported that its transduction into retinal ganglion cells can restore visual function in genetically blind, dystrophic Royal College of Surgeons (RCS) rats, with photostimuli ranging from 486 to 640 nm. In the current study, we sought to investigate the safety and influence of mVChR1 transgene expression. Adeno-associated virus type 2 encoding mVChR1 was administered by intravitreous injection into dystrophic RCS rats. Reverse-transcription PCR was used to monitor virus and transgene dissemination and the results demonstrated that their expression was restricted specifically within the eye tissues, and not in non-target organs. Moreover, examination of the blood, plasma and serum revealed that no excess immunoreactivity was present, as determined using standard clinical hematological parameters. Serum antibodies targeting the recombinant adeno-associated virus (rAAV) capsid increased after the injection; however, no increase in mVChR1 antibody was detected during the observation period. In addition, retinal histological examination showed no signs of inflammation in rAAV-injected rats. In conclusion, our results demonstrate that mVChR1 can be exogenously expressed without harmful immunological reactions in vivo. These findings will aid in studies of AAV gene transfer to restore vision in late-stage retinitis pigmentosa.

  12. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial.

    PubMed

    Heier, Jeffrey S; Kherani, Saleema; Desai, Shilpa; Dugel, Pravin; Kaushal, Shalesh; Cheng, Seng H; Delacono, Cheryl; Purvis, Annie; Richards, Susan; Le-Halpere, Annaig; Connelly, John; Wadsworth, Samuel C; Varona, Rafael; Buggage, Ronald; Scaria, Abraham; Campochiaro, Peter A

    2017-07-01

    Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA. Patients were assigned to each cohort in order of enrolment, with the first three patients being assigned to and completing the first cohort before filling positions in the following treatment groups. Patients aged 50 years or older with neovascular age-related macular degeneration and a baseline best-corrected visual acuity score of 20/100 or less in the study eye were enrolled in four dose-ranging cohorts (cohort 1, 2 × 10(8) vector genomes (vg); cohort 2, 2 × 10(9) vg; cohort 3, 6 × 10(9) vg; and cohort 4, 2 × 10(10) vg, n=3 per cohort) and one maximum tolerated dose cohort (cohort 5, 2 × 10(10) vg, n=7) and followed up for 52 weeks. The primary objective of the study was to assess the safety and tolerability of a single intravitreous injection of AAV2-sFLT01, through the measurement of eye-related adverse events. This trial is registered with ClinicalTrials.gov, number NCT01024998. 19 patients with advanced neovascular age-related macular degeneration were enrolled in the study between May 18, 2010, and July 14, 2014. All patients completed the 52-week trial period. Two patients in cohort 4 (2 × 10(10) vg) experienced adverse events that were possibly study-drug related: pyrexia and intraocular inflammation that resolved with a topical steroid. Five of ten patients who received 2 × 10(10) vg had aqueous humour concentrations of sFLT01 that peaked at 32·7-112·0 ng/mL (mean 73·7 ng/mL, SD 30·5) by week 26 with a slight

  13. Comparison of Suprachoroidal Drug Delivery with Subconjunctival and Intravitreal Routes Using Noninvasive Fluorophotometry

    PubMed Central

    Tyagi, Puneet; Kadam, Rajendra S.; Kompella, Uday B.

    2012-01-01

    Purpose To determine whether exposure of sodium fluorescein (NaF) to the choroid-retina region in the posterior segment of the eye is greater with suprachoroidal injection when compared to intravitreal and transscleral routes. Methods Suprachoroidal injection, a new approach for drug delivery to the posterior segment of the eye was validated using a 34 G needle and Indian ink injections in Sprague Dawley rats, followed by histology. Delivery of NaF was compared in Sprague Dawley rats after suprachoroidal, posterior subconjunctival, or intravitreal injections. NaF levels were monitored noninvasively up to 6 hours using Fluorotron Master™, an ocular fluorophotometer Pharmacokinetic parameters were estimated using WinNonlin. Results Histological analysis indicated localization of India ink to the suprachoroidal space below sclera, following injection. NaF delivery to choroid-retina was in the order: suprachoroidal > intravitreal >posterior subconjunctival injection. Peak NaF concentration (Cmax) in choroid-retina was 36-fold (p = 0.001) and 25-fold (p = 0.001) higher after suprachoroidal (2744±1111 ng/ml) injection when compared to posterior subconjunctival (76±6 ng/ml) and intravitreal (108±39 ng/ml) injections, respectively. NaF exposure (AUC0–360min) to choroid-retina after suprachoroidal injection was 6-fold (p = 0.001) and 2-fold (p = 0.03) higher than posterior subconjunctival and intravitreal injections, respectively. Choroid-retina Tmax was observed immediately after dosing with suprachoroidal injections and at 10 and 27.5 minutes, respectively, with subconjunctival and intravitreal injections. Conclusions Suprachoroidal injections are feasible in a rat model. Suprachoroidal injections resulted in the highest bioavailability, that is, the extent and rate of delivery of NaF to choroid-retina, when compared to intravitreal and posterior subconjunctival injections. Ocular fluorophotometry is useful for noninvasive monitoring of NaF in rats

  14. Comparison between "early" or "late" intravitreal injection of dexamethasone implant in branch (BRVO) or central (CRVO) retinal vein occlusion: six-months follow-up.

    PubMed

    Pacella, Fernanda; La Torre, Giuseppe; Basili, Stefania; Autolitano, Monica; Pascarella, Antonella; Lenzi, Tommaso; Pacella, Elena

    2017-09-01

    The aim of this study was to compare early and late injections of intravitreal dexamethasone implant in patients affected by central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) with a six-months follow-up. We assessed whether an earlier treatment start (within seven days from diagnosis) could be more beneficial than a delayed (or late) treatment start (after seven days). The study included 81 patients (81 eyes) affected by retinal vein occlusion. Best corrected visual acuity was assessed through Early Treatment Diabetic Retinopathy Study (ETDRS) while central macular thickness (CMT) was measured by spectral-domain optical coherence tomography. Both types of patients had a positive therapeutic response to dexamethasone, with an increase in visual acuity (ETDRS) and CMT reduction. CRVO patients were characterized by lower ETDRS values at baseline and at the end of the follow-up as compared to BRVO. CRVO patients showed higher CMT values at baseline, after three and six months from injection. No significant differences in therapeutic response to dexamethasone were observed between patients treated early or late, regardless of RVO type. This study demonstrates that the therapeutic properties of dexamethasone implant are not significantly influenced by an early or late treatment start in patients affected by BRVO and CRVO, although its therapeutic efficacy seems greater in the former type.

  15. Nurse-administered intravitreal injections of anti-VEGF: study protocol for noninferiority randomized controlled trial of safety, cost and patient satisfaction.

    PubMed

    Austeng, Dordi; Morken, Tora Sund; Bolme, Stine; Follestad, Turid; Halsteinli, Vidar

    2016-10-01

    Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) now improve or stabilize visual acuity in a number of previously untreatable eye diseases, of which the main are age-related macular degeneration, retinal vein occlusion and diabetic macular edema. Most patients require multiple injections over lengthy periods of time and the prevalence of treatable conditions is increasing. Anti-VEGF IVI normally administered by physicians, therefore represent a considerable workload on ophthalmologic clinics and will continue to do so in the near future. Nurse-administered IVI may relieve this workload, but the safety, cost and patient satisfaction of such an extended role for nurses in ophthalmologic clinics has not earlier been investigated. To investigate these outcomes following independent anti-VEGF IVI by trained nurses, a noninferiority randomized controlled trial is being conducted. Patients eligible for anti-VEGF treatment, minimum 304, are recruited and randomized to IVI administration by either trained nurses or physicians. The primary outcome is safety, measured by difference in mean change in visual acuity between the two groups during an observation period of 12 months. Secondary outcomes are incidence of ocular adverse events, cost per patient and patient satisfaction. This study protocol describes the design of the first randomized controlled trial of nurse-administered IVI of anti-VEGF. The study is designed to examine safety, cost and patient satisfaction during 12 months follow-up. ClinicalTrials.gov NCT02359149 . Registered February 4, 2015.

  16. The effect of laser pan-retinal photocoagulation with or without intravitreal bevacizumab injections on the OCT-measured macular choroidal thickness of eyes with proliferative diabetic retinopathy

    PubMed Central

    Preti, Rony C; Mutti, Anibal; Ferraz, Daniel A; Zacharias, Leandro C; Nakashima, Yoshitaka; Takahashi, Walter Y; Monteiro, Mario L R

    2017-01-01

    OBJECTIVES: To investigate the effect of laser pan-retinal photocoagulation with or without intravitreal bevacizumab injections on macular choroidal thickness parameters in eyes with high-risk proliferative diabetic retinopathy. METHODS: High-risk proliferative diabetic retinopathy patients undergoing laser treatment were prospectively enrolled in this study. One eye was randomly selected for laser treatment combined with bevacizumab injections, study group, whereas the corresponding eye was subjected to laser treatment alone, control group. Spectral-domain optical coherence tomography with enhanced depth imaging was used to measure the macular choroidal thickness prior to and 1 month after treatment. Measurements in both groups were compared. Clinicaltrials.gov: NCT01389505. RESULTS: Nineteen patients (38 eyes) with a mean±standard deviation age of 53.4±9.3 years were evaluated, and choroidal thickness measurements for 15 patients were used for comparison. The greatest measurement before treatment was the subfoveal choroidal thickness (341.68±67.66 μm and 345.79±83.66 μm for the study and control groups, respectively). No significant difference between groups was found in terms of macular choroidal thickness measurements at baseline or after treatment. However, within-group comparisons revealed a significant increase in choroidal thickness parameters in 10 measurements in the study group and in only 5 temporal measurements in the control group when 1-month follow-up measurements were compared to baseline values. CONCLUSIONS: The macular choroidal thickness does not appear to be significantly influenced by laser treatment alone but increases significantly when associated with bevacizumab injections in patients with proliferative diabetic retinopathy and macular edema. Because bevacizumab injections reduce short-term laser pan-retinal photocoagulation-induced macular edema, our findings suggest that the choroid participates in its pathogenesis. PMID:28273240

  17. Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data.

    PubMed

    Del Amo, Eva M; Urtti, Arto

    2015-08-01

    Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Effect of choroidal perfusion on ocular tissue distribution after intravitreal or suprachoroidal injection in an arterially perfused ex vivo pig eye model.

    PubMed

    Abarca, Eva M; Salmon, Jacklyn H; Gilger, Brian C

    2013-10-01

    To compare tissue distribution of dye-drug surrogates after intravitreal (IVT) and suprachoroidal (SCS) delivery to determine the influence of drug lipophilicity and choroidal circulation. Thirty-two pig eyes were collected immediately after euthanasia. Sixteen eyes were perfused for 30 min through one long posterior ciliary artery with nondye containing nutrient media. An IVT or SCS injection was performed with either a 100 μL balanced salt solution (BSS, n=8), 1% sodium fluorescein (NaF, n=12) or 0.12% lipophilic carbocyanine dye (DiI, n=12). Globes were maintained at 37°C for 15 min, and then snap-frozen and dissected. Aqueous extraction and measurement of NaF or DiI concentration was performed using spectrophotometry and spectrofluorometry, respectively. After SCS delivery of NaF scleral, iris-ciliary body, choroidal and vitreous dye levels were higher in nonperfused eyes compared to perfused eyes. After DiI SCS or IVT delivery, no significant differences were found in dye tissue concentrations in perfused eyes compared to nonperfused eyes. Following perfusion, a better and even drug distribution was found in the retinal pigmented epithelium (RPE)-choroid following IVT and SCS delivery of the hydrophilic drug and after IVT injection of the lipophilic drug compared to nonperfused eyes. Choroidal circulation reduces the tissue drug concentration of the hydrophilic drug suggesting an early clearance mechanism after SCS delivery. SCS injections of lipid and hydrophilic drugs allowed direct drug delivery to the retina and RPE-choroid with limited exposition to the anterior segment.

  19. Efficacy and safety of two or more dexamethasone intravitreal implant injections for treatment of macular edema related to retinal vein occlusion (Shasta study).

    PubMed

    Capone, Antonio; Singer, Michael A; Dodwell, David G; Dreyer, Richard F; Oh, Kean T; Roth, Daniel B; Walt, John G; Scott, Lanita C; Hollander, David A

    2014-02-01

    To evaluate the efficacy, safety, and reinjection interval of dexamethasone intravitreal implant (DEX implant) in branch retinal vein occlusion and central retinal vein occlusion patients receiving ≥ 2 DEX implant treatments. Multicenter (26-site), retrospective chart review study. Data were collected from baseline (at first DEX implant) through 3 months to 6 months after last DEX implant. Patients (n = 289) received 2 to 9 (mean, 3.2) DEX implants as monotherapy (29.1% of patients) or with adjunctive treatments/procedures. Mean duration of macular edema before first DEX implant was 18.4 months. Mean reinjection interval was 5.6 months. Mean peak change in best-corrected visual acuity from baseline through 4 weeks to 20 weeks after final DEX implant was +1.0 line (P < 0.001). Best-corrected visual acuity and central retinal thickness improved significantly from baseline after each of the first 6 DEX implant injections (P ≤ 0.037); 59.7% of branch retinal vein occlusion and 66.7% of central retinal vein occlusion patients achieved ≥ 2-line best-corrected visual acuity improvement. Intraocular pressure increase (≥ 10 mmHg) occurred in 32.6% of patients; 29.1% used intraocular pressure-lowering medication to treat increases associated with DEX implant. Only 1.7% of patients required incisional glaucoma surgery. Retinal vein occlusion patients treated with multiple DEX implant injections, either alone or combined with other therapies, had improved central retinal thickness and visual acuity with each subsequent injection. No new safety concerns developed with multiple implants.

  20. Neuroprotective and antiapoptotic activity of lineage-negative bone marrow cells after intravitreal injection in a mouse model of acute retinal injury.

    PubMed

    Machalińska, Anna; Rogińska, Dorota; Pius-Sadowska, Ewa; Kawa, Miłosz P; Paczkowska, Edyta; Rudnicki, Michał; Lejkowska, Renata; Baumert, Bartłomiej; Wiszniewska, Barbara; Machaliński, Bogusław

    2015-01-01

    We investigated effects of bone marrow-derived, lineage-negative cell (Lin(-)BMC) transplantation in acute retinal injury. Lin(-)BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin(-)BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin(-)BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin(-)BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin(-)BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors.

  1. Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA.

    PubMed

    Hsu, Min-Yen; Hung, Yu-Chien; Hwang, De-Kuang; Lin, Shang-Chi; Lin, Keng-Hung; Wang, Chun-Yuan; Choi, Hin-Yeung; Wang, Yu-Ping; Cheng, Chao-Min

    2016-10-11

    Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies.

  2. Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA

    PubMed Central

    Hsu, Min-Yen; Hung, Yu-Chien; Hwang, De-Kuang; Lin, Shang-Chi; Lin, Keng-Hung; Wang, Chun-Yuan; Choi, Hin-Yeung; Wang, Yu-Ping; Cheng, Chao-Min

    2016-01-01

    Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies. PMID:27725716

  3. Bilateral Severe Sterile Inflammation with Hypopyon after Simultaneous Intravitreal Triamcinolone Acetonide and Aflibercept Injection in a Patient with Bilateral Marked Rubeosis Associated with Ocular Ischemic Syndrome

    PubMed Central

    Durmaz Engin, Ceren; Ayhan, Ziya; Men, Süleyman

    2017-01-01

    We report the clinical course of a diabetic patient with bilateral cataract and rubeosis in association with ocular ischemic syndrome and initially treated him with simultaneous intravitreal 2 mg aflibercept and 2 mg triamcinolone acetonide injection at the same setting prior to planned cataract surgery and further photocoagulation. However, sterile anterior segment inflammation characterized by hypopyon occurred four days apart in OU. Right eye developed the sterile inflammation at the third postinjection day and the left eye developed the sterile inflammation at the seventh postinjection day (two days after the uneventful cataract surgery with intraocular lens implantation) without any pain or significant redness. Vitreous biopsy taken during the right phacovitrectomy was negative for any microbial contamination. Both eyes were treated successfully with intensive topical prednisolone acetate with a relatively good visual outcome. It is likely that underlying ocular ischemic syndrome might have facilitated the formation of sterile inflammation as blood-aqueous barrier disruption and flare have already been present. PMID:28386497

  4. Neuroprotective and Antiapoptotic Activity of Lineage-Negative Bone Marrow Cells after Intravitreal Injection in a Mouse Model of Acute Retinal Injury

    PubMed Central

    Machalińska, Anna; Pius-Sadowska, Ewa; Kawa, Miłosz P.; Paczkowska, Edyta; Rudnicki, Michał; Lejkowska, Renata; Baumert, Bartłomiej; Wiszniewska, Barbara; Machaliński, Bogusław

    2015-01-01

    We investigated effects of bone marrow-derived, lineage-negative cell (Lin−BMC) transplantation in acute retinal injury. Lin−BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin−BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin−BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin−BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin−BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors. PMID:25810725

  5. The Comparative Efficiency of Intraperitoneal and Intravitreous Injection of Hydrogen Rich Saline against N-Methyl-N-Nitrosourea Induced Retinal Degeneration: A Topographic Study.

    PubMed

    Tao, Ye; Chen, Tao; Fang, Wei; Yan, Zhongjun; Yang, Qinghua; Huang, Yifei; Yu, Linjun; Fan, Lingling

    2017-01-01

    Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal diseases leading to blindness. The present study explored the protective effects of hydrogen rich saline (HRS) against the photoreceptor degeneration in the N-Methyl-N-nitrosourea (MNU) administrated rat, a pharmacologically induced RP model. The therapeutic effects of intraperitoneal (IP) and intravitreous (IV) injections of HRS on regional retina was quantified via topographic measurements. The MNU administrated rats received IV or IP injections of HRS, and then they were subjected to electroretinography, multi electrode array, histological and immunohistochemistry examinations. The concentrations of the retinal malondialdehyde (MDA), superoxide dismutase (SOD), as well as the mRNA levels of apoptotic-associated genes were quantified. The IP and IV delivery pathways of HRS were both effective to ameliorate MNU induced photoreceptor degeneration. Moreover, the IV acted as a more efficient delivery method than the IP in terms of therapeutic effects. Particularly, the topographic measurements suggested that the IV delivery of HRS could alleviate MNU induced photoreceptor degeneration in the posterior retina. The immunostaining experiments also verified the comparative efficiency between IV and IP delivery of HRS on regional cone photoreceptors. Focal cone photoreceptors showed different susceptibilities to HRS and exhibited as a distinct spatial disequilibrium: cone photoreceptors in the ST quadrant were preferentially rescued; meanwhile, HRS induced protection was feeblest in the IN quadrant. Furthermore, the HRS treatment increased the level of retinal SOD, while reduce the level of retinal MDA in MNU administered rats. The expression levels of sever apoptotic -associated genes were significantly altered by HRS treatment. Collectively, these findings suggest that the IV space is an excellent target for HRS delivery. The IV delivery of HRS can efficiently alleviate the photoreceptors

  6. BETTER PROGNOSIS FOR EYES WITH PRESERVED FOVEAL DEPRESSION AFTER INTRAVITREAL RANIBIZUMAB INJECTION FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.

    PubMed

    Kitagawa, Shuta; Yasuda, Shunsuke; Ito, Yasuki; Ueno, Shinji; Iwase, Takeshi; Terasaki, Hiroko

    2017-05-18

    To determine the prognosis of eyes with central retinal vein occlusion that had a preserved foveal depression at the baseline and were treated by intravitreal ranibizumab injections (IRIs). The authors reviewed the medical records of 23 eyes of 23 consecutive treatment-naive patients who received IRIs to treat the macular edema due to central retinal vein occlusion. Eyes were classified by the pre-IRI presence or absence of a foveal depression. A foveal depression was defined as a central foveal thickness that was <50 μm thinner than the average thickness at 200 μm temporal and nasal to the central fovea. The characteristics of the two groups were compared. Seven of 23 eyes had a preserved foveal depression before the IRI. The mean number of injections within 12 months after the initial IRI was significantly fewer (P < 0.001) in eyes with foveal depression (1.6 ± 0.5) than in eyes without foveal depression (4.3 ± 1.3). The mean best-corrected visual acuity at 12 months after the initial IRI was significantly better (P = 0.003) in eyes with foveal depression (0.10 ± 0.17 logarithm of the minimum angle of resolution [logMAR] units; 20/25 Snellen units) than in eyes without foveal depression (0.77 ± 0.54 logMAR units; 20/118 Snellen units). These results indicate that the prognosis is better for eyes with a foveal depression before the IRI treatment for a macular edema secondary to central retinal vein occlusion.

  7. Severe Ocular Inflammation Following Ranibizumab or Aflibercept Injections for Age-Related Macular Degeneration: A Retrospective Claims Database Analysis

    PubMed Central

    Souied, Eric H.; Dugel, Pravin U.; Ferreira, Alberto; Hashmonay, Ron; Lu, Jingsong; Kelly, Simon P.

    2016-01-01

    ABSTRACT Purpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept. Methods: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections. Results: The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91–1.21, vs. 0.64/1000 injections, 95% CI 0.54–0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment. Conclusions: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring

  8. Location of a Dexamethasone Implant at the Macula after Intravitreal Injection in a Silicone Oil-Filled Eye

    PubMed Central

    Esenulku, Cenap Mahmut

    2016-01-01

    Here, we report a case with cystoid macular edema (CME) due to central retinal vein occlusion (CRVO) presented with a dexamethasone implant (Ozurdex) trapped at the macula in her silicone oil- (SO-) filled eye after injection. No additional complications such as intraocular pressure (IOP) rise or retinal damage were observed. The CME was resolved during the follow-up period. At the last visit, 3 months following the injection, Ozurdex implant was found to be mostly dissolved without any additional ocular complications. PMID:27999699

  9. Characteristic analysis on susceptibility weighted imaging of intravitreous foreign body of autologous eyelashes in rabbits.

    PubMed

    Yang, Yun-jun; Cheng, Jing-liang; Wang, Juan; Zhang, Yong; Li, Hua-li

    2010-10-01

    To explore the characteristics of susceptibility weighted imaging (SWI) of the intravitreous foreign body of autologous eyelashes in rabbits. A total of 12 New Zealand white rabbits, either sex, weighing 2.5-3.5 kg, and provided by the Experimental Animal Center of Henan Province were employed in this study. For each rabbit, 5 autologous eyelashes (1 cm in length and 0.2-0.3 mm in diameter) were implanted into the right ocular vitreum, while the left control ocular vitreum received sham operation but nothing was implanted. SWI sequential test was made 2 hours postoperatively. Then the rabbits were killed and the specimens of the vitreous bodies of the rabbits were obtained. Hematoxylin and eosin staining and histological examinations were performed. The autologous eyelashes in 8 ocular vitreums of rabbits showed linear low signal intensity on the magnitude images and susceptibility weighted images, but linear high signal intensity on the phase images. Among the 12 experimental rabbits, 5 eyelashes in the right vitreum were completely shown in 3 rabbits, partly shown in 5 rabbits (2 eyelashes shown in 3 rabbits and 3 eyelashes shown in 2 rabbits), and not shown in 4 rabbits. SWI of the foreign body of intravitreous autologous eyelashes in rabbits has its own characteristics. The combined application of SWI sequential magnitude images, susceptibility weighted images and phase images is helpful to the detection and diagnosis of intravitreous autologous eyelashes in rabbits.

  10. [The results of intravitreal bevacizumab in subretinal neovascularisation in angioid streaks].

    PubMed

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    To assess the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization (CNV) due to angioid streaks; To assess the safety and results stability; Prospective, nonrandomized, interventional case study on choroidal neovascularization due to angioid streaks treated with intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. 8 cases with CNV associated to angioid streaks were evaluated between January 2007 and January 2013. Mean age of patients in the study was 52,36 +/- 4,33 years (ranging 42-64 years). The mean number of intravitreal injections was 4.64 +/- 0,42 (ranging between 3-8 injections). Mean visual acuity improved significantly in all cases after 3 intravitreal injections with a gain of more than 15 letters in 6 out of 8 cases (75%). OCT confirmed reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the CNV reoccurred in 5 out of 8 cases (62.5%) requiring additional treatment. 3 out of 8 cases finally lost more than 5 letters due to subretinal fibrosis. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the CNV due to angioid streaks. High recurrence rate and quick lesion progression to subretinal fibrosis might be responsible for long-term poor functional results in this type of CNVs. More cases are needed for validation.

  11. Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study.

    PubMed

    Francis, Jasmine H; Schaiquevich, Paula; Buitrago, Emiliano; Del Sole, María José; Zapata, Gustavo; Croxatto, J Oscar; Marr, Brian P; Brodie, Scott E; Berra, Alejandro; Chantada, Guillermo L; Abramson, David H

    2014-09-01

    Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model. Clinical and preclinical, prospective, cohort study. In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 μg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 μg of intravitreal melphalan or vehicle to the right eye. Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated. For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings. By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 μV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b

  12. [Intravitreal ranibizumab therapy for choroidal neovascularization secondary to pathological myopia].

    PubMed

    Lukács, Regina; Sándor, Gábor; Resch, Miklós; Szabó, Antal; Barcsay, György; Ecsedy, Mónika; Szepessy, Zsuzsanna; Nagy, Zoltán Zsolt; Papp, András

    2017-04-01

    Pathological myopia is one of the leading causes of vision loss worldwide, especially among young people of working age. Choroidal neovascularization is one of the most important cause of visual impairment in pathological myopia. To evaluate the efficacy of intravitreal ranibizumab for the treatment of myopic choroidal neovascularization. In this retrospective analysis 14 eyes of 14 patients (mean age: 61 ± 17 years) with myopic choroidal neovascularization were treated with intravitreal ranibizumab as needed. Best-corrected visual acuity, thickness of choroidal neovascularization lesion and the number of injections were assessed. The mean visual acuity changed from 55.8 ± 19.3 letters to 64.8 + 15.5 at 12 months (p = 0.0414), and 62.6 ± 16.3 during follow-up time (p = 0.2896). Mean follow-up time was 19.7 ± 23.9 months, average number of injections was 2.8 ± 2.1. Visual acuity declined in four patients despite the treatment. Intravitreal ranibizumab is an effective therapy in pathological myopia. Some patients experience deterioration of visual acuity despite of treatment. Orv. Hetil., 2017, 158(15), 579-586.

  13. Short-term efficacy of intravitreal dobesilate in central serous chorioretinopathy

    PubMed Central

    2012-01-01

    Purpose To report the anatomic and functional outcome of intravitreal dobesilate to treat recurrent central serous chorioretinopathy (CSC). Methods This is an interventional case report in which dobesilate was intravitreally injected in a case of recurrent CSC. Main measures included fundoscopy, Snellen visual acuity (VA) testing, fluorescein angiography and optical coherence tomography (OCT). Results We present anatomical and functional evidences, obtained as early as eleven days after the treatment, of the efficacy of intravitreal dobesilate, in the treatment of chronic CSC condition. The effect after intravitreal dobesilate injection for CSC might be related to the normalization of retinal architecture. Conclusions Intravitreal dobesilate may be an effective treatment option for recurrent CSC. PMID:22788836

  14. Retinal pseudoangiitis after intravitreal triamcinolone

    PubMed Central

    García-Campos, Jose Manuel; García-Basterra, Ignacio; Kamal-Salah, Radua; Baquero-Aranda, Isabel

    2015-01-01

    We present a case of a 40-year-old woman with a fundus image similar to frosted retinal angiitis after undergoing pars plana vitrectomy and intravitreal triamcinolone injection. The patient with diabetic retinopathy was referred to our hospital with vision loss in her right eye secondary to vitreous haemorrhage. After pars plana vitrectomy and injection of triamcinolone acetonide a funduscopy examination revealed deposits of triamcinolone along the retinal vessels simulating a frosted retinal angiitis. Triamcinolone deposits along blood vessels could be the result of the reabsorption process of these crystals by the perivascular macrophages. Further studies are needed. PMID:25678611

  15. Rescue of retinal degeneration by intravitreally injected adult bone marrow–derived lineage-negative hematopoietic stem cells

    PubMed Central

    Otani, Atsushi; Dorrell, Michael Ian; Kinder, Karen; Moreno, Stacey K.; Nusinowitz, Steven; Banin, Eyal; Heckenlively, John; Friedlander, Martin

    2004-01-01

    Inherited retinal degenerations afflict 1 in 3,500 individuals and are a heterogeneous group of diseases that result in profound vision loss, usually the result of retinal neuronal apoptosis. Atrophic changes in the retinal vasculature are also observed in many of these degenerations. While it is thought that this atrophy is secondary to diminished metabolic demand in the face of retinal degeneration, the precise relationship between the retinal neuronal and vascular degeneration is not clear. In this study we demonstrate that whenever a fraction of mouse or human adult bone marrow–derived stem cells (lineage-negative hematopoietic stem cells [Lin– HSCs]) containing endothelial precursors stabilizes and rescues retinal blood vessels that would ordinarily completely degenerate, a dramatic neurotrophic rescue effect is also observed. Retinal nuclear layers are preserved in 2 mouse models of retinal degeneration, rd1 and rd10, and detectable, albeit severely abnormal, electroretinogram recordings are observed in rescued mice at times when they are never observed in control-treated or untreated eyes. The normal mouse retina consists predominantly of rods, but the rescued cells after treatment with Lin– HSCs are nearly all cones. Microarray analysis of rescued retinas demonstrates significant upregulation of many antiapoptotic genes, including small heat shock proteins and transcription factors. These results suggest a new paradigm for thinking about the relationship between vasculature and associated retinal neuronal tissue as well as a potential treatment for delaying the progression of vision loss associated with retinal degeneration regardless of the underlying genetic defect. PMID:15372100

  16. Pharmacokinetics and safety of intravitreal caspofungin.

    PubMed

    Shen, Ying-Cheng; Liang, Chiao-Ying; Wang, Chun-Yuan; Lin, Keng-Hung; Hsu, Min-Yen; Yuen, Hon-Leung; Wei, Li-Chen

    2014-12-01

    Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 μg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 μg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 μg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.

  17. Successful treatment of pseudophakic cystoid macular edema with intravitreal bevacizumab.

    PubMed

    Barone, Antonio; Prascina, Francesco; Russo, Vincenzo; Iaculli, Cristiana; Primavera, Vito; Querques, Giuseppe; Stella, Andrea; Delle Noci, Nicola

    2008-07-01

    A 67-year-old woman developed refractory pseudophakic cystoid macular edema (CME) after uneventful phacoemulsification. Three months after an intravitreal injection of bevacizumab (1.25 mg), the CME was completely resolved, with resultant improvement in visual acuity.

  18. Miniaturized flow injection analysis system

    DOEpatents

    Folta, J.A.

    1997-07-01

    A chemical analysis technique known as flow injection analysis is described, wherein small quantities of chemical reagents and sample are intermixed and reacted within a capillary flow system and the reaction products are detected optically, electrochemically, or by other means. A highly miniaturized version of a flow injection analysis system has been fabricated utilizing microfabrication techniques common to the microelectronics industry. The microflow system uses flow capillaries formed by etching microchannels in a silicon or glass wafer followed by bonding to another wafer, commercially available microvalves bonded directly to the microflow channels, and an optical absorption detector cell formed near the capillary outlet, with light being both delivered and collected with fiber optics. The microflow system is designed mainly for analysis of liquids and currently measures 38{times}25{times}3 mm, but can be designed for gas analysis and be substantially smaller in construction. 9 figs.

  19. Miniaturized flow injection analysis system

    DOEpatents

    Folta, James A.

    1997-01-01

    A chemical analysis technique known as flow injection analysis, wherein small quantities of chemical reagents and sample are intermixed and reacted within a capillary flow system and the reaction products are detected optically, electrochemically, or by other means. A highly miniaturized version of a flow injection analysis system has been fabricated utilizing microfabrication techniques common to the microelectronics industry. The microflow system uses flow capillaries formed by etching microchannels in a silicon or glass wafer followed by bonding to another wafer, commercially available microvalves bonded directly to the microflow channels, and an optical absorption detector cell formed near the capillary outlet, with light being both delivered and collected with fiber optics. The microflow system is designed mainly for analysis of liquids and currently measures 38.times.25.times.3 mm, but can be designed for gas analysis and be substantially smaller in construction.

  20. Macular ischemia after intravitreal amikacin on patient with intraocular foreign body

    PubMed Central

    Kartasasmita, Arief; Mona, Susi; Iskandar, Erwin; Sovani, Iwan; Panggabean, Djonggi

    2017-01-01

    Background: Although still used in third world countries, amikacin has a harmful effect to be used intravitreally. Purpose: To report macular ischemia after an intravitreal injection of amikacin Methods: A case report regarding a traumatized eye of a 26-year-old man that was injected intravitreally with amikacin due to intraocular foreign body endophthalmitis Results: Angiography and OCT show macular ischemia due to amikacin toxicity. Conclusion: The case reported here is to alert about the potential harmful effect of intravitreally injected amikacin despite its role as an accepted regimen for endohthalmitis cases. PMID:28401030

  1. Macular ischemia after intravitreal amikacin on patient with intraocular foreign body.

    PubMed

    Kartasasmita, Arief; Mona, Susi; Iskandar, Erwin; Sovani, Iwan; Panggabean, Djonggi

    2017-01-01

    Background: Although still used in third world countries, amikacin has a harmful effect to be used intravitreally. Purpose: To report macular ischemia after an intravitreal injection of amikacin Methods: A case report regarding a traumatized eye of a 26-year-old man that was injected intravitreally with amikacin due to intraocular foreign body endophthalmitis Results: Angiography and OCT show macular ischemia due to amikacin toxicity. Conclusion: The case reported here is to alert about the potential harmful effect of intravitreally injected amikacin despite its role as an accepted regimen for endohthalmitis cases.

  2. Gene therapy following subretinal AAV5 vector delivery is not affected by a previous intravitreal AAV5 vector administration in the partner eye

    PubMed Central

    Li, Wensheng; Kong, Fansheng; Li, Xia; Dai, Xufeng; Liu, Xiaoqiang; Zheng, Qinxiang; Wu, Ronghan; Zhou, Xiangtian; Lü, Fan; Chang, Bo; Li, Qiuhong; Hauswirth, William W.; Pang, Ji-jing

    2009-01-01

    Purpose In an earlier study we found normal adeno-associated viral vector type 2 (AAV2)-mediated GFP expression after intravitreal injection to one eye of normal C57BL/6J mice. However, GFP expression was very poor in the partner eye of the same mouse if this eye received an intravitreal injection of the same vector one month after the initial intravitreal injection. We also found both injections worked well if they were subretinal. In this study, we tested whether the efficiency of subretinal AAV vector transduction is altered by a previous intravitreal injection in the partner eye and more importantly whether therapeutic efficiency is altered in the rd12 mouse (with a recessive RPE65 mutation) after the same injection series. Methods One μl of scAAV5-smCBA-GFP (1x1013 genome containing viral particles per ml) was intravitreally injected into the right eyes of four-week-old C57BL/6J mice and 1 μl of scAAV5-smCBA-hRPE65 (1x1013 genome containing viral particles per ml) was intravitreally injected into the right eyes of four-week-old rd12 mice Four weeks later, the same vectors were subretinally injected into the left eyes of the same C57BL/6J and rd12 mice. Left eyes of another cohort of eight-week-old rd12 mice received a single subretinal injection of the same scAAV5-smCBA-hRPE65 vector as the positive control. Dark-adapted electroretinograms (ERGs) were recorded five months after the subretinal injections. AAV-mediated GFP expression in C57BL/6J mice and RPE65 expression and ERG restoration in rd12 mice were evaluated five months after the second subretinal injection. Frozen section analysis was performed for GFP fluorescence in C57BL/6J mice and immunostaining for RPE65 in rd12 eyes. Results In rd12 mice, dark-adapted ERGs were minimal following the first intravitreal injection of scAAV5-smCBA-RPE65. Following subsequent subretinal injection in the partner eye, dramatic ERG restoration was recorded in that eye. In fact, ERG b-wave amplitudes were

  3. Diabetic papillopathy treated with intravitreal ranibizumab

    PubMed Central

    Yildirim, Mine; Kilic, Deniz; Dursun, Mehmet Emin; Dursun, Birgul

    2017-01-01

    In this report, we present a case of diabetic papillopathy that resolved after a single dose of intravitreal ranibizumab injection. A 50-year-old male presented with painless visual loss in his right eye. His visual acuity was 1/10 in the right eye and 10/10 in the left eye. Anterior segment examination of both eyes was unremarkable. Posterior segment of the right eye showed nonproliferative diabetic retinopathy with a swollen optic disc. Fluorescein angiography and optical coherence tomography were performed. There was dye leakage from the right optic disc. Optical coherence tomography revealed a significant increase in retinal nerve fiber layer thickness. Magnetic resonance imaging of the brain and orbit were normal. The patient received a single intravitreal ranibizumab (0.5 mg) injection. Two weeks after the injection, there was a marked regression of the disc swelling. Three months after the injection the optic disc was pallor and visual acuity was 6/10. PMID:28356776

  4. Tower microneedle via reverse drawing lithography for innocuous intravitreal drug delivery.

    PubMed

    Lee, Chang Yeol; Lee, Kwang; You, Yong Sung; Lee, Sung Ho; Jung, Hyungil

    2013-06-01

    The "tower microneedle" (TM) via reverse drawing lithography for intravitreal injection by fabricating a long hollow microneedle on the blunt hypodermic needle: The hollow hole between the microneedle and hypodermic needle is aligned concentrically, and fifteen degree bevel angle is introduced to TM by laser cutting to achieve intravitreal injection with minimal damage to eye tissue.

  5. A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab) intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

    PubMed Central

    Patel, Praveen J; Bunce, Catey; Tufail, Adnan

    2008-01-01

    Background The management of neovascular age-related macular degeneration (nAMD) has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents). One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication) despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab) for choroidal neovascularisation (ABC) trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment). Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a) defining the control group (b) use of gain in vision as primary efficacy end-point and (c) use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled trials ISRCTN

  6. Clinical outcomes of primary intraocular lymphoma patients treated with front-line systemic high-dose methotrexate and intravitreal methotrexate injection.

    PubMed

    Ma, Wei-Li; Hou, Hsin-An; Hsu, Ya-Jui; Chen, Yin-Kai; Tang, Jih-Luh; Tsay, Woei; Yeh, Po-Ting; Yang, Chung-May; Lin, Chang-Ping; Tien, Hwei-Fang

    2016-03-01

    A standard treatment for patients with primary intraocular lymphoma (PIOL) remains unclear. This study retrospectively analyzed the clinical features and outcomes of 19 patients with PIOL who were treated with a first-line therapy comprising combined intravenous high-dose methotrexate and intravitreal methotrexate between January 2003 and December 2013. Thirteen (68.4 %) patients were female, and the median age at diagnosis was 57 (39-77 years). Diagnoses were based on the identification of abnormal lymphoid cells in vitreous fluid. Ten (52.6 %) patients had bilateral eye involvement, and six had concurrent central nervous system (CNS) involvement. All 19 patients achieved complete remission (CR) as confirmed by cytological examination of vitreous and cerebrospinal fluid and brain imaging if CNS was involved. Patients with concurrent brain involvement required a longer time to achieve CR. However, the duration of complete remission did not differ between patients with and without CNS involvement. The 5-year overall survival rate was 55.8 % for the total cohort and was higher (68.8 %) in patients with isolated PIOL than in those with concurrent CNS involvement. In all patients, methotrexate treatment was well tolerated, with manageable side effects. We conclude that combined intravitreal methotrexate and systemic high-dose methotrexate treatment is effective in patients with PIOL.

  7. A Phase 2 Randomized Clinical Trial of Intravitreal Bevacizumab for Diabetic Macular Edema

    PubMed Central

    2008-01-01

    Objective To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME). Design Randomized phase 2 clinical trial. Participants 121 eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32-20/320. Interventions Random assignment to one of five groups: focal photocoagulation at baseline (N=19, Group A), intravitreal injection of 1.25mg bevacizumab at baseline and 6 weeks (N=22, Group B), intravitreal injection of 2.5mg bevacizumab at baseline and 6 weeks (N=24, Group C), intravitreal injection of 1.25mg bevacizumab at baseline and sham injection at 6 weeks (N=22, Group D), or intravitreal injection of 1.25mg bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (N=22, Group E). Main Outcome Measures Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. Results At baseline, median CST was 411 microns and median Snellen VA equivalent was 20/50. Compared with Group A, Groups B and C had a greater reduction in CST at 3 weeks and about one line better median visual acuity over 12 weeks. There were no meaningful differences between Groups B and C in CST reduction or VA improvement. A CST reduction >11% (the reliability limit) was present at 3 weeks in 36/84 (43%) bevacizumab-treated eyes and in 5/18 (28%) eyes treated with laser alone, and at 6 weeks in 31/84 (37%) and 9/18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in one eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (N=2), congestive heart failure (N=1), elevated blood pressure (N=3), and worsened renal function (N=3). Conclusion These results demonstrate that

  8. Long-term results of intravitreal ranibizumab for the treatment of retinal angiomatous proliferation and utility of an advanced RPE analysis performed using spectral-domain optical coherence tomography.

    PubMed

    Inoue, Maiko; Arakawa, Akira; Yamane, Shin; Kadonosono, Kazuaki

    2014-07-01

    To report the results of 3-year follow-up examinations after intravitreal ranibizumab (IVR) injection for the treatment of retinal angiomatous proliferation (RAP) and to examine the utility of an advanced retinal pigment epithelium (RPE) analysis performed using spectral-domain optical coherence tomography (SD-OCT). We retrospectively reviewed 17 treatment-naïve eyes in 14 patients (4 men, 10 women; age range 71-87 years; mean age 80 years) treated with IVR. All the patients received three consecutive monthly injections of 0.5 mg/0.05 mL of ranibizumab as an induction treatment. Retreatment was allowed if evidence of clinical deterioration was noted or if an SD-OCT examination performed at a 1-month follow-up showed intraretinal oedema, subretinal fluid, or recurrent pigment epithelial detachment. The primary outcome measures were best-corrected visual acuity (BCVA) and central foveal thickness (CFT) as evaluated using SD-OCT. Furthermore, we investigated the atrophic area at 36 months using advanced RPE analysis provided by SD-OCT and analysed the correlation with the BCVA. The mean BCVA was well maintained from 0.57 at baseline to 0.52 at 36 months (p=0.219). The CFT decreased significantly from 317 to 223 µm at 36 months (p<0.001). The mean number of injections was 10.2. Sixteen of the 17 patients (94.1%) showed recurrence during the maintenance phase. Better visual acuity at 36 months was also associated with better visual acuity at baseline and absence of macular atrophy (MA) identified with advanced RPE analysis at 36 months (p<0.001, p=0.012, respectively). The intravitreal injection of ranibizumab was effective for stabilising vision in patients with RAP, as evaluated at a 3-year follow-up examination. Advanced RPE analysis is useful for investigating atrophic areas after IVR. Visual acuity at baseline and progression of MA might be important for BCVA after IVR. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  9. Ex vivo investigation of ocular tissue distribution following intravitreal administration of connexin43 mimetic peptide using the microdialysis technique and LC-MS/MS.

    PubMed

    Bisht, Rohit; Mandal, Abhirup; Rupenthal, Ilva D; Mitra, Ashim K

    2016-12-01

    This study aimed to develop and evaluate an ex vivo eye model for intravitreal drug sampling and tissue distribution of connexin43 mimetic peptide (Cx43MP) following intravitreal injection using the microdialysis technique and LC-MS/MS. An LC-MS/MS method was developed, validated, and applied for quantification of Cx43MP in ocular tissues. Microdialysis probes were calibrated for in vitro recovery studies. Bovine eyes were fixed in a customized eye holder and after intravitreal injection of Cx43MP, microdialysis probes were implanted in the vitreous body. Vitreous samples were collected at particular time intervals over 24 h. Moreover, 24 and 48 h after intravitreal injection ocular tissues were collected, processed, and analyzed for Cx43MP concentrations using LC-MS/MS. The LC-MS/MS method showed good linearity (r (2) = 0.9991). The mean percent recovery for lower (LQC), medium (MQC), and higher quality control (HQC) (0.244, 3.906, and 125 μg/mL) was found to be 83.83, 84.92, and 94.52, respectively, with accuracy ranges between 96 and 99 % and limits of detection (LOD) and quantification (LOQ) of 0.122 and 0.412 μg/mL. The in vitro recovery of the probes was found to be over 80 %. As per microdialysis sample analysis, the Cx43MP concentration was found to increase slowly in the vitreous body up to 16 h and thereafter declined. After 48 h, the Cx43MP concentration was higher in vitreous, cornea, and retina compared to lens, iris, and aqueous humor. This ex vivo model may therefore be a useful tool to investigate intravitreal kinetics and ocular disposition of therapeutic molecules after intravitreal injection.

  10. Intravitreal bevacizumab for pediatric exudative retinal diseases.

    PubMed

    Salman, Abdelrahman G

    2011-04-01

    To detect if intravitreal bevacizumab can reduce retinal exudation, improve visual and anatomical outcomes, and facilitate the treatment in various pediatric exudative retinal diseases. Prospective, non-randomized, case series of nine eyes of pediatric exudative retinal diseases less than 18 years old which included six eyes with juvenile diabetic retinopathy, two eyes in children with Coats' disease, and one eye with myopic choroidal neovascular membrane (CNV). All eyes received only intravitreal bevacizumab injection 1.25 mg/0.05 ml as the primary treatment. The need for adjuvant ablative procedures, including laser photocoagulation or cryotherapy, were performed and recorded. The need for supplementary intravitreal bevacizumab injection was recorded. The changes in pre- and post-operative best-corrected visual acuity (BCVA) and central macular thickness (CMT) were recorded. Serial optical coherent tomography (OCT) and fundus flourescein angiography (FFA) were performed to follow treatment efficacy. The study included 19 eyes of 11 patients with age equal to or less than eighteen years with exudative retinal diseases including type I DM (n = sixteen eyes), Coats' disease (n = 2 eyes), and due to myopic CNV (n = 1 eye). Mean pre-injection log MAR for all was 0.605 ± 0.174 and mean post-injection for all log MAR was 0.284 ± 0.247. While Mean pre-injection log MAR for DR and myopic CNV patients was 0.576 + 0.152 SD and mean post-injection log MAR for DR and myopic CNV patients was 0.229 + 0.189 at one year. Serial OCT measurements showed that mean CMT for all eyes was 355.8 ± 35.3 μm SD at baseline, which was decreased to 222.42 + 26.2 μm SD. The two eyes of Coats' disease needed another two supplementary intravitreal bevacizumab injections. No ocular or systemic complications related to bevacizumab were noted during the entire course of follow-up. Intravitreal bevacizumab appears to be a well-tolerated treatment for pediatric age group

  11. Ocular trace metal kinetics and toxicology. I. The distribution of intravitreally injected 67Cu++ within intraocular compartments and its loss from the globe

    SciTech Connect

    Bito, L.Z.; Baroody, R.A.

    1987-01-01

    Radioactive copper (67Cu++) was injected into the center of the vitreous body of rabbits. The relatively rapid initial loss of 67Cu from the vitreous was associated with its accumulation in intraocular tissues. At 24 hr, 20% of the injected 67Cu was found in the retina, representing the highest 67Cu concentration among all ocular tissues, and this high 67Cu concentration was maintained in this tissue throughout the 10-day observation period. Significant amounts of 67Cu were not detected in the aqueous humor at any time. About one-half of the injected 67Cu was lost from the whole globe in 5 days, but the remaining Cu was retained in the globe during the next 5 days. Eyes that received a large dose of CuSO4 in addition to the tracer showed decreased 67Cu activity in the retina and a slight increase in the aqueous humor. Endotoxin-induced ocular inflammation decreased the rate of 67Cu loss from the vitreous, reduced its accumulation by the retina, and increased 67Cu entry into the aqueous humor. It is concluded that 67Cu is retained in the vitreous and the globe due to its binding by, and/or uptake into, intraocular tissues, especially the retina. Cu does not effectively enter the anterior chamber from the vitreous, apparently due to its effective removal by the ciliary processes, thus ruling out the possibility of identifying the existence of Cu-containing intraocular foreign bodies in the posterior segment of the eye by analysis of Cu in the aqueous humor.

  12. Factors correlated with the resolution of macular oedema after one dose injection of intravitreal triamcinolone acetonide treatment in branch retinal vein occlusion.

    PubMed

    Zhang, Shuang; An, Ningyu; Ha, Wenjing; Zhang, Shaochi; Hu, Xiaowen; Ma, Aihua; Zhao, Bojun

    2016-06-01

    To investigate the predictive baseline factors for a successful outcome following one dose of intravitreal triamcinolone acetonide (IVTA) in patients with macular oedema (ME) caused by branch retinal vein occlusion (BRVO). This retrospective study enrolled patients with ME (macular retinal thickness [MRT] ≥ 300 µm) due to BRVO who still had ME 3 months after grid laser photocoagulation. Patients were divided according to treatment into an IVTA group and a laser-only group. The resolution of ME was documented at months 3 and 6. A total of 154 eyes with ME were investigated: IVTA group (90 eyes) and laser-only group (64 eyes). Predictive factors for successful IVTA treatment were younger age, shorter duration of ME, initial onset ME, accompanied by serous retinal detachment, few concomitant systemic diseases and nonischaemic BRVO. A broken foveal capillary ring was related to a poor treatment outcome. Eyes with cystoid spaces in the outer plexiform layer were more likely to have a good treatment response. IVTA is effective for resolving ME due to BRVO after grid laser photocoagulation treatment. © The Author(s) 2016.

  13. Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Akkoç, Tolga; Eraslan, Muhsin; Şahin, Özlem; Özkara, Selvinaz; Vardar Aker, Fugen; Subaşı, Cansu; Karaöz, Erdal; Akkoç, Tunç

    2016-01-01

    Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function. PMID:27300133

  14. Dexamethasone intravitreal implant in the treatment of diabetic macular edema

    PubMed Central

    Dugel, Pravin U; Bandello, Francesco; Loewenstein, Anat

    2015-01-01

    Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reaction, and is characterized by blood–retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg) administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation ≥25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (<2

  15. Intravitreal Melphalan for Vitreous Seeds: Initial Experience in China

    PubMed Central

    Ji, Xunda; Hua, Peiyan; Li, Jing; Li, Jiakai; Zhao, Junyang; Zhao, Peiquan

    2016-01-01

    Purpose. To evaluate the efficacy of intravitreal melphalan for vitreous seeds from retinoblastoma in Chinese patients. Methods. This is a retrospective review of 17 consecutive Chinese patients (19 eyes) with viable vitreous seeds from retinoblastoma. The patients received multiple intravitreal injections of 20 ug melphalan. Results. The International Classification of Retinoblastoma groups were B in 1 eye, C in 5 eyes, D in 11 eyes, and E in 2 eyes. On average, 6 injections (range: 1–15) were given to each eye at the interval of 2–4 weeks. Successful control of vitreous seeds was achieved in 16 of 19 eyes (84.21%). Globe retention was achieved in 73.68% (14/19) eyes. The patients were followed up for 27 months on average (median: 26; range: 17–42 months). There is a significant difference in response to intravitreal melphalan for cloud, spheres, and dust seeds with a median number of injections of 9, 6, and 3, respectively (P = 0.003). Complications related to intravitreal melphalan included vitreous hemorrhage, cataract, salt-and-pepper retinopathy, and pupil posterior synechia. There was no case of epibulbar extension or systemic metastasis within the period of follow-up. Conclusion. Intravitreal melphalan achieved a high local control rate for vitreous seeds without extraocular extension and with acceptable toxicity in Chinese retinoblastoma patients. PMID:26977313

  16. Intravitreal infusion: A novel approach for intraocular drug delivery

    PubMed Central

    Tian, Jiao; Liu, Jia; Liu, Xiao; Xiao, Yangyan; Tang, Luosheng

    2016-01-01

    Intraocular injection has become an increasingly important intervention in the treatment of posterior segment diseases. However, an acute intraocular pressure (IOP) elevation after intravitreal injection is a common concern. This study aimed to evaluate the efficacy of intravitreal infusion in maintaining stable IOP in a rabbit model. Trypan blue (TB) 0.06% with an external pump was used to evaluate intravitreal infusion in rabbit eyes. Groups A (50 μL), B (100 μL), C (150 μL), and D (200 μL) were slowly infused over 30 minutes with TB. As a control, Group E underwent conventional intravitreal injection of 100 μL of TB. Group F received a bolus infusion of 100 μL of TB within 1 minute. The mean increases in IOP during infusion for each group were: Group A (7.93 ± 3.80 mmHg), B (13.97 ± 3.17 mmHg), C (19.91 ± 6.06 mmHg) and D (29.38 ± 8.97 mmHg). Immediately post-injection in group E the mean increase in IOP amounted to 34.33 ± 6.57 mmHg. The mean increase in IOP of group F after bolus infusion was 49.89 ± 1.71 mmHg. Intravitreal infusion maintains a stable IOP and provides a controlled infusion speed compared with intravitreal injection. PMID:27886224

  17. Functional and anatomical results after a single intravitreal Ozurdex injection in retinal vein occlusion: a 6-month follow-up -- the SOLO study.

    PubMed

    Bezatis, Athanasios; Spital, Georg; Höhn, Fabian; Maier, Mathias; Clemens, Christoph R; Wachtlin, Joachim; Lehmann, Florian; Hattenbach, Lars Olof; Feltgen, Nicolas; Meyer, Carsten H

    2013-08-01

    To evaluate the efficacy of intravitreal dexamethasone implants in eyes with cystoid macular oedema (CME) secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) in the clinical everyday practice, examine the effects of early retreatment and compare the results with the GENEVA study. The charts of 102 patients (102 eyes) with CME secondary to BRVO (n = 54) or CRVO (n = 48) treated with Ozurdex at 8 centres were retrospectively reviewed. The patients were examined monthly over a 24-week period. Slit-lamp biomicroscopy, measurement of best-corrected visual acuity (BCVA) and measurement of the central retinal thickness (CRT) with spectral-domain optical coherence tomography (SD-OCT) were performed at baseline and at every follow-up examination. With progression of the disease (loss of one line or increased central retinal thickness (CRT) of 150 μm), a reinjection of Ozurdex or anti-VEGF was offered. Additional supplementing sectorial or panretinal laser photocoagulation was considered based on the individual status of the retina. In the BRVO group, the median BCVA was 0.6 logMAR (Snellen equivalent of 0.25) at baseline and improved to 0.4 logMAR (Snellen equivalent of 0.40) after 4 weeks, 0.3 logMAR (Snellen equivalent of 0.50) after 8 weeks, 0.4 logMAR (Snellen equivalent of 0.40) after 12 weeks, 0.5 logMAR (Snellen equivalent of 0.32) after 16 weeks, 0.4 logMAR (Snellen equivalent of 0.40) after 20 weeks and 0.45 logMAR (Snellen equivalent of 0.35) after 24 weeks. The mean CRT was 559 ± (SD) 209 μm at baseline and it decreased to 335 ± 148 μm after 4 weeks, 316 ± 137 μm after 8 weeks, 369 ± 126 μm after 12 weeks, 407 ± 161 μm after 16 weeks, 399 ± 191 μm after 20 weeks and 419 ± 196 μm after 24 weeks. In the CRVO group, the median BCVA was 0.7 logMAR (Snellen equivalent of 0.20) at baseline and improved to 0.4 logMAR (Snellen equivalent of 0.40) after 4 weeks, 0.4 logMAR (Snellen equivalent of 0.40) after 8 weeks, 0

  18. Analysis of rocket engine injection combustion processes

    NASA Technical Reports Server (NTRS)

    Salmon, J. W.; Saltzman, D. H.

    1977-01-01

    Mixing methodology improvement for the JANNAF DER and CICM injection/combustion analysis computer programs was accomplished. ZOM plane prediction model development was improved for installation into the new standardized DER computer program. An intra-element mixing model developing approach was recommended for gas/liquid coaxial injection elements for possible future incorporation into the CICM computer program.

  19. Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates.

    PubMed

    Kotterman, M A; Yin, L; Strazzeri, J M; Flannery, J G; Merigan, W H; Schaffer, D V

    2015-02-01

    Gene delivery vectors based on adeno-associated viruses (AAV) have exhibited promise in both preclinical disease models and human clinical trials for numerous disease targets, including the retinal degenerative disorders Leber's congenital amaurosis and choroideremia. One general challenge for AAV is that preexisting immunity, as well as subsequent development of immunity following vector administration, can severely inhibit systemic AAV vector gene delivery. However, the role of neutralizing antibodies (NABs) in AAV transduction of tissues considered to be immune privileged, such as the eye, is unclear in large animals. Intravitreal AAV administration allows for broad retinal delivery, but is more susceptible to interactions with the immune system than subretinal administration. To assess the effects of systemic anti-AAV antibody levels on intravitreal gene delivery, we quantified the anti-AAV antibodies present in sera from non-human primates before and after intravitreal injections with various AAV capsids. Analysis showed that intravitreal administration resulted in an increase in anti-AAV antibodies regardless of the capsid serotype, transgene or dosage of virus injected. For monkeys injected with wild-type AAV2 and/or an AAV2 mutant, the variable that most significantly affected the production of anti-AAV2 antibodies was the amount of virus delivered. In addition, post-injection antibody titers were highest against the serotype administered, but the antibodies were also cross-reactive against other AAV serotypes. Furthermore, NAB levels in serum correlated with those in vitreal fluid, demonstrating both that this route of administration exposes AAV capsid epitopes to the adaptive immune system and that serum measurements are predictive of vitreous fluid NAB titers. Moreover, the presence of preexisting NAB titers in the serum of monkeys correlated strongly (R=0.76) with weak, decaying or no transgene expression following intravitreal administration of AAV

  20. TOWARDS A TREATMENT FOR DIABETIC RETINOPATHY: Intravitreal Toxicity and Preclinical Safety Evaluation of Inducible Nitric Oxide Synthase Inhibitors.

    PubMed

    Carr, B Cameron; Emigh, Caitlyn E; Bennett, Lea D; Pansick, Andrew D; Birch, David G; Nguyen, Chan

    2017-01-01

    The purpose of this study is to determine the maximum tolerated dose of a single intravitreal injection of aminoguanidine and 1400W, 2 inhibitors of inducible nitric oxide synthase, in rabbit eyes. Inhibition of inducible nitric oxide synthase has already been shown to be beneficial in various animal models of diabetic eye disease. Groups of 4 New Zealand white rabbits were injected with balanced salt solution in the right eye and a single dose of either aminoguanidine (5, 1, 0.25 mg) or 1400W (2 mg and 0.4 mg) in the left eye. Toxicity was assessed by slit-lamp and fundus examination, intraocular pressure and pachymetric measurements, and electrophysiologic and histologic analysis. Eyes injected with high doses of aminoguanidine (5 mg) or 1400W (2 mg) demonstrated severe retinal vascular attenuation and infarction. Lower doses of intravitreal aminoguanidine (1 mg) and 1400W (0.4 mg) caused no significant toxic ocular effects in rabbit eyes. If the difference in vitreal volume between rabbit eyes and human eyes is taken into account, aminoguanidine (2.7 mg) and 1400W (1 mg) would be reasonable intravitreal doses to test for safety and efficacy in early clinical trials.

  1. VOLATILE ORGANIC ANALYSIS BY DIRECT AQUEOUS INJECTION

    EPA Science Inventory

    Gas chromatographic environmental analysis by direct aqueous injection (DAI) was studied for 24 volatile organic analytes (VOAs). Internal standardization was used to determine the precision of analyzing these compounds by DAI. Aequous samples were directly introduced to a gas ch...

  2. Management of macular epiretinal membrane by vitrectomy and intravitreal triamcinolone.

    PubMed

    Shukla, Dhananjay

    2014-04-01

    A patient underwent successful vitrectomy for macular epiretinal membrane with anatomical and functional improvement. 10 weeks later, there was a recurrence of macular edema with corresponding visual decline. An intravitreal injection of triamcinolone acetonide not only restored the macular anatomy but also improved the visual outcome beyond that achieved after surgery.

  3. Release and velocity of micronized dexamethasone implants with an intravitreal drug delivery system: kinematic analysis with a high-speed camera.

    PubMed

    Meyer, Carsten H; Klein, Adrian; Alten, Florian; Liu, Zengping; Stanzel, Boris V; Helb, Hans M; Brinkmann, Christian K

    2012-01-01

    Ozurdex, a novel dexamethasone (DEX) implant, is released by a drug delivery system into the vitreous cavity. We analyzed the mechanical release aperture of the novel applicator, obtained real-time recordings using a high-speed camera system and performed kinematic analysis of the DEX application. Experimental study. : The application of intravitreal DEX implants (6 mm length, 0.46 mm diameter; 700 μg DEX mass, 0.0012 g total implant mass) was recorded by a high-speed camera (500 frames per second) in water (Group A: n = 7) or vitreous (Group B: n = 7) filled tanks. Kinematic analysis calculated the initial muzzle velocity as well as the impact on the retinal surface at approximately 15 mm of the injected drug delivery system implant in both groups. A series of drug delivery system implant positions was obtained and graphically plotted over time. High-speed real-time recordings revealed that the entire movement of the DEX implant lasted between 28 milliseconds and 55 milliseconds in Group A and 1 millisecond and 7 milliseconds in Group B. The implants moved with a mean muzzle velocity of 820 ± 350 mm/s (±SD, range, 326-1,349 mm/s) in Group A and 817 ± 307 mm/s (±SD, range, 373-1,185 mm/s) in Group B. In both groups, the implant gradually decelerated because of drag force. With greater distances, the velocity of the DEX implant decreased exponentially to a complete stop at 13.9 mm to 24.7 mm in Group A and at 6.4 mm to 8.0 mm in Group B. Five DEX implants in Group A reached a total distance of more than 15 mm, and their calculated mean velocity at a retinal impact of 15 mm was 408 ± 145 mm/s (±SD, range, 322-667 mm/s), and the consecutive normalized energy was 0.55 ± 0.44 J/m (±SD). In Group B, none of the DEX implants reached a total distance of 6 mm or more. An accidental application at an angle of 30 grade and consecutively reduced distance of approximately 6 mm may result in a mean velocity of 844 and mean normalized energy of 0.15 J/m (SD ± 0.47) in a

  4. Effect of prior anti-VEGF injections on the risk of retained lens fragments and endophthalmitis post cataract surgery in the elderly

    PubMed Central

    Hahn, Paul; Yashkin, Arseniy P.; Sloan, Frank A.

    2015-01-01

    Objective To investigate the effect of prior intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections on surgical and postoperative complication rates associated with cataract surgery in a nationally representative longitudinal sample of elderly persons. Design Retrospective, longitudinal cohort analysis Participants 203,643 Medicare beneficiaries who underwent cataract surgery from January 1, 2009 to December 31, 2013. Methods Using the 5% sample of Medicare claims data, the study assessed risks of 3 adverse outcomes following receipt of cataract surgery for beneficiaries with a history of prior intravitreal injections. Risks of these outcomes in beneficiaries with a history of intravitreal injections relative to those without were calculated using the Cox proportional hazard model. Main Outcome Measures The primary outcome was the risk of subsequent removal of retained lens fragments within 28 days following cataract surgery. Secondary outcomes were a new diagnosis of acute (<40 days) or delayed onset (40+ days) endophthalmitis as well as risk of a new primary open angle glaucoma diagnosis within 365 days following cataract surgery. Results Prior intravitreal anti-VEGF injections were associated with a significantly increased risk of subsequent retained lens fragment removal within 28 days following cataract surgery (Hazard Ratio (HR): 2.26; 95% Confidence Interval (CI) 1.19–4.30). Prior injections were also associated with increased risk of HR both acute (HR:2.29; 95% CI 1.001 – 5.22) and delayed onset endophthalmitis (HR 3.65; 95% CI 1.65–8.05). Prior injections were not a significant indicator of increased risk of a new primary open angle glaucoma diagnosis. Conclusions A history of intravitreal injections may be a risk factor for cataract surgery-related intraoperative complications and endophthalmitis. Given the frequency of intravitreal injections and cataract surgery, increased preoperative assessment, additional intraoperative

  5. Pharmacokinetics and retinal toxicity of various doses of intravitreal triamcinolone acetonide in rabbits

    PubMed Central

    Ye, You-Fan; Gao, Yong-Feng; Xie, Hua-Tao

    2014-01-01

    Purpose To compare the pharmacokinetics and retinal toxicity of various doses of intravitreal triamcinolone acetonide (TA) in rabbits. Methods The rabbits received intravitreal injections of 4 mg and 8 mg TA. The drug concentrations were determined with high-performance liquid chromatography after extraction from the vitreous at various time points. The main pharmacokinetics parameters were calculated with 3p97 pharmacokinetics software. The intraocular pressure, electroretinography, and pathological examinations were evaluated before and after intravitreal injection of different doses of TA. Results The half-life of intravitreal injection of 4 mg and 8 mg TA was 24 days and 34 days, respectively. No significant differences were found in intraocular pressure (p>0.05) and the electroretinography b-wave amplitudes (p>0.05) among the rabbits before and after intravitreal injection of 4 mg and 8 mg TA. Light and electron microscopy did not show any retinal damage in any group. Conclusions Intravitreal injection of 4 mg and 8 mg TA are safe for the rabbit retina. The injection of 8 mg TA produced a longer vitreous half-life and had a prolonged effect on the retina. This conclusion may be referenced in the clinical application of TA in retinal diseases. PMID:24868137

  6. Intravitreal injection or topical eye-drop application of a μ-calpain C2L domain peptide protects against photoreceptor cell death in Royal College of Surgeons' rats, a model of retinitis pigmentosa.

    PubMed

    Ozaki, Taku; Nakazawa, Mitsuru; Yamashita, Tetsuro; Sorimachi, Hiroyuki; Hata, Shoji; Tomita, Hiroshi; Isago, Hitomi; Baba, Ayaka; Ishiguro, Sei-Ichi

    2012-11-01

    Mitochondrial μ-calpain initiates apoptosis-inducing factor (AIF)-dependent apoptosis in retinal photoreceptor degeneration. Mitochondrial μ-calpain inhibitors may represent therapeutic targets for the disease. Therefore, we sought to identify inhibitors of mitochondrial calpains and determine their effects in Royal College of Surgeons' (RCS) rats, an animal model of retinitis pigmentosa (RP). We synthesized 20-mer peptides of the C2-like (C2L) domain of μ-calpain. Two μ-calpain peptides N2 and N9 inhibited mitochondrial μ-calpain activity (IC(50); 892 and 498nM, respectively), but not other proteases. Western blotting showed that 50μM of both μ-calpain peptides caused specific degradation of mitochondrial μ-calpain. Three-dimensional structure of calpains suggested that the peptides N2 and N9 corresponded to the regions forming salt bridges between the protease core domain 2 and the C2L domain. We determined the inhibitory regions of μ-calpain peptides N2 and N9 using 10-mers, and one peptide, N2-10-2, inhibited the activity of mitochondrial μ-calpain (IC(50); 112nM). We next conjugated the peptide N2-10-2 to the C-terminal of HIV-1 tat (HIV), a cell-penetrating peptide. Using isolated rat liver mitochondria, 50μM HIV-conjugated μ-calpain N2-10-2 peptide (HIV-Nμ, IC(50); 285nM) significantly inhibited AIF truncation. The intravitreal injection of 20mM HIV-Nμ also prevented retinal photoreceptor apoptosis determined by TUNEL staining, and preserved retinal function assessed by electroretinography in RCS rats. Topical application of 40mM HIV-Nμ also prevented apoptosis of retinal photoreceptors in RCS rats. Our results demonstrate that HIV-Nμ, a peptide inhibitor of mitochondrial μ-calpain, offers a new modality for treating RP.

  7. Injection Locking Techniques for Spectrum Analysis

    NASA Astrophysics Data System (ADS)

    Gathma, Timothy D.; Buckwalter, James F.

    2011-04-01

    Wideband spectrum analysis supports future communication systems that reconfigure and adapt to the capacity of the spectral environment. While test equipment manufacturers offer wideband spectrum analyzers with excellent sensitivity and resolution, these spectrum analyzers typically cannot offer acceptable size, weight, and power (SWAP). CMOS integrated circuits offer the potential to fully integrate spectrum analysis capability with analog front-end circuitry and digital signal processing on a single chip. Unfortunately, CMOS lacks high-Q passives and wideband resonator tunability that is necessary for heterodyne implementations of spectrum analyzers. As an alternative to the heterodyne receiver architectures, two nonlinear methods for performing wideband, low-power spectrum analysis are presented. The first method involves injecting the spectrum of interest into an array of injection-locked oscillators. The second method employs the closed loop dynamics of both injection locking and phase locking to independently estimate the injected frequency and power.

  8. Injection Locking Techniques for Spectrum Analysis

    SciTech Connect

    Gathma, Timothy D.; Buckwalter, James F.

    2011-04-19

    Wideband spectrum analysis supports future communication systems that reconfigure and adapt to the capacity of the spectral environment. While test equipment manufacturers offer wideband spectrum analyzers with excellent sensitivity and resolution, these spectrum analyzers typically cannot offer acceptable size, weight, and power (SWAP). CMOS integrated circuits offer the potential to fully integrate spectrum analysis capability with analog front-end circuitry and digital signal processing on a single chip. Unfortunately, CMOS lacks high-Q passives and wideband resonator tunability that is necessary for heterodyne implementations of spectrum analyzers. As an alternative to the heterodyne receiver architectures, two nonlinear methods for performing wideband, low-power spectrum analysis are presented. The first method involves injecting the spectrum of interest into an array of injection-locked oscillators. The second method employs the closed loop dynamics of both injection locking and phase locking to independently estimate the injected frequency and power.

  9. Radiation maculopathy treated with intravitreal bevacizumab.

    PubMed

    Sánchez-Vicente, J L; Muñoz-Morales, A; Galván-Carrasco, M P; Castilla-Lázpita, A; Vital-Berral, C; Alfaro-Juárez, A; Rueda-Rueda, T

    2017-06-01

    A 47 year-old woman with a choroidal melanoma developed a macular oedema secondary to radiation therapy 75 months after brachytherapy plaque. The patient received 3 intravitreal Bevacizumab injections. The patient had a good response to bevacizumab treatment. In fact, there was a reduction in the macular oedema measured by optical coherence tomography (OCT) scan, as well as an improvement in best corrected visual acuity. There was no recurrence of macular oedema, and visual acuity remained stable after 3-years follow-up. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

    PubMed Central

    Orozco-Hernández, Axel; Ortega-Larrocea, Ximena; Sánchez-Bermúdez, Gustavo; García-Aguirre, Gerardo; Cantón, Virgilio Morales; Velez-Montoya, Raul

    2014-01-01

    Background Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were used. Three patients showed a transient elevation of intraocular pressure. Only 50% of the patients regained a visual acuity equal or better to the baseline visual acuity on file. Conclusion The increasing number of intravitreal injections of bevacizumab applied every day, due to its widespread acceptance, might be one reason why the number of cases of sterile endophthalmitis is rising. Fast

  11. Automated Protein Assay Using Flow Injection Analysis

    NASA Astrophysics Data System (ADS)

    Wolfe, Carrie A. C.; Oates, Matthew R.; Hage, David S.

    1998-08-01

    The technique of flow injection analysis (FIA) is a common instrumental method used in detecting a variety of chemical and biological agents. This paper describes an undergraduate laboratory that uses FIA to perform a bicinchoninic acid (BCA) colorimetric assay for quantitating protein samples. The method requires less than 2 min per sample injection and gives a response over a broad range of protein concentrations. This method can be used in instrumental analysis labs to illustrate the principles and use of FIA, or as a means for introducing students to common methods employed in the analysis of biological agents.

  12. SCORE Study Report 7: incidence of intravitreal silicone oil droplets associated with staked-on vs luer cone syringe design.

    PubMed

    Scott, Ingrid U; Oden, Neal L; VanVeldhuisen, Paul C; Ip, Michael S; Blodi, Barbara A; Antoszyk, Andrew N

    2009-11-01

    To evaluate the incidence of intravitreal silicone oil (SO) droplets associated with intravitreal injections using a staked-on vs luer cone syringe design in the SCORE (Standard Care vs COrticosteroid in REtinal Vein Occlusion) Study. Prospective, randomized, phase III clinical trial. The incidence of intravitreal SO was compared among participants exposed to the staked-on syringe design, the luer cone syringe design, or both of the syringe designs in the SCORE Study, which evaluated intravitreal triamcinolone acetonide injection(s) for vision loss secondary to macular edema associated with central or branch retinal vein occlusion. Injections were given at baseline and 4-month intervals, based on treatment assignment and study-defined retreatment criteria. Because intravitreal SO was observed following injections in some participants, investigators were instructed, on September 22, 2006, to look for intravitreal SO at all study visits. On November 1, 2007, the luer cone syringe design replaced the staked-on syringe design. A total of 464 participants received a total of 1,205 injections between November 4, 2004 and February 28, 2009. Intravitreal SO was noted in 141 of 319 participants (44%) exposed only to staked-on syringes, 11 of 87 (13%) exposed to both syringe designs, and 0 of 58 exposed only to luer cone syringes (P < .0001). Among participants with first injections after September 22, 2006, intravitreal SO was noted in 65 of 114 (57%) injected only with staked-on syringes compared with 0 of 58 injected only with luer cone syringes. Differential follow-up is unlikely to explain these results. In the SCORE Study, luer cone syringe design is associated with a lower frequency of intravitreal SO droplet occurrence compared with the staked-on syringe design, likely attributable to increased residual space in the needle hub with the luer cone design.

  13. Intravitreal controlled release of dexamethasone from engineered microparticles of porous silicon dioxide.

    PubMed

    Wang, Chengyun; Hou, Huiyuan; Nan, Kaihui; Sailor, Michael J; Freeman, William R; Cheng, Lingyun

    2014-12-01

    Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterification Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and

  14. Intravitreal Controlled Release of Dexamethasone from Engineered Microparticles of Porous Silicon Dioxide

    PubMed Central

    Wang, Chengyun; Hou, Huiyuan; Nan, Kaihui; Sailor, Michael J; Freeman, William R.; Cheng, Lingyun

    2014-01-01

    Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterificaion Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and

  15. Combined intravitreal bevacizumab and photodynamic therapy for retinal angiomatous proliferation.

    PubMed

    Saito, Masaaki; Shiragami, Chieko; Shiraga, Fumio; Nagayama, Dai; Iida, Tomohiro

    2008-12-01

    To clarify the efficiency of combined therapy with intravitreal bevacizumab injections and photodynamic therapy (PDT) in patients with retinal angiomatous proliferation (RAP). Retrospective, observational, consecutive case series. We retrospectively reviewed 11 consecutive eyes with RAP (10 patients; six men, four women) treated with intravitreal bevacizumab injection and PDT. Patients ranged in age from 63 to 89 years old (average, 79 years). No patients had undergone previous treatment, and patients were followed for at least six months. PDT was applied one or two days after the intravitreal bevacizumab (1.25 mg) injection. The mean best-corrected visual acuity (BCVA) levels at baseline and one, three, and six months after treatment were 0.16, 0.27, 0.31, and 0.29, respectively. A significant improvement in the mean BCVA was observed one, three, and six months after intravitreal bevacizumab injection and PDT (P < .01). The mean improvement in BCVA six months from baseline was 2.64 lines. The BCVA at six months improved in six eyes (54.5%, improved by three lines or more) and was stable in five eyes (45.5%). No patient had a decrease in the BCVA of three or more lines during any six months. The central retinal thickness significantly decreased from 496 +/- 189 microm to 175 +/- 33 microm at six months (P < .001). No patients required retreatment during any six months. No complications such as severe vision loss, endophthalmitis, or systemic events developed. Combined intravitreal bevacizumab and PDT for RAP effectively maintained or improved VA and reduced or eliminated edema in the short-term.

  16. Intravitreal properties of porous silicon photonic crystals

    PubMed Central

    Cheng, L; Anglin, E; Cunin, F; Kim, D; Sailor, M J; Falkenstein, I; Tammewar, A; Freeman, W R

    2009-01-01

    Aim To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery. Methods A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology. Results No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles). Conclusion The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases. PMID:18441177

  17. Analysis of rocket engine injection combustion processes

    NASA Technical Reports Server (NTRS)

    Salmon, J. W.

    1976-01-01

    A critique is given of the JANNAF sub-critical propellant injection/combustion process analysis computer models and application of the models to correlation of well documented hot fire engine data bases. These programs are the distributed energy release (DER) model for conventional liquid propellants injectors and the coaxial injection combustion model (CICM) for gaseous annulus/liquid core coaxial injectors. The critique identifies model inconsistencies while the computer analyses provide quantitative data on predictive accuracy. The program is comprised of three tasks: (1) computer program review and operations; (2) analysis and data correlations; and (3) documentation.

  18. Fluocinolone acetonide intravitreal implant (Iluvien®): in diabetic macular oedema.

    PubMed

    Sanford, Mark

    2013-02-01

    Fluocinolone acetonide intravitreal implant (Iluvien®) is an injectable, non-erodible, corticosteroid implant that is approved in several European countries for the treatment of chronic diabetic macular oedema (DMO). In analyses of two multinational trials in patients with DMO previously treated with macular laser photocoagulation, fluocinolone acetonide intravitreal implant 0.2 μg/day was significantly more efficacious than sham injection in improving visual acuity. At 24 months post injection, 29 % of fluocinolone acetonide intravitreal implant 0.2 μg/day recipients had an improvement in the best-corrected visual acuity (BCVA) letter score of ≥15 compared with 16 % in the sham injection group (p = 0.002) [primary endpoint]. Treatment benefit was most evident in the subgroup of patients whose duration of DMO was ≥3 years. In this subgroup at 36 months, 34 % of fluocinolone acetonide intravitreal implant 0.2 μg/day recipients had an increase in the BCVA score of ≥15, compared with 13 % of sham injection recipients (p < 0.001). Fluocinolone acetonide intravitreal implant recipients also had generally greater benefits than sham injection recipients on secondary endpoints. In patients who were phakic in the study eye at baseline, cataracts occurred in 82 % of fluocinolone acetonide intravitreal implant 0.2 μg/day recipients and 51 % of sham injection recipients. Overall, 37 % and 12 % of patients in the fluocinolone acetonide intravitreal implant and sham injection groups developed raised intraocular pressure (IOP), which was generally controlled with IOP-lowering drugs.

  19. SAFETY OF INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX): The SAFODEX study. Incidence and Risk Factors of Ocular Hypertension.

    PubMed

    Malclès, Ariane; Dot, Corinne; Voirin, Nicolas; Vié, Anne-Laure; Agard, Émilie; Bellocq, David; Denis, Philippe; Kodjikian, Laurent

    2017-07-01

    To analyze the incidence, risk factors, and time course of intraocular pressure elevation after intravitreal dexamethasone implant (Ozurdex). The medical charts of 421 consecutive eyes (361 patients) receiving one or more Ozurdex implant between October 2010 and February 2015 were reviewed retrospectively. Ocular hypertension was defined as intraocular pressure of at least 25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were retinal vein occlusion (34%), diabetic macular edema (30%), postsurgical macular edema (17%), uveitis (14%), and other etiologies (5%). Among 1,000 intravitreal injections, ocular hypertension was recorded for 28.5% of injected eyes over a mean follow-up period of 16.8 months (3-55). Intraocular pressure-lowering medication was required for 31% of eyes. Only three eyes with preexisting glaucoma required filtering surgery to manage postinjection intraocular pressure elevation. Early retreatment between the third and fourth month does not increase the risk of intraocular pressure elevation. Younger age, male sex, Type 1 diabetes, preexisting glaucoma treated with dual or triple therapy, and a history of retinal vein occlusion or uveitis were significant risk factors for ocular hypertension after dexamethasone implant injection (P < 0.05 for all the above). Episodes of ocular hypertension after Ozurdex implant were generally transient and successfully managed with topical treatment. An analysis of the risk factors may help to determine the risk-benefit ratio for individual patients treated with dexamethasone implants.

  20. Self-assembled phenylalanine-α,β-dehydrophenylalanine nanotubes for sustained intravitreal delivery of a multi-targeted tyrosine kinase inhibitor.

    PubMed

    Panda, Jiban J; Yandrapu, Sarath; Kadam, Rajendra S; Chauhan, Virander S; Kompella, Uday B

    2013-12-28

    Current standard of care for sustained back of the eye drug delivery is surgical placement or injection of large, slow release implants using a relatively large 22 gauge needle. We designed novel dipeptide (phenylalanine-α,β-dehydrophenylalanine; Phe-∆Phe) based nanotubes with a diameter of ~15-30 nm and a length of ~1500 nm that could be injected with a 33 gauge needle for sustained intravitreal delivery of pazopanib, a multi-targeted tyrosine kinase inhibitor. The drug could be loaded during nanotube assembly or post-loaded after nanotube formation, with the former being more efficient at 25% w/w pazopanib loading and ~55% loading efficiency. Plain and peptide loaded nanotube were non-cytotoxic to retinal pigment epithelial cells even at a concentration of 200 μg/ml. Following intravitreal injection of fluorescently labeled nanotubes using a 33 gauge needle in a rat model, the nanotube persistence and drug delivery were monitored using noninvasive fluorophotometry, electron microscopy and mass spectrometry analysis. Nanotubes persisted in the vitreous humor during the 15 days study and pazopanib levels in the vitreous humor, retina, and choroid-RPE at the end of the study were 4.5, 5, and 2.5-folds higher, respectively, compared to the plain drug. Thus, Phe-∆Phe nanotubes allow intravitreal injections with a small gauge needle and sustain drug delivery. © 2013.

  1. Solenoid pumps for flow injection analysis.

    PubMed

    Weeks, D A; Johnson, K S

    1996-08-01

    Methods employing flow injection analysis (FIA), particularly for in situ seawater techniques, would benefit from reduction in pump size and power requirement, longer maintenance intervals, and the ability to incorporate microprocessor control of each reagent and sample flow stream. In this work, the peristaltic pump of a conventional FIA system was replaced by three solenoid-driven diaphragm pumps with integral Viton check valves, and the system was tested by performing the simple nitrite analysis, which has well-defined FIA performance characteristics. Sixty injections per hour were possible with flow rates of 0.5 mL/min for reagents and sample. The coefficient of variation was 1% for 10 μM NO(2)(-) concentrations, and the detection limit was less than 0.1 μM NO(2)(-). These values match the reported performance for this method using peristaltic pumps.

  2. Intravitreal diclofenac versus intravitreal bevacizumab in naive diabetic macular edema: a randomized double-masked clinical trial.

    PubMed

    Soheilian, Masoud; Karimi, Saeed; Ramezani, Alireza; Montahai, Talieh; Yaseri, Mehdi; Soheilian, Roham; Peyman, Gholam A

    2015-06-01

    The purpose of the study is to compare single injection of intravitreal diclofenac (IVD) with intravitreal bevacizumab (IVB) in the treatment of eyes with naïve diabetic macular edema (DME). In this randomized clinical trial, 57 eyes of 57 patients were randomly assigned to IVD group (30 eyes), cases who received a single intravitreal injection of diclofenac (500 μg/0.1 ml), and IVB group (27 eyes), cases who received a single intravitreal injection of bevacizumab (1.25 mg). Change in best-corrected visual acuity in logMAR at week 12 was the primary outcome measure. Secondary outcomes included changes in central macular thickness, macular leakage, and potential injection-related complications. Best-corrected visual acuity improved significantly more in the IVD group than in the IVB group (P = 0.033), from 0.57 ± 0.25 to 0.49 ± 0.31 versus 0.55 ± 0.24-0.59 ± 0.27 logMAR at 12 weeks, respectively. However, the difference of macular thickness changes was in favor of IVB, but not to a significant level. The amount of change in leakage was not significantly different between the groups either. None of the eyes, in either group, developed ocular hypertension (≥23 mmHg) or cataract progression. No important injection-related complication was observed during the study period. This study demonstrated the superiority of IVD over IVB in the treatment of naïve DME regarding functional, but not anatomical outcomes. Therefore, using IVD as an adjunct or even alternative to other treatments might enhance the functional outcomes in such cases. Further studies are warranted to confirm potential benefit of IVD observed in this study.

  3. Residual ozone determination by flow injection analysis

    SciTech Connect

    Straka, M.R.; Pacey, G.E.; Gordon, G.

    1984-09-01

    It has been proposed that ozone be used to replace free chlorine for the disinfection of drinking water and waste water. For the use of ozone in this capacity, it would be necessary to have a fast accurate and precise method to analyze for the presence of residuals. An automated method for ozone determination based on the indigo reagent method is presented. This method is based on the advantages of flow injection analysis (FIA) techniques. 19 references, 3 tables, 2 figures.

  4. Successful Resolution of Preretinal Haemorrhage with Intravitreal Ranibizumab

    PubMed Central

    Noorlaila, Baharuddin; Raja-Azmi, Mohd-Noor

    2016-01-01

    We would like to report two cases of preretinal haemorrhage from two different aetiology courses of bleeding being treated with intravitreal ranibizumab and its outcome. Our first case was a 39-year-old man with a diagnosis of severe aplastic anaemia that presented with bilateral premacular haemorrhages in both eyes. His right eye vision was 6/45 and it was counting finger in the left eye. He was treated with intravitreal ranibizumab once to the right eye and twice to the left eye. Right eye showed complete resolution of premacular haemorrhage and minimal residual premacular haemorrhage in the left eye at 3 months after initial presentation. Our second case was a 32-year-old healthy teacher that presented with preretinal haemorrhage at superotemporal region extending to macular area in left eye secondary to valsalva retinopathy. Her left vision was counting finger. She was treated with single intravitreal ranibizumab to the left eye. There was significant reduction of premacular haemorrhage and her left eye vision improved to 6/6 at 10 weeks after injection. Both cases had favourable outcome with intravitreal ranibizumab and can be considered as nonsurgical treatment option in treating premacular haemorrhage. PMID:27800200

  5. Treatment of noninfectious posterior uveitis with dexamethasone intravitreal implant

    PubMed Central

    Myung, Jane S; Aaker, Grant D; Kiss, Szilárd

    2010-01-01

    Purpose To report our experience with dexamethasone 0.7 mg sustained-release intravitreal implant (Ozurdex®; Allergan, Inc, Irvine, CA) in noninfectious posterior uveitis. Methods A retrospective chart review of patients with noninfectious uveitis treated with sustained-release dexamethasone 0.7 mg intravitreal implant was performed. Complete ophthalmic examination including signs of inflammatory activity, visual acuity, fundus photography, fluorescein angiography, optical coherence tomography, and tolerability of the implant were assessed. Results Six eyes of 4 consecutive patients treated with a total of 8 dexamethasone 0.7 mg sustained-release intravitreal implants for posterior noninfectious uveitis were included. Two patients presented with unilateral idiopathic posterior uveitis; 2 patients had bilateral posterior uveitis, one secondary to sarcoidosis and the other to Vogt-Koyanagi-Harada syndrome. All eyes showed clinical and angiographic evidence of decreased inflammation following implant placement. Mean follow-up time post-injection was 5.25 months. Four eyes received 1 and 2 eyes received 2 Ozurdex implants during the follow-up period. The duration of effect of the implant was 3 to 4 months. No serious ocular or systemic adverse events were noted during the follow-up period. Conclusions In patients with noninfectious posterior uveitis, sustained-release dexamethasone 0.7 mg intravitreal implant may be an effective treatment option for controlling intraocular inflammation. PMID:21188153

  6. Intravitreal silicon-based quantum dots as neuroprotective factors in a model of retinal photoreceptor degeneration.

    PubMed

    Olson, Jeffrey L; Velez-Montoya, Raul; Mandava, Naresh; Stoldt, Conrad R

    2012-08-17

    To study the intravitreal application of silicon quantum dots (QDs) and their capabilities to deliver electrical stimulation to the retinal cells and to assess the potential effect on retinal electrophysiology and anatomy. A Royal College of Surgeon rat model of retinal degeneration was used in this study. A total of 32 eyes were used, divided in four groups of 8 eyes each; the first group received the silicon-based QD, the second group received an inactive gold-based QD, the third group received a sham injection, and the fourth group was used as a control. An electroretinogram (ERG) was done at baseline and thereafter every week for 9 weeks. At the end of the follow-up, eyes were collected for further pathologic analysis and nuclei cell counts. Eyes within the silicon-based QD group showed a definite but transient increase in the waves of the ERG, especially in the rod response compared with the sham and control groups (P < 0.05). The pathologic examination demonstrated a higher nuclei count in the QD group, consistent with a higher cell survival rate than that in the sham and control groups in which cells degenerated as expected. Intravitreal injection of silicon-based QD seems to be safe and well tolerated, with no evident toxic reaction and demonstrates a beneficial effect by prolonging cell survival rate and improving ERG patterns in a well-established model of retinal degeneration. (ClinicalTrials.gov numbers NCT00407602, NCT01490827.).

  7. Safety of intravitreal quinupristin/dalfopristin in an animal model

    PubMed Central

    Giordano, Veronica E.; Hernandez-Da Mota, Sergio E.; Adabache-Guel, Tania N.; Castillejos-Chevez, Armando; Corredor-Casas, Sonia; Salinas-Longoria, Samantha M.; Romero-Vera, Rafael; Jimenez-Sierra, Juan M.; Guerrero-Naranjo, Jose L.; Morales-Canton, Virgilio

    2016-01-01

    AIM To determine whether different intravitreal doses of quinupristin/dalfopristin lead to electroretinographic or histological changes in the rabbit retina over one month period after injection. METHODS Eighteen New Zealand white rabbits were divided into three treatment groups (groups 1 to 3) and different intravitreal doses of quinupristin/dalfopristin were tested in each group. The right eye was injected with the drug and the left eye received intravitreal injection of 5% dextrose water and served as control eye. The doses delivered to each group were 0.1 mg/0.1 mL, 1 mg/0.1 mL and 10 mg/0.1 mL. Simultaneous, bilateral, dark-adapted electroretinography and clinical images of both eyes were obtained in all groups before injection (baseline) and after 7, 14, 21 and 28d, followed by enucleation for histological examination. RESULTS Subjects in the group 1 showed no signs of toxicity in the electroretinogram when compared with groups 2 and 3 (Kruskall-Wallis test, P=0.000). By day 7, no electrical response to light stimuli was recorded in the treated eyes in groups 2 and 3, consistent with severe damage due to retinal toxicity. Light microscopy revealed no significant histopathological changes in the group 1, while rabbits in groups 2 and 3 had signs of granulomatous inflammation in most cases. CONCLUSION Intravitreal 0.1 mg/0.1 mL doses of quinupristin/dalfopristin do not lead to electroretinographic or histological signs of retinal toxicity compared with 1 mg/0.1 mL and 10 mg/0.1 mL in this rabbit model. PMID:27158605

  8. [Intravitreal bevacizumab in the treatment of idiopathic juxtafoveal telangiectasis type I].

    PubMed

    García-Ben, A; Gómez-Ulla, F; Rodriguez-Cid, M J

    2014-07-01

    We report a case of a 42 year-old male with a macular edema due to idiopathic juxtafoveal retinal telangiectasis type i, treated with 3 sequential injections of intravitreal bevacizumab (1.25 mg in 0.05 ml). Anatomical improvements were observed after one year of follow up. There is currently no general consensus regarding the treatment of unilateral idiopathic juxtafoveal telangiectasis. The therapeutic options are, grid laser photocoagulation, intravitreal triamcinolone, verteporfin photodynamic therapy, or anti-VEGF. Visual acuity and anatomical improvements were observed in this case after intravitreal bevacizumab. Thus, intravitreal bevacizumab seems to be effective to treat macular edema in idiopathic juxtafoveal telangiectasis type i. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  9. Intravitreal aflibercept versus intravitreal ranibizumab for the treatment of diabetic macular edema

    PubMed Central

    Fouda, Sameh Mosaad; Bahgat, Ahmed M

    2017-01-01

    Purpose The purpose of this study was to compare the efficacy of intravitreal aflibercept and ranibizumab in the treatment of diabetic macular edema (DME) in eyes with moderate visual loss. Patients and methods This study is a randomized prospective study. Seventy eyes with DME were divided into two groups (each containing 35 eyes). Eyes in group I were treated with intravitreal injection of 2 mg/0.05 mL aflibercept and eyes in group II were treated with intravitreal injection of 0.5 mg/0.1 mL ranibizumab. All the eyes had three successive injections as a loading dose (with 1 month interval), and then the patients were followed up monthly for 12 months. The outcomes of the study were visual acuity, central macular thickness (CMT), and the number of re-injections of the drug. Results Mean age of the patients in group I was 55.05±4.7 years and in group II was 56.64±5.8 years (P=0.17). The mean baseline best corrected visual acuity (BCVA) of eyes treated with aflibercept was 0.17±0.05 and with ranibizumab was 0.18±0.04 (P=0.9). BCVA was improved in both the groups at the end of the follow-up period and was found to be 0.42±0.28 and 0.37±0.23, respectively (P=0.27). The mean baseline CMT of eyes in group I was 465.29±33.7 µm and in group II was 471.5±34.4 µm (P=0.65). CMT decreased in both the groups to 360.8±85.7 µm and 387.3±87.8 µm, respectively (P=0.2). The mean number of drug re-injection was 2.62±0.68 and 3.03±0.95 in both the groups, respectively (P=0.02). Conclusion Aflibercept and ranibizumab have the same efficacy in the treatment of DME in eyes with moderate visual loss but with less number of drug re-injection and less treatment burden with aflibercept (2.62±0.68 versus 3.03±0.95). PMID:28356711

  10. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture.

    PubMed

    Arevalo, J Fernando; Sanchez, Juan G; Lasave, Andres F; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A; Restrepo, Natalia; Berrocal, Maria H; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy.

  11. Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity.

    PubMed

    Quiroz-Mercado, Hugo; Martinez-Castellanos, Maria A; Hernandez-Rojas, Myriam L; Salazar-Teran, Nelida; Chan, Robinson Vernon Paul

    2008-03-01

    To evaluate the role of antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity (ROP). In this noncomparative, prospective, interventional case series, bevacizumab was injected into the vitreous of patients with ROP in three different groups: group I, patients with stage IVa or IVb ROP who had no response to conventional treatment; group II, patients with threshold ROP who were difficult to treat with conventional therapy because of poor visualization of the retina; and group III, patients with high-risk prethreshold or threshold ROP. Thirteen patients (18 eyes; mean age +/- SD, 4 +/- 3 months; mean follow-up, 6 months) were included in the study. We found neovascular regression in 17 eyes. One patient with stage IVa ROP had spontaneous retinal reattachment after an intravitreal injection of bevacizumab. There were no serious ocular or systemic adverse events. The use of bevacizumab may be promising in the treatment of patients with ROP. Further studies need to be performed to determine the safety and long-term efficacy of intravitreal injection of bevacizumab, either as first-line therapy or after failure of conventional therapy.

  12. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    PubMed Central

    Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

  13. Intravitreal toxicity of dental adhesives in the rabbit.

    PubMed

    Ciulla, T A; Haimovici, R; Riley, E J; D'Amico, D J

    1996-01-01

    The authors tested the intravitreal toxicity of four commonly employed dental adhesives to determine their suitability as retinal adhesives. Two glass ionomers, a polycarboxylate, and a composite resin (Ketac-Bond Radiopaque Poly Maleic Acid [ESPE, Oberbay, Germany], Vitrebond Light Cure Glass Ionomer [3M, St. Paul, MN], Carbchem Zinc Polycarboxylate Cement [PSP Dental Company, Kent, United Kingdom], and Kerr Porcelite Dual Cure [Kerr, Romulus, MI]) were reconstituted according to the manufacturer's recommendations, and 0.1 mliter was injected separately into the vitreous cavity of New Zealand white rabbits. Serial slit-lamp and funduscopic evaluations were performed up to 3 months after injection. Selected eyes were studied angiographically and histopathologically. Intravitreal administration of the glass ionomers Ketac-bond or Vitrebond lead to intense vitritis within the first weeks. Necrotic retinal detachments ultimately developed in these eyes, along with those administered the polycarboxylate cement Carbchem. Eyes injected with the composite resin Porcelite Dual Cure showed no ophthalmoscopic evidence of vitreous or retinal toxicity and no angiographic evidence of vascular toxicity. Histopathology of the eyes with this intravitreal composite resin cement revealed mild disorganization of photoreceptor nuclei and outer segments. Among the agents studied, the dual-cure composite resin cement Porcelite showed the least ocular toxicity. Further studies to evaluate its intraocular toxicity and efficacy as a retinal adhesive are warranted.

  14. Choroidal Thickness Changes After Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration.

    PubMed

    Minnella, Angelo Maria; Federici, Matteo; Falsini, Benedetto; Barbano, Lucilla; Gambini, Gloria; Lanza, Angela; Caporossi, Aldo; Savastano, Maria Cristina

    2016-08-01

    The results regarding changes of choroidal thickness following intravitreal ranibizumab injections in the literature are controversial. Vascular endothelial growth factor A is implicated in pathogenesis of neovascular age-related macular degeneration (AMD). The suspected unchanged choroidal layer thickness after intravitreal injections of ranibizumab suggests a possible protection of the outer blood-retinal barrier in the human eye. The aim was to evaluate choroidal thickness following the first administration of the study drug ranibizumab into the eyes of naïve wet AMD patients (nAMD). In this open label, 3-month, prospective, single-center, interventional, single-arm pilot study, 20 nAMD eyes were included and underwent three consecutive monthly injections of ranibizumab (0.5 mg/0.05 ml). Vital signs (i.e., blood pressure and pulse), ophthalmic examinations, intraocular pressure, best correct visual acuity and subfoveal choroidal thickness as examined with optical coherence tomography using enhanced depth imaging (OCT-EDI) were assessed at each visit. All patients were evaluated at baseline and at 15, 30 60 and 90 days after intravitreal injection. Ten eyes with fibrotic AMD lesions were evaluated as the control group. In all eyes, the choroidal thicknesses (µm) exhibited no significant changes from the baseline visit to the visits at 15, 30, 60 and 90 days post-injection (P > 0.05). The intravitreal treatment with ranibizumab was well tolerated, and no adverse events were registered. Choroidal thickness appeared to be unmodified following the intravitreal injection of ranibizumab into nAMD eyes. Intravitreal ranibizumab injections probably elicit a pharmacologic effect only in the choroidal neovascularization and not in the choroid circulation under neovascular lesions. Clinical Trials Eudract Registration #: 2013-005091-17.

  15. Intravitreal aflibercept treatment in eyes with exudative age-related macular degeneration following prior treatment with intravitreal ranibizumab

    PubMed Central

    Narayan, Daniel Sanju; Muecke, James

    2015-01-01

    Background: To investigate visual and anatomical outcomes in eyes with exudative age-related macular degeneration treated with intravitreal aflibercept following prior treatment with intravitreal ranibizumab. Materials and Methods: Retrospective, single-center study of 192 eyes treated with 0.5 mg intravitreal ranibizumab every 4 weeks for three consecutive doses followed by a variable dose schedule. After more than 12 months of ranibizumab treatment, eyes that required ranibizumab injections at 4-week or 6-week intervals were switched to aflibercept therapy. Results: After 12–69 months (42 months ± 18 months, mean ± standard deviation [SD]) of treatment with intravitreal ranibizumab, 80 eyes were changed to 2 mg intravitreal aflibercept treatment with follow-up after 12–18 months (16 months ± 1 month, mean ± SD). Thirty-nine eyes had persistent macular fluid after treatment with ranibizumab. Mean logMAR visual acuity (VA) in eyes treated with ranibizumab changed by − 0.089 ± 0.310 (mean ± SD; P = 0.0003), which correlates to an approximate gain of 4.5 letters. The number of eyes with macular fluid decreased from 39 to 23 after aflibercept treatment. Mean logMAR VA in eyes with intraretinal macular fluid treated with aflibercept changed by −0.079 ± 0.134 (mean ± SD; P = 0.006), which correlates to an approximate gain of 4 letters. Mean logMAR VA in eyes with submacular fluid was not significantly different after aflibercept treatment. Conclusion: Eyes with persistent intraretinal macular fluid had visual and anatomic response after changing from ranibizumab to aflibercept treatment. PMID:26669334

  16. The efficacy of intravitreal bevacizumab for acute central serous chorioretinopathy.

    PubMed

    Aydin, Erdinc

    2013-02-01

    To investigate the efficacy of intravitreal bevacizumab injection in patients with acute central serous chorioretinopathy (CSCR). Between 6 weeks and 3 months, 13 eyes of 22 patients with acute CSCR received an intravitreal bevacizumab injection (2 mg/0.08 mL), 9 eyes had no medical treatment as a control. At baseline and follow-up visits patients had best corrected visual acuity (BCVA), intraocular pressure assessment, dilated fundus examination, and spectral optical coherence tomography imaging. Outcome measures were the resolution of neurosensory detachment, improvement in visual acuity, and symptoms. All patients showed prompt improvements of visual acuity and symptoms until the 3rd month and recovered from neurosensory detachment gradually following treatment in the study group. The vision of control subjects recovered later and the regression of serous retinal detachments were fairly slow. The mean BCVA improved from 0.39±0.16 at first visit (at baseline) to 0.73±0.17 at the 6th month in the study group; and, from 0.25±0.17 at first visit (at baseline) to 0.67±0.13 at the 6th month in the control group that was statistically significant (P=0.0001; P=0.0001, respectively). Mean retinal thickness for the study group was decreased from 414.38±102.79 at first visit (at baseline) to 256.46±84.77 at the 3rd month and 198.30±29.81 at the 6th month (P=0.0001, P=0.0001); and that for the control group was decreased from 510.33±80.59 at first visit (at baseline) to 336.33±127.83 at the 3rd month and 205.66±19.65 at the 6th month (P=0.004, P=0.0001, respectively). One of the patients in the control group revealed recurrence at the 6th month and the patient was given intravitreal injection of bevacizumab. Intravitreal bevacizumab injection for acute CSCR can lead to remarkable improvements of visual acuity within 3 months follow-up compared with controls. These results demonstrated that intravitreal bevacizumab injection may be a promising option for

  17. Intravitreal Adalimumab for the Control of Breakthrough Intraocular Inflammation.

    PubMed

    Kheir, Wajiha J; Mehanna, Carl-Joe; Abdul Fattah, Maamoun; Al Ghadban, Sara; El Sabban, Marwan; Mansour, Ahmad M; Hamam, Rola N

    2017-09-14

    Investigate the efficacy of intravitreal adalimumab in breakthrough panuveitis in patients on systemic adalimumab for more than 3 months. Retrospective study of patients on systemic adalimumab with breakthrough panuveitis requiring intravitreal adalimumab therapy. Seven eyes of four patients with Adamantiades-Behçet disease panuveitis were included and all were maintained on systemic adalimumab for 7.3 months (range 3-11) with inflammation controlled for 4.1 months (range 2-10) before breakthrough uveitis. The total number of attacks was 13 over 24.5 months (range 12-30). Resolution of attack was defined as return to baseline visual acuity with resolution of inflammatory markers. Three attacks resolved after only one injection and 10 attacks required an average of 2.4 injections (range 2-3). No systemic or ocular complications were noted. Intravitreal adalimumab warrants further investigation as a potentially effective, practical and safe adjunctive therapy for the control of breakthrough inflammation in select patients maintained on systemic adalimumab.

  18. Intravitreal Dexamethasone Implant (Ozurdex) for Refractory Macular Edema Secondary to Retinitis Pigmentosa

    PubMed Central

    Örnek, Nurgül; Örnek, Kemal; Erbahçeci, İnci Elif

    2016-01-01

    Macular edema (ME) in retinitis pigmentosa (RP) often impairs central vision dramatically. A 41-year-old woman diagnosed with RP was referred to our outpatient clinic due to severe visual deterioration in both eyes. The patient was treated with topical carbonic anhydrase inhibitors, topical corticosteroids and intravitreal triamcinolone acetonide injections, but her ME recurred. Intravitreal 0.7 mg dexamethasone implant (Ozurdex, Allergan) was administered into both eyes without complications. On the fourth day after both injections, visual acuity improved and ME almost totally resolved. No recurrence was observed at follow-up six months later. PMID:28058154

  19. [Subretinal neovascular membrane in angioid streaks treated with intravitreal bevacizumab].

    PubMed

    García-López, A; González-Castaño, C

    2014-05-01

    Angioid streaks are breaks in Bruch's membrane that may be associated, among others, with pseudoxanthoma elasticum. Its most common complication is the development of subretinal neovascular membranes (SRNVM) and the decreased vision this entails. A 28 year old woman with angioid streaks and SRNVM in the left eye, who received 3 injections of intravitreal bevacizumab, with rapid improvement in vision and stability during 11 months follow up. The finding of angioid streaks led to the diagnosis of pseudoxanthoma elasticum. Intravitreal bevacizumab should be considered as an effective treatment option for choroidal neovascularization associated with angioid streaks. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  20. Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema

    PubMed Central

    Spandau, U H M; Derse, M; Schmitz-Valckenberg, P; Papoulis, C; Jonas, J B

    2005-01-01

    Aim: To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular oedema. Methods: The prospective, randomised, double masked, clinical interventional study included 27 eyes (27 patients) with diffuse diabetic macular oedema. They were randomly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9), respectively. Dosage measurement was performed before filtration. Mean follow up was 6.6 (SD 2.4) months (3–12 months). Main outcome measures were visual acuity and intraocular pressure. Results: Maximal increase in visual acuity was significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used (p = 0.77). Conclusions: In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used. PMID:16024853

  1. Recent advances in flow injection analysis.

    PubMed

    Trojanowicz, Marek; Kołacińska, Kamila

    2016-04-07

    A dynamic development of methodologies of analytical flow injection measurements during four decades since their invention has reinforced the solid position of flow analysis in the arsenal of techniques and instrumentation of contemporary chemical analysis. With the number of published scientific papers exceeding 20,000, and advanced instrumentation available for environmental, food, and pharmaceutical analysis, flow analysis is well established as an extremely vital field of modern flow chemistry, which is developed simultaneously with methods of chemical synthesis carried out under flow conditions. This review work is based on almost 300 original papers published mostly in the last decade, with special emphasis put on presenting novel achievements from the most recent 2-3 years in order to indicate current development trends of this methodology. Besides the evolution of the design of whole measuring systems, and including especially new applications of various detections methods, several aspects of implications of progress in nanotechnology, and miniaturization of measuring systems for application in different field of modern chemical analysis are also discussed.

  2. The structural effect of intravitreal Brilliant blue G and Indocyanine green in rats eyes.

    PubMed

    Ooi, Y L; Khang, T F; Naidu, M; Fong, K C S

    2013-03-01

    To compare the potential retinal toxicity of two commercially Brilliant blue G dyes (Brilliant Peel and Ocublue Plus) and Indocyanine green (ICG) at usual clinical concentration. Brilliant Peel 0.025% (n=9), Ocublue Plus 0.025% (n=9), and ICG 0.05% (n=9) were injected intravitreally into Sprague-Dawley rat left eyes with balanced salt solution injected in the contralateral eyes as control. Evaluation of the effect of the dyes on retinal architecture was done by histological analysis of neurosensory retinal thickness and retinal ganglion cell (RGC) counts 7 days after intravitreal injection. Paired t-test was done to detect the presence of biologically significant thinning in neurosensory retina and five retinal layers for each dye (paired t-tests). One-way ANOVA and Tukey's Honestly Significant Difference test were used to assess whether different dyes caused significant thinning in mean neurosensory retinal thickness and reduction of mean RGC density. Eyes treated with ICG had significantly thinner mean total neurosensory retinal thickness compared with the control eyes (P-value=0.01), followed by those treated with Ocublue Plus (P-value=0.03). Brilliant Peel did not cause significant thinning in any of the five retinal layers (all P-values>0.05). No significant difference in mean thinning of the total retinal thickness was detected between dyes (P-value=0.11). The mean thickness of the photoreceptor outer segment and outer plexiform layers were significantly reduced in ICG-injected eyes when compared with the control eyes (P-value=0.02). No significant difference in mean thinning between the three dyes was detected at all five retinal layers using one-way ANOVA (all P-values>0.35). RGC density was significantly reduced for ICG (P-value=0.01) but only marginally for Ocublue Plus (P-value=0.05). No significant reduction in RGC density was observed for Brilliant Peel (P-value=0.2). Intravitreal Brilliant Peel is safe to rats retina. The retinal thinning and

  3. The structural effect of intravitreal Brilliant blue G and Indocyanine green in rats eyes

    PubMed Central

    Ooi, Y L; Khang, T F; Naidu, M; Fong, K C S

    2013-01-01

    Purpose To compare the potential retinal toxicity of two commercially Brilliant blue G dyes (Brilliant Peel and Ocublue Plus) and Indocyanine green (ICG) at usual clinical concentration. Methods Brilliant Peel 0.025% (n=9), Ocublue Plus 0.025% (n=9), and ICG 0.05% (n=9) were injected intravitreally into Sprague–Dawley rat left eyes with balanced salt solution injected in the contralateral eyes as control. Evaluation of the effect of the dyes on retinal architecture was done by histological analysis of neurosensory retinal thickness and retinal ganglion cell (RGC) counts 7 days after intravitreal injection. Paired t-test was done to detect the presence of biologically significant thinning in neurosensory retina and five retinal layers for each dye (paired t-tests). One-way ANOVA and Tukey's Honestly Significant Difference test were used to assess whether different dyes caused significant thinning in mean neurosensory retinal thickness and reduction of mean RGC density. Results Eyes treated with ICG had significantly thinner mean total neurosensory retinal thickness compared with the control eyes (P-value=0.01), followed by those treated with Ocublue Plus (P-value=0.03). Brilliant Peel did not cause significant thinning in any of the five retinal layers (all P-values>0.05). No significant difference in mean thinning of the total retinal thickness was detected between dyes (P-value=0.11). The mean thickness of the photoreceptor outer segment and outer plexiform layers were significantly reduced in ICG-injected eyes when compared with the control eyes (P-value=0.02). No significant difference in mean thinning between the three dyes was detected at all five retinal layers using one-way ANOVA (all P-values>0.35). RGC density was significantly reduced for ICG (P-value=0.01) but only marginally for Ocublue Plus (P-value=0.05). No significant reduction in RGC density was observed for Brilliant Peel (P-value=0.2). Conclusion Intravitreal Brilliant Peel is safe to rats

  4. Intravitreal toxicology and duration of efficacy of a novel antiviral lipid prodrug of ganciclovir in liposome formulation.

    PubMed

    Cheng, L; Hostetler, K Y; Chaidhawangul, S; Gardner, M F; Beadle, J R; Keefe, K S; Bergeron-Lynn, G; Severson, G M; Soules, K A; Mueller, A J; Freeman, W R

    2000-05-01

    To evaluate the intraocular safety and antiviral treatment efficacy of the sustained lipid prodrug of ganciclovir, 1-O-hexadecylpropanediol-3-phospho-ganciclovir (HDP-P-GCV), as an intravitreal injectable drug system for viral retinitis. HDP-P-GCV was synthesized by coupling 1-O-hexadecyl-propanediol-3-phosphate to either free hydroxyl of ganciclovir in pyridine with dicyclohexylcarbodiimide as catalyst. The compound was formulated into liposomes. The antiviral activity was assessed by DNA reduction in vitro, and intraocular safety was assessed by ophthalmoscopy, electrophysiology, and histology after intravitreal injections, with resultant intravitreal concentrations of 0.2, 0.632, 1.12, and 2 mM. The treatment efficacy was evaluated by simultaneous intravitreal injection of HDP-P-GCV and herpes simplex virus type 1 (HSV-1) or by intravitreal injection of HDP-P-GCV at various times before HSV-1 intravitreal inoculation. Retinitis was scored with ophthalmoscopy and compared with controls. In vitro, the IC50 of HDP-P-GCV against HSV-1 and human cytomegalovirus (HCMV) infected cells was 0.02 and 0.6 microM, respectively. In rabbits in vivo, HDP-P-GCV dispersed evenly and maintained a good vitreous clarity at all doses except 2 mM final intravitreal concentration. Although cataracts were observed in some eyes at the higher doses, they were not observed in eyes with 0.2 mM final intravitreal concentration. No other indications of ocular toxicity were observed. Intravitreal injection of HDP-P-GCV with resultant 0.2 mM intravitreal concentration in the HSV-1 retinitis rabbit model demonstrated a complete protection of the retina with the simultaneous treatment strategy and a 4 (P = 0.03) to 6-(P = 0.058) week significant protection of retina with the pretreatment strategies when compared with ganciclovir or blank liposome controls. In the rabbit model of HSV-1 retinitis HDP-P-GCV acts as a long-lasting intravitreal injectable anti-CMV or anti-HSV compound. This self

  5. The duration of effect of centrifuge concentrated intravitreal triamcinolone acetonide.

    PubMed

    Ober, Michael D; Valijan, Sevak

    2013-04-01

    To estimate the duration of activity for intravitreal triamcinolone injected with a new technique using centrifuge concentration (Centrifuge concentrated IntraVitreal Triamcinolone, C-IVT). All injections were performed by a single surgeon (M.D.O.) using a 30-gauge needle. A vial of Triesence (triamcinolone; Alcon Laboratories, Fort Worth, TX) was drawn into a 1-mL syringe and the plunger cut off. The contents were spun in a centrifuge, and a second plunger was placed. Records of all patients receiving C-IVT with 0.05 mL or 0.1 mL from January 1, 2009, through December 31, 2009, were retrospectively reviewed. Eighty-four injections from 69 eyes of 57 patients were included. Sixty-nine injections from 54 eyes of 44 patients received 0.05 mL of C-IVT, whereas 15 injections from 15 eyes of 13 patients received 0.1 mL of C-IVT. Triamcinolone acetonide was still visualized in the vitreous on an average of 5.0 ± 2.4 months (median 5 months) after 0.05 mL of C-IVT and 8.3 ± 4.0 months (median 8 months) after 0.1 mL of C-IVT during follow-up visits. The longest duration recorded was 14 months for the 0.05-mL group and 18 months for the 0.l-mL group. The C-IVT results in a long duration of effect that seems to be greater than previously published techniques. It may be considered for patients requiring chronic steroid therapy, in which the benefits of long-term intravitreal steroids are believed to outweigh their risk.

  6. Intravitreal chemotherapy in the management of vitreous disease in retinoblastoma.

    PubMed

    Kiratli, Hayyam; Koç, İrem; Varan, Ali; Akyüz, Canan

    2017-06-26

    To evaluate the therapeutic outcome of intravitreal melphalan injection in the management of vitreous disease in patients with retinoblastoma. We particularly aimed to assess whether higher melphalan dose with lower number of injections was more effective and associated with fewer side effects. This retrospective, interventional, noncomparative, and nonrandomized study included 39 eyes of 37 patients. Vitreous seeds were classified as dust, sphere, and cloud types. Intravitreal injections were performed through pars plana free of any visible tumor using 30-G needle. Response of the seeds (disappearance, conversion into inactive debris, or progression) and enucleation rate were determined as outcome measures. All patients previously received systemic or intra-arterial chemotherapy. Vitreous seeding was primary in 54% of eyes and secondary in 46% of eyes. Vitreous seeds were classified as dust in 9 (23.1%) eyes, sphere in 24 (61.5%) eyes, and cloud in 6 (15.4%) eyes. Melphalan dose varied between 20 and 40 µg and 20 (51.3%) eyes received >30 µg. The total number of injections was 70 (range 1-5, mean 1.8 per eye). Various types of regression were obtained in 27 (69.2%) eyes. Sphere-type seeds were the most responsive to melphalan. Nonresponse and disease progression were noted in 12 (30.8%) eyes. After a mean follow-up of 11.8 months, 17 (44%) eyes were enucleated. Vitreous hemorrhage (18%) and retinal pigment epithelial alterations (8%) were the most common side effects. Intravitreal melphalan at 30-40 µg in 1 or 2 injections proved effective in 69.2% of eyes with vitreous disease.

  7. Retinal toxicity of intravitreal tenecteplase in the rabbit

    PubMed Central

    Rowley, S A; Vijayasekaran, S; Yu, P K; McAllister, I L; Yu, D-Yi

    2004-01-01

    Aim: To investigate the retinal toxicity of intravitreal injection of a novel fibrinolytic tenecteplase in rabbit eyes. Methods: Tenecteplase (25–350 μg in 0.1 ml BSS) was injected into the vitreous cavity of normal rabbit eyes. Control (fellow) eyes received 0.1 ml of BSS. One day, 1 week, and 2 months post-injection, the eyes were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and electroretinography, and then harvested for histopathological examination. Results: No evidence of retinal toxicity was seen with tenecteplase doses up to and including 50 μg. At a dose of 150 μg ophthalmoscopy was normal, but histology showed mild retinal damage in the inner nuclear layer and electroretinography showed a temporary reduction in B-wave amplitude. At doses of 200 μg and above, there was evidence of retinal toxicity on electroretinography, ophthalmoscopy, and histology. Ophthalmoscopic findings included vitreal fibrosis, retinal necrosis and tractional retinal detachment and light microscopy revealed necrosis of retinal pigment epithelium and other retinal layers. Damage was centred around the injection site but was more widespread with the higher doses. Conclusion: A dose of 50 μg tenecteplase appears safe for intravitreal injection in the rabbit. Tenecteplase could have potential applications in the treatment of submacular haemorrhage and retinal vein occlusion. PMID:15031179

  8. Analysis of the injection process in direct injected natural gas engines

    NASA Astrophysics Data System (ADS)

    Jennings, M. J.; Jeske, F. R.

    1993-08-01

    The analysis was based upon a series of three-dimensional computational fluid dynamics (CFD) calculations of natural gas (NG) injection in engine combustion chambers and constant volume chambers. Simulations of injection into constant volume chambers were used to investigate the fundamental behavior of NG jets. Calculations of engine injection, which include a moving piston, were used to study the effects of combustion system design.

  9. Safety of Intravitreally Administered Recombinant Erythropoietin (An AOS Thesis)

    PubMed Central

    Tsai, James C.

    2008-01-01

    Purpose This study investigated the safety and potential retinal toxicity of intravitreally administered erythropoietin (EPO) in a rodent animal model. Methods Forty-two healthy Sprague-Dawley rats were divided into one of 7 groups (N = 6 per group): control, sham injection, vehicle injection, and EPO injections of 50 ng (5 U), 100 ng (10 U), 250 ng (25 U), and 625 ng (62.5 U). Only the right eye was treated in each animal. Standard full-field dark- and light-adapted electroretinography (ERG) was obtained at 1 day prior to injection and then on postinjection days 3, 7, 14, and 21. Intraocular pressure (IOP) was measured at the conclusion of each ERG recording. Animals were sacrificed and the eyes underwent histologic examination with light microscopy and hematoxylin-eosin staining. Results Rod peak, scotopic, and photopic responses (amplitude and latency) were not statistically different in the animals receiving 50 to 100 ng EPO. In the 250-ng group, the photopic b-wave amplitude at day 21 was elevated (P <.05), whereas in the 625-ng group, the scotopic OP3 latency ratio was higher at baseline (P <.05). No significant histologic abnormalities were noted except for one animal (625-ng group) with qualitative differences in retinal layer thickness and cellular density. Conclusions Intravitreal administration of EPO (at doses up to 625 ng) does not cause adverse effects on retinal function as assessed by ERG. Moreover, single intravitreal dosing does not appear to elicit retinal neovascularization. Further investigation is warranted to assess fully the potential of this neuroprotective cytokine as a treatment for glaucoma. PMID:19277250

  10. Influence of the vitreomacular interface on the efficacy of intravitreal therapy for uveitis-associated cystoid macular oedema.

    PubMed

    Munk, Marion R; Ram, Radha; Rademaker, Alfred; Liu, Dachao; Setlur, Vikram; Chau, Felix; Schmidt-Erfurth, Ursula; Goldstein, Debra A

    2015-11-01

    To evaluate the effect of the vitreomacular interface (VMI) on treatment efficacy of intravitreal therapy in uveitic cystoid macular oedema (CME). Retrospective analysis of CME resolution, CME recurrence rate and monthly course of central retinal thickness (CRT), retinal volume (RV) and best corrected visual acuity (BCVA) after intravitreal injection with respect to the VMI configuration on spectral-domain OCT using chi-squared test and repeated measures anova adjusted for confounding covariates epiretinal membrane, administered drug and subretinal fluid. Fifty-nine eyes of 53 patients (mean age: 47.4 ± 16.9 years) were included. VMI status had no effect on complete CME resolution rate (p = 0.16, corrected p-value: 0.32), time until resolution (p = 0.09, corrected p-value: 0.27) or CME relapse rate (p = 0.29, corrected p-value: 0.29). Change over time did not differ among the VMI configuration groups for BVCA (p = 0.82) and RV (p = 0.18), but CRT decrease was greater and faster in the posterior vitreous detachment (PVD) group compared to the posterior vitreous attachment (PVA) and vitreous macular adhesion (VMA) groups (p = 0.04). Also, the percentage of patients experiencing a ≥ 20% CRT thickness decrease after intravitreal injection was greater in the PVD group (83%) compared to the VMA (64%) and the PVA (16%) group (p = 0.027), however, not after correction for multiple testing (corrected p-value: 0.11). The VMI configuration seems to be a factor contributing to treatment efficacy in uveitic CME in terms of CRT decrease, although BCVA outcome did not differ according to VMI status. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Analysis of Potential Ischemic Effect of Intravitreal Bevacizumab on Unaffected Retina in Treatment-Naïve Macular Edema Due to Branch Retinal Vein Occlusion: A Prospective, Interventional Case-Series.

    PubMed

    Rishi, Pukhraj; Raka, Neha; Rishi, Ekta

    2016-01-01

    To study potential ischemic effects of intravitreal Bevacizumab (IVB) on unaffected retina in treatment-naive eyes with macular edema secondary to branch retinal vein occlusion (BRVO) and contralateral eyes secondary to systemic absorption. Prospective, interventional series included 27 treatment-naive eyes with BRVO and macular edema. Eyes with diabetic retinopathy, glaucoma, vasculitides, papilledema or systemic neurologic condition. Subjects underwent complete ophthalmological examination including fluoroscein angiography (FA), optical coherence tomography (OCT) and multifocal electroretinogram (mf-ERG). All subjects received single 1.25 mg/0.05ml IVB injection. Two observers measured all parameters; inter-observer agreements were expressed as kappa values. Paired t-test was used to compare values at baseline and follow-up. The statistical analysis was done using SPSS for Windows, Version 14.0. (Chicago, SPSS Inc.) Presenting mean CFT (central foveal thickness) was 499.5(+/-229.7) μm, mean BCVA (best corrected visual acuity) was 0.64(+/-0.41) logMAR. At last follow-up, mean CFT was 267.9(+/-159.3) μm (P<0.001), 95% CI [127.18, 422.32]; mean BCVA was 0.28(+/-0.24) logMAR. Respectively, mean N1 and P1 amplitudes of mfERG in 'unaffected quadrant' at presentation were -6.10(+/-4.00) nV/deg2 and 17.17(+/-11.54)nV/deg2; and -5.33(+/-1.30)nV/deg2 and 15.29(+/-4.69)nV/deg2 at final follow-up (P = 0.631 and 0.197, respectively), (95% CIs [-0.93, 1.42] and [-4.22, 1.08] respectively). In fundus quadrant of fellow eyes corresponding to unaffected quadrant in treated eyes, mean N1 and P1 amplitudes at presentation were -5.39(+/-1.56)nV/deg2 and 15.89(+/-3.89)nV/deg2; and -5.39(+/-1.90)nV/deg2 and 15.9(+/-5.52)nV/deg2 (P = 0.380 and 0.208), (95% CIs [-0.57, 1.28] and [-4.1, 1.1]) at last follow-up, respectively. This study analysed the effects with a single injection of bevacizumab. However, whether ischemic adverse effects will emerge with repeated IVB injections as a

  12. Intravitreal bevacizumab in persistent retinopathy secondary to malignant hypertension.

    PubMed

    Salman, Abdelrahman Gaber

    2013-01-01

    To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) injection in persistent retinopathy secondary to malignant hypertension (MHT). Single IVB injection of 1.25 mg/0.05 ml in 12 cases with persistent retinopathy secondary to MHT more than one month after control of MHT with pre and post injection evaluation of best corrected visual acuity (BCVA) and anatomical outcome up to sixth month and postinjection complications were evaluated. Progressive reductions in retinal hemorrhages, exudates, cotton-wool spots, and macular star were documented by photography, angiography, and central macular thickness (CMT) measured by optical coherence tomography (OCT) imaging. Decreased macular edema was the most common finding. Improvement or stabilization of visual acuity was noted in all cases. In addition to proper medical management of MHT, IVB injection is an effective and safe approach to treat persistent retinopathy associated with MHT.

  13. Occlusive vasculitis due to hyperacute Streptococcus mitis endophthalmitis after intravitreal ranibizumab.

    PubMed

    Baxter, Kevin R; Robinson, Joshua E; Ruby, Alan J

    2015-01-01

    To report a case of hyperacute Streptococcus mitis endophthalmitis after intravitreal ranibizumab resulting in occlusive vasculitis. Retrospective case report with ultra-wide-field color fundoscopic and fluorescein angiographic imaging. An 83-year-old woman received an intravitreal injection of ranibizumab to her right eye and was evaluated the next day (less than 24 hours from the injection) because of acute loss of vision. Her vision had decreased from 20/50 to hand motions in the right eye at the time of reevaluation. Wide-field fundus photography demonstrated pallid optic nerve head edema, generalized vascular attenuation, diffuse vascular sheathing, and scattered large postequatorial intraretinal hemorrhages. Ultra-wide-field fluorescein angiography revealed a severely delayed AV transit time associated with extensive areas of retinal nonperfusion and late retinal vascular leakage consistent with occlusive vasculitis. She underwent immediate pars plana vitrectomy with extensive irrigation of the vitreous cavity and intravitreal injection of antibiotics. In light of a worsening clinical course, she was taken for repeat vitrectomy 1 week later with panretinal endolaser photocoagulation, instillation of silicone oil, and sub-Tenon triamcinolone acetonide. At postoperative month 1, she maintained 20/200 vision with improved retinal perfusion on fluorescein angiography. We describe a hyperacute case of S. mitis endophthalmitis after intravitreal injection with ranibizumab, associated with severe occlusive vasculitis on ultra-wide-field fluorescein angiography. Aggressive early surgical intervention may be associated with better outcomes than previously reported.

  14. Intravitreal bevacizumab: safety of multiple doses from a single vial for consecutive patients.

    PubMed

    Ng, Danny S; Kwok, Alvin K H; Chan, Clement W; Li, Walton W T

    2012-12-01

    To report the incidence of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor and the safety profile of multiple doses of bevacizumab from the same vial reused for multiple patients. Case series. A private hospital in Hong Kong. A systematic retrospective review of consecutive intravitreal anti-vascular endothelial growth factor injections between 5 June 2006 and 17 December 2010 at a single institute was conducted. Patients were identified from prospectively designed audit forms, and each patient's medical record was reviewed for any documented complications. Bevacizumab 1.25 mg/0.05 mL to 2.50 mg/0.1 mL was aspirated from the designated vial, with a maximum of 10 consecutive injections being aspirated from the same vial. The opened vial was then discarded without overnight storage. Ranibizumab was aspirated from the commercially available 1 mg/0.1 mL single-use vial. A total of 1655 intravitreal anti-vascular endothelial growth factor injections into 392 eyes of 383 patients were evaluated during the study period. There were 1184 bevacizumab injections and 471 ranibizumab injections. There was one case of suspected endophthalmitis after ranibizumab injection, though culture of the vitreous tap was negative. The point prevalence of endophthalmitis was 0.06% (1/1655) for the total number of injections: 0.21% (1/471) after ranibizumab, and 0% after bevacizumab. Although many centres aliquot multiple syringes from a single vial to be kept in a refrigerator for use, the current study shows that so long as proper sterile techniques are implemented, there were no cases of endophthalmitis from using the same vial, which was reused for a maximum of 10 consecutive injections. For intravitreal injection, bevacizumab costs approximately US$50 to US$100 per dose, as opposed to US$2000 per dose for ranibizumab. Sharing multiple doses of bevacizumab from a single vial can substantially reduce the cost of treatment.

  15. Detecting endotoxin contamination of ophthalmic viscosurgical devices: intracameral versus intravitreal assays in rabbits.

    PubMed

    Buchen, Shelley Y; Calogero, Don; Hilmantel, Gene; Eydelman, Malvina B

    2012-07-01

    To compare the sensitivities of intracameral and intravitreal assays in the rabbit model to determine the relative adequacy of these methods in detecting bacterial endotoxin contamination of ophthalmic viscosurgical devices (OVDs). Experimental, randomized animal study. Twenty New Zealand white rabbits. Rabbits were randomized into 4 groups to receive a cohesive or a dispersive OVD via intracameral or intravitreal injection. All 40 treated eyes (10 eyes of 5 animals in each group) received bilateral injection of OVD spiked with bacterial endotoxin at 7.0 endotoxin units/ml. All eyes were evaluated by slit-lamp biomicroscopy for inflammatory response at 3, 6, 9, 24, 48, and 72 hours after exposure. Eyes that received intravitreal injection were also dilated at 24, 48, and 72 hours and were re-examined by slit-lamp biomicroscopy and by indirect ophthalmoscopy. Conjunctival inflammation, anterior chamber (AC) flare, cells and fibrin, vitreous haze and cells, iridal hyperemia, corneal clouding, lens opacities, and onset times. Intracamerally injected eyes frequently showed conjunctival congestion, AC cells and flare, iridal hyperemia, and fibrin within 6 hours. Up to 80% showed AC cells and flare at 9 hours, and up to 70% showed fibrin at 24 hours. These signs diminished within 48 hours. Fibrin and cells also were seen on the lens surface of most of the eyes. Intravitreally injected eyes showed no signs of inflammation within 24 hours, other than some conjunctival inflammation. After the 24-hour time point, in addition to some conjunctival inflammation, some other signs of inflammation were observed infrequently in the intravitreally injected eyes, including minor vitreous cell reaction in 2 eyes. Although there was 1 dispersive OVD-treated eye with cells and fibrin on the lens capsule at 48 hours, no aqueous cells or flare were seen in the AC of any intravitreally injected eyes at any time during the course of the study. The rabbit intravitreal assay, when limited to

  16. Visualization of residual perfluorocarbon liquid using intravitreal triamcinolone acetonide.

    PubMed

    Hirata, Fumisato; Tamura, Hironori; Ogura, Yuichiro

    2005-01-01

    The visualization of transparent perfluorocarbon liquid (PFCL) using triamcinolone acetonide is described. Intravitreal injection of triamcinolone acetonide enabled visualization of residual PFCL intraoperatively. In addition, it was shown that triamcinolone acetonide could visualize PFCL in an in vitro preparation of balanced salt solution. This in vitro experiment confirmed that triamcinolone acetonide also could be adsorbed by PFCL outside the vitreous. Triamcinolone acetonide was helpful to visualize transparent PFCL both in vivo and in vitro, and may be useful at the end of vitrectomy to completely remove residual PFCL from the eye.

  17. Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion in a Chinese Population.

    PubMed

    Gu, Xiaoya; Yu, Xiaobing; Song, Shuang; Dai, Hong

    2017-01-01

    The aim of this work was to compare the efficacy of intravitreal dexamethasone implant (Ozurdex) and intravitreal ranibizumab (Lucentis) in the treatment of macular edema (ME) caused by retinal vein occlusion (RVO). Thirty-two ME cases treated with Ozurdex and 32 ME cases treated with ranibizumab were enrolled, with 26 central (C)RVO and 6 branch (B)RVO subjects in each group. We compared the results of best-corrected visual acuity (BCVA), central retinal thickness, number of injections, and intraocular pressure (IOP) at 1, 2, 3, and 6 months after injection. BCVA in both groups at each follow-up were significantly increased compared to baseline with no statistical difference between the groups. Ozurdex and ranibizumab successfully reduced CMT at each follow-up. Both CRVO and BRVO patients had significant between-group differences in the mean number of injections. Among the CRVO patients, IOP in the Ozurdex group was significantly increased compared to baseline and the ranibizumab group at 1, 2, and 3 months postinjection. Intravitreal injection of Ozurdex and ranibizumab can effectively control ME secondary to RVO and increase a patient's BCVA. The advantages of Ozurdex are fewer injections and longer efficacy, while the advantages of ranibizumab include fewer side effects. © 2017 S. Karger AG, Basel.

  18. Full thickness macular hole case after intravitreal aflibercept treatment.

    PubMed

    Oshima, Yuji; Apte, Rajendra S; Nakao, Shintaro; Yoshida, Shigeo; Ishibashi, Tatsuro

    2015-03-29

    The pathogenesis of macular hole formation is widely accepted as a tractional force at the vitreo-retinal interface in fovea. We report a case of macular hole after intravitreous aflibercept injection for age-related macular degeneration (AMD) associated with contraction of the retinal pigment epithelium (RPE) at the edge of a fibrovascular pigment epithelial detachment (PED). A 94-year old man with neovascular AMD affecting his left eye accompanied by a fibrovascular PED was examined for severe vision loss. Although RPE tear in his left eye was identified before the first aflibercept intravitreous injection performed in order to treat neovascular AMD, he received three aflibercept injections as induction treatment. After induction treatment, a full thickness macular hole was identified associated with the contracted rolled RPE edge beneath the retina. Macular hole is commonly formed associated with tangential vitreous traction. Current report suggests that rapid contraction of the RPE underneath the retina can be one of the causes of a macular hole, and one of the side effects of anti-VEGF therapy for neovascular AMD.

  19. Optical coherence tomography evaluation of macular edema after intravitreal triamcinolone acetonide in patients with parafoveal telangiectasis.

    PubMed

    Cakir, M; Kapran, Z; Basar, D; Utine, C A; Eroglu, F; Perente, I

    2006-01-01

    Parafoveal telangiectasis (PT) is a developmental or acquired microvascular abnormality of the macula. Leakage of the abnormal parafoveal capillaries leads to macular edema with subsequent decrease in visual acuity. Intravitreal triamcinolone acetonide is recently widely used in the management of intraocular proliferative, edematous, and neovascular diseases. This report presents the evaluation of three cases with PT in whom intravitreal triamcinolone acetonide (IVTA) injection was performed. Fundus fluorescein angiography (FA) and optical coherence tomography (OCT) were used in follow-up of the patients. Following pars plana intravitreal injection of 4 mg of triamcinolone acetonide, the patients had angiographic improvement of the macular edema and minimal decrease in retinal thickness on OCT, accompanied by improvement in visual acuity and subjective visual assessment. The results of the present study on parafoveal capillary telangiectasis suggest that the intravitreal injection of triamcinolone acetonide may be a therapeutic option to increase visual acuity and decrease vascular leakage on FA. Following IVTA procedure, follow-up of these patients with both OCT and FA is important for correct clinical evaluation. Future studies on this method seem to be warranted.

  20. Investigating the movement of intravitreal human serum albumin nanoparticles in the vitreous and retina.

    PubMed

    Kim, Hyuncheol; Robinson, Shaun B; Csaky, Karl G

    2009-02-01

    To investigate the movement of intravitreally injected human serum albumin nanoparticles (HSA-NP) with respect to nanoparticle surface charge and retinal injury. HSA-NPs were developed by a desolvation technique. HSA-NPs were cationized by covalent coupling of hexamethylenediamine on the particle surface. Either anionic or cationic HSA-NPs were injected to determine the effect of surface charge on intravitreal nanoparticle movement. HSA-NPs were injected intravitreally into both normal and laser photocoagulated eyes to examine the effect of the integrity of retinal tissue on the retinal penetration. The retinal penetration of fluorescence labeled anionic HSA-NPs was investigated by confocal microscopy. Anionic particles (-33.3+/-6.1 mV) more easily diffused through the 3-dimensional vitreal network of collagen fibrils than did their cationic counterparts (11.7+/-7.2 mV). In the laser photocoagulated retina, more HSA-NPs were detected in the choroidal space, compared to the normal retina. The immunohistochemical studies indicated that HSA-NPs were taken up into Müller cells. The movement of intravitreal nanoparticles depended on both nanoparticles surface charge and retinal injury. The Müller cells might play an important role in the retinal penetration of nanoparticles. The anionic HSA-NP is a promising drug or gene delivery carrier to the sub-retinal space and RPE.

  1. Evaluation of the effectiveness and safety of glucocorticoids intravitreal implant therapy in macular edema due to retinal vein occlusion.

    PubMed

    Michalska-Małecka, Katarzyna; Gaborek, Aneta; Nowak, Mariusz; Halat, Tomasz; Pawłowska, Mariola; Śpiewak, Dorota

    2016-01-01

    The purpose of this study was to evaluate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and functions in eyes with macular edema (ME) secondary to retinal vein occlusion. Efficacy outcomes of the treatment were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Safety outcomes were intraocular pressure and cornea endothelial cell density. The study was conducted by the prospective analysis on 36 patients (17 women and 19 men) aged 28-77 years (the average age was 58±15 years) treated with the injection of dexamethasone implant because of the persistent ME at the Department of Ophthalmology and Ophthalmology Outpatient Clinic of the University Centre of Ophthalmology and Oncology in Katowice. The studied group included 16 patients with central retinal vein occlusion (16 eyes), and 20 patients with branch retinal vein occlusion (20 eyes). We found a significant increase of BCVA after first, second, and third month of treatment. Six months after the treatment, BCVA decreased, although not significantly compared with the value obtained in the third month. Two months after the intravitreal implantation of dexamethasone delivery system, CRT was 338±163 μm and was significantly lower compared with pretreatment value. Between third and sixth month after the treatment, we found insignificant increase of CRT compared with thickness observed in second month. Two months after the treatment, we found an increase in intraocular pressure in 36% of cases and a further decrease during the final visit 6 months after the treatment. During the treatment, there were no significant differences in endothelial cell density in branch retinal vein occlusion and central retinal vein occlusion. We found the intravitreal dexamethasone implant to be safe, well tolerated, and likely to lead to fast morphological and functional improvement of the macula and visual rehabilitation in patients with ME due to retinal vein occlusion.

  2. Efficient vitreolysis by combining plasmin and sulfur hexafluoride injection in a preclinical study in rabbit eyes

    PubMed Central

    Wu, Wei-Chi; Liu, Chi-Hsien; Chen, Chih-Chun; Wang, Nan-Kai; Chen, Kwan-Jen; Chen, Tun-Lu; Hwang, Yih-Shiou; Li, Lien-Min

    2012-01-01

    Purpose To investigate the efficacy of plasmin and sulfur hexafluoride (SF6) on the vitreoretinal junction, as well as the long-term safety in the eye and effect on the recipient’s general health after application in the eye. Methods The study design included four groups of rabbits with three animals in each group. Group 1 received an intravitreal injection (IVI) of plasmin and SF6 in the right eye; group 2 received an IVI of plasmin in the right eye; group 3 received an IVI of SF6 in the right eye; and group 4 received an IVI of balanced salt solution in the right eye, which served as a normal control. Long-term safety (up to approximately three months) after plasmin and/or SF6 injection was evaluated morphologically by clinical examination, histology, and immunohistochemistry, and functionally by electroretinograms (ERGs). General health evaluations after intravitreal injection included the assessment of weight gain, food intake, body temperature, and complete blood count analysis. Results Plasmin plus SF6 injection resulted in complete posterior vitreous detachment (PVD), whereas plasmin or SF6 injection alone resulted in only partial PVD. Balanced salt solution did not induce PVD. Eighty days after intravitreal injection, there were no major differences among the eyes of the three groups of animals compared with the normal control animals upon clinical evaluation, or regarding retinal morphology and ERGs. The lenses examined remained clear for up to 80 days following the intravitreal injection of plasmin plus SF6, except one eye in the plasmin-treated group. ERGs decreased transiently one week after intravitreal injection in groups 1 through 3, but animals recovered fully to normal status afterward. General health was not affected after the injection of plasmin plus SF6. Conclusions Efficient vitreoretinal separation could be achieved, and an acceptable long-term safety profile was noted after plasmin plus SF6 injection in the eye. No major ocular toxicity or

  3. Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP).

    PubMed

    Konstantinidis, Lazaros; Mameletzi, Evangelia; Mantel, Irmela; Pournaras, Jean-Antoine; Zografos, Leonidas; Ambresin, Aude

    2009-09-01

    Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 microm, and decreased significantly to a mean of 224 microm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 microm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and

  4. Steam-injected gas turbine analysis: Steam rates

    SciTech Connect

    Rice, I.G.

    1995-04-01

    This paper presents an analysis of steam rates in steam-injected gas turbines (simple and reheat). In considering a gas turbine of this type, the steam-injection flow is separated from the main gas stream for analysis. Dalton`s and Avogadro`s laws of partial pressure and gas mixtures are applied. Results obtained provide for the accurate determination of heat input, gas expansion based on partial pressures, and heat-rejection steam-enthalpy points.

  5. Steam-injected gas turbine analysis: steam rates

    NASA Astrophysics Data System (ADS)

    Rice, I. G.

    1995-04-01

    This paper presents an analysis of steam rates in steam-injected gas turbines (simple and reheat). In considering a gas turbine of this type, the steam-injection flow is separated from the main gas stream for analysis. Dalton's and Avogadro's laws of partial pressure and gas mixtures are applied. Results obtained provide for the accurate determination of heat input, gas expansion based on partial pressures, and heat-rejection steam-enthalpy points.

  6. Immobilized Bioluminescent Reagents in Flow Injection Analysis.

    NASA Astrophysics Data System (ADS)

    Nabi, Abdul

    Available from UMI in association with The British Library. Bioluminescent reactions exhibits two important characteristics from an analytical viewpoint; they are selective and highly sensitive. Furthermore, bioluminescent emissions are easily measured with a simple flow-through detector based on a photomultiplier tube and the rapid and reproducible mixing of sample and expensive reagent is best achieved by a flow injection manifold. The two most important bioluminescent systems are the enzyme (luciferase)/substrate (luciferin) combinations extracted from fireflies (Photinus pyralis) and marine bacteria (Virio harveyi) which requires ATP and NAD(P)H respectively as cofactors. Reactions that generate or consume these cofactors can also be coupled to the bioluminescent reaction to provide assays for a wide range of clinically important species. A flow injection manifold for the study of bioluminescent reactions is described, as are procedures for the extraction, purification and immobilization of firefly and bacterial luciferase and oxidoreductase. Results are presented for the determination of ATP using firefly system and the determination of other enzymes and substrates participating in ATP-converting reactions e.g. creatine kinase, ATP-sulphurylase, pyruvate kinase, creatine phosphate, pyrophosphate and phophoenolypyruvate. Similarly results are presented for the determination of NAD(P)H, FMN, FMNH_2 and several dehydrogenases which produce NAD(P)H and their substrates, e.g. alcohol, L-lactate, L-malate, L-glutamate, Glucose-6-phosphate and primary bile acid.

  7. Successful use of intravitreal bevacizumab and pascal laser photocoagulation in the management of adult Coats' disease.

    PubMed

    Raoof, Naz; Quhill, Fahd

    2013-01-01

    Traditional methods of managing exudative retinal detachment secondary to Coats' disease have been associated with varying degrees of success. We describe a case of a 34 year-old male who presented with a sub-total exudative retinal detachment of the right eye that encroached upon the macula, associated with a vasoproliferative tumor secondary to Coats' disease. The patient under-went successful treatment with two intravitreal injections of bevacizumab (Avastin, Genetech Inc., San Francisco, CA, USA) combined with targeted laser photocoagulation with a 532 nm Pascal laser (Topcon Corp., Tokyo, Japan). The visual acuity improved 5 days after the second intravitreal injection from 6/18 to 6/5, with no residual macular edema and complete regression of the vasoproliferative tumor. The improvement in visual acuity was maintained at 12 months post-treatment. We believe this is the first case report describing the successful use of Pascal laser photocoagulation with intravitreal bevacizumab in the treatment of Coats' disease. Our aim was to defer laser treatment until 'near total' retinal reattachment and regression of the vasoproliferative tumor was achieved. There are, however, reports of vitreous fibrosis in patients with Coats' disease treated with intravitreal bevacizumab. This suggests further long-term follow-up studies are required in patients treated with this approach.

  8. Use of Intravitreal Dexamethasone in a Case of Anterior Ischemic Optic Neuropathy.

    PubMed

    Nuzzi, Raffaele; Monteu, Francesca

    2017-01-01

    Nowadays there is no unique and well-established treatment for nonarteritic anterior ischemic optic neuropathy, despite being the main acute pathology that affects the optic nerve in the elderly population and often resulting in a significant loss of visual acuity. The effectiveness of oral steroids is still under debate in the international literature, although many studies show that patients treated with high doses of systemic corticosteroids have a significantly higher chance of improved visual acuity and visual fields. The authors propose an intravitreal dexamethasone injection/implant as initial and acute therapy. Compared to systemic corticosteroids, intravitreal dexamethasone has the advantage of avoiding any systemic side effects of steroids. On the other hand, a rise in intraocular pressure might occur, manageable with local antiglaucoma drugs, especially in patients at risk, and there is a risk of induced cataract. The pharmacodynamics of the intravitreal dexamethasone slow-release implant is characterized by a first step with high release concentrations and a second following phase with decreasing concentrations. Therefore, the use of emergency dexamethasone (high concentration) intravitreal injection is justified as a treatment after the first detection of an ischemic optic anterior neuropathy.

  9. Ocular and systemic toxicity of intravitreal topotecan in rabbits for potential treatment of retinoblastoma.

    PubMed

    Buitrago, Emiliano; Del Sole, María José; Torbidoni, Ana; Fandino, Adriana; Asprea, Marcelo; Croxatto, J O; Chantada, Guillermo L; Bramuglia, Guillermo F; Schaiquevich, Paula

    2013-03-01

    Treatment of intraocular retinoblastoma with vitreous seeding is a challenge. Different routes of chemotherapy administration have been explored in order to attaining pharmacological concentrations into the posterior chamber. Intravitreal drug injection is a promissing route for maximum bioavailability to the vitreous but it requires a well defined dose for achieving tumor control while limited toxicity to the retina. Topotecan proved to be a promising agent for retinoblastoma treatment due to its pharmacological activity and limited toxicity. High and prolonged concentrations were achieved in the rabbit vitreous after 5 μg of intravitreal topotecan. However, whether a lower dose could achieve potentially therapeutic levels remained to be determined. Thus, we here study the pharmacokinetics of topotecan after 0.5 μg and the toxicity profile of intravitreal topotecan in the rabbit eye as a potential treatment of retinoblastoma. A cohort of rabbits was used to study topotecan disposition in the vitreous after a single dose of 0.5 μg of intravitreal topotecan. In addition, an independent cohort of non-tumor bearing rabbits was employed to evaluate the clinical and retinal toxicity after four weekly injections of two different doses of intravitreal topotecan (Group A, 5 μg/dose; Group B, 0.5 μg/dose) to the right eye of each animal. The same volume (0.1 ml) of normal saline was administered to the left eye as control. A third group of rabbits (Group C) served as double control (both eyes injected with normal saline). Animals were weekly evaluated for clinical and hematologic values and ocular evaluations were performed with an inverse ophthalmoscope to establish potential topotecan toxicity. Weekly controls included topotecan quantitation in plasma of all rabbits. Electroretinograms (ERGs) were recorded before and after topotecan doses. One week after the last injection, topotecan concentrations were measured in vitreous of all eyes and samples for retinal

  10. Incidence of Intraocular Pressure Elevation following Intravitreal Ranibizumab (Lucentis) for Age-related Macular Degeneration

    PubMed Central

    Reis, Gustavo MSM; Grigg, John; Chua, Brian; Lee, Anne; Lim, Ridia; Higgins, Ralph; Martins, Alessandra; Goldberg, Ivan

    2017-01-01

    ABSTRACT Aim The aim of this article is to evaluate the rate of patients developing sustained elevated intraocular pressure (IOP) after ranibizumab (Lucentis) intravitreal (IVT) injections. Design This is a retrospective study. Participants Charts of 192 consecutive patients receiving Lucentis for age-related macular degeneration (AMD) were retrospectively reviewed. Materials and methods We enrolled patients with at least two IOP measurements between injections. Elevated IOP was defined as >21 mm Hg with an increase of at least 20% from baseline. Noninjected contralateral eyes of the same patient cohort were used as control. Main outcome measures Primary outcome was defined as elevated IOP. Secondary outcomes were presence and type of glaucoma, number of injections, and time to IOP elevation. Results Elevated IOP occurred at a significantly higher rate in eyes receiving IVT ranibizumab (7.47%; n = 9) compared with control (0.93%; n = 1). Patients with preexisting glaucoma or ocular hypertension (OHT) were more likely to develop elevated IOP after IVT ranibizumab injection. Conclusion Intravitreal ranibizumab injections are associated with sustained IOP elevation in some eyes. How to cite this article Reis GMSM, Grigg J, Chua B, Lee A, Lim R, Higgins R, Martins A, Goldberg I, Clement CI. The Incidence of Intraocular Pressure Elevation following Intravitreal Ranibizumab (Lucentis) for Age-related Macular Degeneration. J Curr Glaucoma Pract 2017;11(1):3-7. PMID:28138211

  11. Pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits

    PubMed Central

    Sinapis, Christos I; Routsias, John G; Sinapis, Angelos I; Sinapis, Dimitrios I; Agrogiannis, George D; Pantopoulou, Alkistis; Theocharis, Stamatis E; Baltatzis, Stefanos; Patsouris, Efstratios; Perrea, Despoina

    2011-01-01

    Purpose: To describe the pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits. Methods: The right eye of 20 rabbits was injected intravitreally with 1.25 mg/0.05 mL bevacizumab. Both eyes of four rabbits each time were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in serum, aqueous humor, and vitreous. Results: Maximum vitreous (406.25 μg/mL) and aqueous humor (5.83 μg/mL) concentrations of bevacizumab in the right eye were measured at day 1. Serum bevacizumab concentration peaked at day 8 (0.413 μg/mL) and declined to 0.032 μg/mL at 4 weeks. Half-life values in right vitreous, right aqueous humor, and serum were 6.61, 6.51, and 5.87 days, respectively. Concentration of bevacizumab in the vitreous of the noninjected eye peaked at day 8 (0.335 ng/mL) and declined to 0.218 ng/mL at 4 weeks. In the aqueous humor of the noninjected eye, maximum concentration of bevacizumab was achieved at day 8 (1.6125 ng/mL) and declined (to 0.11 ng/mL) at 4 weeks. Conclusion: The vitreous half-life of 1.25 mg/0.05 mL intravitreal bevacizumab was 6.61 days in this rabbit model. Maximum concentrations of bevacizumab were reached at day 1 in both vitreous and aqueous humor of the right eye and at day 8 in the serum. Very low concentrations of bevacizumab were measured in the fellow noninjected eye. PMID:21629577

  12. Combined therapy (intravitreal bevacizumab plus verteporfin photodynamic therapy) versus intravitreal bevacizumab monotherapy for choroidal neovascularization due to age-related macular degeneration: a 1-year follow-up study

    PubMed Central

    Saviano, Sandro; Leon, Pia Easter; Mangogna, Alessandro; Tognetto, Daniele

    2016-01-01

    Purpose To assess the efficacy and safety of combined intravitreal bevacizumab and low-fluency-rate photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) and to compare it with intravitreal bevacizumab monotherapy. Methods A total of 62 eyes of 62 patients with angiographic evidence of CNV were divided into 2 groups: the eyes of one group were treated with a combined therapy of 1 intravitreal bevacizumab injection (1.25 mg) and PDT within 7 days; the eyes of the other group received intravitreal bevacizumab monotherapy. Clinical evidence of complications, best-corrected visual acuity (BVCA) and fluorescein leakage were evaluated. Best-corrected visual acuity and optical coherence tomography (OCT) were tested monthly and followed for 12 months. Results In the combined group the mean BCVA increased from 0.61 logMAR before the treatment to 0.54 logMAR at 12 months’ follow-up. In the monotherapy group the mean BCVA increased from 0.65 logMAR to 0.60 logMAR at 12 months’ follow-up. There was no significant difference in visual acuity outcomes between groups (P > 0.05). In the combined group the mean number of treatments was 1.19 per patient; in the monotherapy group, 5.31 per patient (P < 0.01). Conclusions Combined therapy appears to be an effective option for CNV associated with AMD treatment allowing a significant reduction of intravitreal injections. PMID:27582675

  13. Drug injecting and HIV risk among injecting drug users in Hai Phong, Vietnam: a qualitative analysis.

    PubMed

    Ahmed, Tanvir; Long, Thanh Nguyen; Huong, Phan Thi; Stewart, Donald Edwin

    2015-01-29

    Hai Phong, located in northern Vietnam, has become a high HIV prevalence province among Injecting Drug Users (IDUs) since the infection shifted from the southern to the northern region of the country. Previous research indicates high levels of drug and sex related risk behaviour especially among younger IDUs. Our recent qualitative research provides a deeper understanding of HIV risk behaviour and highlights views and experiences of IDUs relating to drug injecting and sharing practices. Fifteen IDUs participated in semi-structured interviews conducted in September-October, 2012. Eligible participants were selected from those recruited in a larger scale behavioural research project and identified through screening questions. Interviews were conducted by two local interviewers in Vietnamese and were audiotaped. Ethical procedures, including informed consent and participants' understanding of their right to skip and withdraw, were applied. Transcripts were translated and double checked. The data were categorised and coded according to themes. Thematic analysis was conducted and a qualitative data analysis thematic framework was used. Qualitative analysis highlighted situational circumstances associated with HIV risks among IDUs in Hai Phong and revealed three primary themes: (i) places for injecting, (ii) injecting drugs in small groups, and (iii) sharing practices. Our results showed that shared use of jointly purchased drugs and group injecting were widespread among IDUs without adequate recognition of these as HIV risk behaviours. Frequent police raids generated a constant fear of arrest. As a consequence, the majority preferred either rail lines or isolated public places for injection, while some injected in their own or a friend's home. Price, a heroin crisis, and strong group norms encouraged collective preparation and group injecting. Risk practices were enhanced by a number of factors: the difficulty in getting new syringes, quick withdrawal management

  14. Early versus delayed intravitreal betamethasone as an adjuvant in the treatment of presumed postoperative endophthalmitis: a randomised trial.

    PubMed

    Koehrer, Philippe; Bron, Alain M; Chiquet, Christophe; Thuret, Gilles; Delbosc, Bernard; Berrod, Jean-Paul; Bourcier, Tristan; Sauer, Arnaud; Jonval, Lysiane; D'Athis, Philippe; Creuzot-Garcher, Catherine

    2016-08-01

    To compare early versus delayed intravitreal betamethasone as an adjuvant in the treatment of presumed acute postoperative endophthalmitis after phacoemulsification. Patients with presumed postcataract surgery endophthalmitis were included in this prospective, randomised, multicentre study. On admission, patients received intravitreal vancomycin and ceftazidime, and were randomly assigned to intravitreal betamethasone injection (early-IVB) group or no immediate injection (delayed-IVB) group. After 48 h, a second intravitreal antibiotic injection associated with intravitreal betamethasone was given to all patients. In patients with severe endophthalmitis or clinical deterioration, a prompt or delayed vitrectomy was performed. The primary outcome was the proportion of patients achieving a visual acuity (VA) of 20/40 or better at 12 months. The secondary outcomes were the rate of delayed vitrectomy and the rate of complications (retinal detachment and phthisis). Ninety-seven eyes of 97 patients were included, 45 in the early-IVB group and 52 in the delayed-IVB group. Overall, 62.9% of patients achieved a VA ≥20/40 at 1 year. There was no statistically significant difference in the visual outcome between the two groups at 1 year, whatever their baseline VA or light perception or hand motion or more (p=0.55 and p=0.10, respectively). The rates of delayed vitrectomy, retinal detachment and phthisis bulbi were not significantly different between the two groups (p=0.42, p=0.37 and p=0.44, respectively). Early intravitreal betamethasone had no clear advantage versus delayed injection in the management of presumed postoperative endophthalmitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

    PubMed Central

    Hunter, Rebecca S; Lobo, Ann-Marie

    2011-01-01

    Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis. PMID:22140307

  16. Identifying heterogeneity among injection drug users: a cluster analysis approach.

    PubMed

    Shaw, Souradet Y; Shah, Lena; Jolly, Ann M; Wylie, John L

    2008-08-01

    We used cluster analysis to subdivide a population of injection drug users and identify previously unknown behavioral heterogeneity within that population. We applied cluster analysis techniques to data collected in a cross-sectional survey of injection drug users in Winnipeg, Manitoba. The clustering variables we used were based on receptive syringe sharing, ethnicity, and types of drugs injected. Seven clusters were identified for both male and female injection drug users. Some relationships previously revealed in our study setting, such as the known relationship between Talwin (pentazocine) and Ritalin (methylphenidate) use, injection in hotels, and hepatitis C virus prevalence, were confirmed through our cluster analysis approach. Also, relationships between drug use and infection risk not previously observed in our study setting were identified, an example being a cluster of female crystal methamphetamine users who exhibited high-risk behaviors but an absence or low prevalence of blood-borne pathogens. Cluster analysis was useful in both confirming relationships previously identified and identifying new ones relevant to public health research and interventions.

  17. TARANTULA HAIR ASSOCIATED PANUVEITIS TREATED WITH SUSTAINED-RELEASE INTRAVITREAL DEXAMETHASONE IMPLANT.

    PubMed

    Morkin, Melina I; Rifkin, Lana M; Dang, Sabin; Baumal, Caroline R

    2017-01-01

    To report a case of tarantula hair-induced panuveitis treated with sustained-release intravitreal dexamethasone implant and followed by sequential spectral domain optical coherence tomography imaging. Findings on clinical examination, anterior segment optical coherence tomography, corneal in vivo confocal microscopy, color fundus photos, fluorescein angiography, and retinal spectral domain optical coherence tomography are presented. Sequential optical coherence tomography images demonstrated the course of the chorioretinal lesions before and after sustained-release intravitreal dexamethasone implant. A 19-year-old female presented with localized temporal episcleritis and scleritis that incompletely resolved despite multiple courses of topical and oral corticosteroids. She subsequently developed focal vitritis and chorioretinitis, and was found to have tarantula hair-induced panuveitis. Anterior segment optical coherence tomography and in vivo confocal microscopy confirmed the presence of tarantula hairs embedded in the anterior corneal stroma. There was only transient improvement with posterior sub-Tenon's Kenalog injection. After treatment with sustained-release intravitreal dexamethasone implant, her symptoms improved and the chorioretinal lesions became inactive. Sequential spectral domain optical coherence tomography images revealed hyperreflective inner retina lesions that progressed to involve the outer retina, and then flattened to near resolution after therapy. This is the first case showing positive clinical outcomes supported by sequential retinal spectral domain optical coherence tomography using a sustained-release intravitreal dexamethasone implant to treat ophthalmia nodosa-induced by tarantula hairs.

  18. Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

    PubMed

    Borke, Tina; Najberg, Mathie; Ilina, Polina; Bhattacharya, Madhushree; Urtti, Arto; Tenhu, Heikki; Hietala, Sami

    2017-08-23

    Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Alternated intra-arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: preliminary successful results without systemic chemotherapy.

    PubMed

    De Francesco, Sonia; Galluzzi, Paolo; Bracco, Sandra; Menicacci, Felice; Motolese, Edoardo; Hadjistilianou, Theodora

    2015-12-01

    To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control.

  20. Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI

    PubMed Central

    Molokhia, Sarah A.; Jeong, Eun-Kee; Higuchi, William I.; Li, S. Kevin

    2008-01-01

    The distribution and clearance of macromolecules in ocular delivery are not well understood. It has been hypothesized that iontophoresis can enhance transscleral delivery of macromolecules. The objective of this study was to investigate the ocular distribution of a macromolecule after transscleral iontophoretic delivery and intravitreal injection in vivo using nuclear magnetic resonance imaging (MRI) and to compare these results. Experiments of constant current transscleral iontophoresis of 4 mA or intravitreal injection were performed on New Zealand white rabbits in vivo. Iontophoresis experiments were also performed on rabbits postmortem. Galbumin™ (Gd-labeled albumin) was the model permeant surrogate to clinical therapeutic agents. MRI was used to monitor the distribution of the molecule in the eye after ocular iontophoresis and intravitreal injection. In addition, the conjunctiva, sclera, choroid, and retina were extracted in the transscleral iontophoresis study to determine the amounts of Galbumin™ in these tissues using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The results show that iontophoresis enhanced the ocular delivery of Galbumin™. The macromolecule was mainly delivered into the conjunctiva and sclera in microgram quantities and then diffused towards the posterior section in the upper hemisphere of the eye in vivo. Both in vivo and postmortem studies show that the iontophoretic delivery of Galbumin™ into the vitreous was below the detection limit. In the intravitreal injection study, the diffusion coefficient of Galbumin™ in the vitreous humor was estimated to be close to that of free aqueous diffusion. PMID:19000673

  1. Micelle formulation of hexadecyloxypropyl-cidofovir (HDP-CDV) as an intravitreal long-lasting delivery system.

    PubMed

    Ma, Feiyan; Nan, Kaihui; Lee, SuNa; Beadle, James R; Hou, Huiyuan; Freeman, William R; Hostetler, Karl Y; Cheng, Lingyun

    2015-01-01

    There still is an unmet need for a safe and sustained intravitreal drug delivery system. In this study we are proposing and characterizing a micelle based, clear-media intravitreal drug delivery system using the lipid derivatized nucleoside analog, hexadecyloxypropyl-cidofovir (HDP-CDV, CMX 001). HDP-CDV forms micelles in water and in vitreous supernatant with the critical micelle concentration of 19 μg/mL and 9 μg/mL, respectively at 37 °C. The formed micelles had the average size of 274.7 nm and the Zeta potential of -47.1 mV. Drug release study in the excised rabbit vitreous showed a sustained release profile with a half-life of 2.7 days. The micelle formulation of HDP-CDV demonstrated a good safety profile in two animal species (rabbit and guinea pig) following intravitreal injection. The sustained efficacy was tested in a pretreatment study design and the drug potency was tested in an ongoing herpes simplex virus (HSV-1) retinitis model. The pretreatment studies using single intravitreal injection and later HSV-1 infection revealed at least 9 weeks of vitreous presence and therapeutic level of HDP-CDV, with 71% eyes protection from infection. The treatment study demonstrated that intravitreal administration halted active HSV-1 retinitis in 80% of the infected eyes while cidofovir (CDV) treatment failed to suppress active HSV-1 retinitis. In summary, lipid derivatized nucleoside analogs can be formulated as a micelle intravitreal injection and provides a sustained drug release in vitreous for chronic retinal diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Pharmacokinetics, Safety, and Efficacy of Intravitreal Digoxin in Preclinical Models for Retinoblastoma.

    PubMed

    Winter, Ursula; Buitrago, Emiliano; Mena, Hebe A; Del Sole, Maria José; Laurent, Viviana; Negrotto, Soledad; Francis, Jasmine; Arana, Eloisa; Sgroi, Mariana; Croxatto, Juan O; Djaballah, Hakim; Chantada, Guillermo L; Abramson, David; Schaiquevich, Paula

    2015-07-01

    To assess in vitro cytotoxic activity and antiangiogenic effect, ocular and systemic disposition, and toxicity of digoxin in rabbits after intravitreal injection as a potential candidate for retinoblastoma treatment. A panel of two retinoblastoma and three endothelial cell types were exposed to increasing concentrations of digoxin in a conventional (72-hour exposure) and metronomic (daily exposure) treatment scheme. Cytotoxicity was defined as the digoxin concentration that killed 50% of the cells (IC50) and was assessed with a vital dye in all cell types. Induction of apoptosis and cell-cycle status were evaluated by flow cytometry after both treatment schemes. Ocular and systemic disposition after intravitreal injection as well as toxicity was assessed in rabbits. Electroretinograms (ERGs) were recorded before and after digoxin doses and histopathological examinations were performed after enucleation. Digoxin was cytotoxic to retinoblastoma and endothelial cells under conventional and metronomic treatment. IC50 was comparable between both schedules and induced apoptosis in all cell lines. Calculated vitreous digoxin Cmax was 8.5 μg/mL and the levels remained above the IC50 for at least 24 hours after intravitreal injection. Plasma digoxin concentration was below 0.5 ng/ml. Retinal toxicity was evident after the third intravitreal dose with considerable changes in the ERG and histologic damage to the retina. Digoxin has antitumor activity for retinoblastoma while exerting antiangiogenic activity in vitro at similar concentrations. Metronomic treatment showed no advantage in terms of dose for cytotoxic effect. Four biweekly injections of digoxin led to local toxicity to the retina but no systemic toxicity in rabbits.

  3. Early change of central macular thickness after intravitreous triamcinolone or bevacizumab in diabetic macular edema or retinal vein occlusion.

    PubMed

    Sonoda, Yasushi; Arimura, Noboru; Shimura, Masahiko; Sakamoto, Taiji

    2011-02-01

    To evaluate the immediate changes after intravitreous triamcinolone acetonide or intravitreous bevacizumab in diabetic macular edema (DME). A nonrandomized interventional study. Type 2 diabetic patients were included. Intravitreous triamcinolone acetonide (4 mg) was injected for 22 eyes with DME and IVB (1.25 mg) for 18 eyes with DME. The early time-dependent changes of central macular thickness were evaluated by optical coherence tomography before and from 1 hour to 1 month after intervention. Intravitreous bevacizumab was also tested in patients with retinal vein occlusion as a control of non-DME. Visual acuity was also examined. Compared with the baseline, central macular thickness of eyes with DME decreased significantly 1 hour after intravitreous triamcinolone acetonide (P < 0.05, Wilcoxon signed rank test), while it did not significantly until 24 hours after IVB. The decrease in central macular thickness was observed significantly from 3 hours after IVB in retinal vein occlusion (P < 0.05, Wilcoxon signed rank test), and it was more evident in retinal vein occlusion than DME after IVB. Visual acuity improved significantly in DME with intravitreous triamcinolone acetonide or IVB at 1 month (P < 0.01 and P < 0.05, respectively, Wilcoxon signed rank test). Factors responsive to triamcinolone acetonide, other than vascular endothelial growth factor, might play an important role in pathogenesis of DME compared with retinal vein occlusion. Although no conclusion can be drawn, immediate decrease in central macular thickness after intravitreous triamcinolone acetonide might indicate the possible involvement of a nongenomic pathway of triamcinolone acetonide action.

  4. Status of NINJA: the Numerical INJection Analysis project

    NASA Astrophysics Data System (ADS)

    Cadonati, Laura; Aylott, Benjamin; Baker, John G.; Boggs, William D.; Boyle, Michael; Brady, Patrick R.; Brown, Duncan A.; Brügmann, Bernd; Buchman, Luisa T.; Buonanno, Alessandra; Camp, Jordan; Campanelli, Manuela; Centrella, Joan; Chatterji, Shourov; Christensen, Nelson; Chu, Tony; Diener, Peter; Dorband, Nils; Etienne, Zachariah B.; Faber, Joshua; Fairhurst, Stephen; Farr, Benjamin; Fischetti, Sebastian; Guidi, Gianluca; Goggin, Lisa M.; Hannam, Mark; Herrmann, Frank; Hinder, Ian; Husa, Sascha; Kalogera, Vicky; Keppel, Drew; Kidder, Lawrence E.; Kelly, Bernard J.; Krishnan, Badri; Laguna, Pablo; Lousto, Carlos O.; Mandel, Ilya; Marronetti, Pedro; Matzner, Richard; McWilliams, Sean T.; Matthews, Keith D.; Mercer, R. Adam; Mohapatra, Satyanarayan R. P.; Mroué, Abdul H.; Nakano, Hiroyuki; Ochsner, Evan; Pan, Yi; Pekowsky, Larne; Pfeiffer, Harald P.; Pollney, Denis; Pretorius, Frans; Raymond, Vivien; Reisswig, Christian; Rezzolla, Luciano; Rinne, Oliver; Robinson, Craig; Röver, Christian; Santamaría, Lucía; Sathyaprakash, Bangalore; Scheel, Mark A.; Schnetter, Erik; Seiler, Jennifer; Shapiro, Stuart L.; Shoemaker, Deirdre; Sperhake, Ulrich; Stroeer, Alexander; Sturani, Riccardo; Tichy, Wolfgang; Liu, Yuk Tung; van der Sluys, Marc; van Meter, James R.; Vaulin, Ruslan; Vecchio, Alberto; Veitch, John; Viceré, Andrea; Whelan, John T.; Zlochower, Yosef

    2009-06-01

    The 2008 NRDA conference introduced the Numerical INJection Analysis project (NINJA), a new collaborative effort between the numerical relativity community and the data analysis community. NINJA focuses on modeling and searching for gravitational wave signatures from the coalescence of binary system of compact objects. We review the scope of this collaboration and the components of the first NINJA project, where numerical relativity groups, shared waveforms and data analysis teams applied various techniques to detect them when embedded in colored Gaussian noise.

  5. Photodynamic Therapy and Intravitreal Bevacizumab with Versus without Triamcinolone for Neovascular Age-related Macular Degeneration; a Randomized Clinical Trial

    PubMed Central

    Piri, Niloofar; Ahmadieh, Hamid; Taei, Ramin; Soheilian, Masoud; Karkhaneh, Reza; Lashay, Alireza; Golbafian, Faegheh; Yaseri, Mehdi; Riazi-Esfahani, Mohammad

    2014-01-01

    Purpose: To compare the outcomes of photodynamic therapy (PDT) combined with intravitreal bevacizumab (IVB) with versus without intravitreal triamcinolone (IVT) in neovascular age-related macular degeneration (AMD). Methods: Eighty-four eyes with active CNV secondary to AMD with no prior treatment were enrolled and followed for 1-year. Eligible eyes were randomly assigned to either PDT/IVB or PDT/IVB/IVT. The main outcome measure was change in best-corrected visual acuity (BCVA). Results: Mean patient age was 71 ± 9 years. BCVA changes from baseline were statistically significant in both study arms at all follow-up intervals, however no significant difference was observed between the two groups regarding BCVA changes at week 12 (95% CI:-0.11–0.12 LogMAR) and other time points (all P > 0.6). Mixed model analysis revealed a significant effect from age (P < 0.001), pigment epithelial detachment (P = 0.009) and baseline BCVA (P < 0.001) on visual improvement. Significant central macular thickness (CMT) reduction occurred at all-time points as compared to baseline in both groups which was comparable between the study arms. There was no significant difference between the study arms in terms of retreatment rate (P = 0.1) and survival to the first repeat IVB injection (P = 0.065). Conclusion: Additional low-dose IVT to a PDT/IVB regimen for neovascular AMD provided no beneficial effects in terms BCVA or CMT, yet demonstrated a trend toward extending the injection-free period. PMID:25709773

  6. Immobilized enzymes in flow-injection analysis: present and trends.

    PubMed

    Ruz, J; Lázaro, F; de Castro, M D

    1988-01-01

    An overview of the use of immobilized enzymes in flow-injection analysis (FIA) is presented. The joint use of FIA and immobilized enzymes means that analytical procedures are easily automated, analytical costs are reduced and methods are faster. The future possibilities for this combination are discussed.

  7. Immobilized enzymes in flow-injection analysis: present and trends

    PubMed Central

    Ruz, J.; Lázaro, F.; de Castro, M. D. Luque

    1988-01-01

    An overview of the use of immobilized enzymes in flow-injection analysis (FIA) is presented. The joint use of FIA and immobilized enzymes means that analytical procedures are easily automated, analytical costs are reduced and methods are faster. The future possibilities for this combination are discussed. PMID:18925183

  8. Determination of Reaction Stoichiometries by Flow Injection Analysis.

    ERIC Educational Resources Information Center

    Rios, Angel; And Others

    1986-01-01

    Describes a method of flow injection analysis intended for calculation of complex-formation and redox reaction stoichiometries based on a closed-loop configuration. The technique is suitable for use in undergraduate laboratories. Information is provided for equipment, materials, procedures, and sample results. (JM)

  9. ANALYSIS OF VOLATILES AND SEMIVOLATILES BY DIRECT AQUEOUS INJECTION

    EPA Science Inventory

    Direct aqueous injection analysis (DAI) with gas chromatographic separation and ion trap mass spectral detection was used to analyze aqueous samples for g/L levels of 54 volatile and semivolatile compounds, and problematic non-purgeables and non-extractables. The method reduces ...

  10. Intravitreal bevacizumab for persistent macular edema with proliferative diabetic retinopathy.

    PubMed

    Gulkilik, Gokhan; Taskapili, Muhittin; Kocabora, Selim; Muftuoglu, Gulipek; Demirci, Goktug

    2010-12-01

    To evaluate the effectiveness of an intravitreal bevacizumab injection on retinal neovascularization and diabetic macular edema (DME) refractory to laser photocoagulation therapy. Thirty-four eyes of 22 patients with proliferative diabetic retinopathy and DME refractory to laser photocoagulation therapy received an intravitreal injection of 1.25 mg/0.05 ml of bevazicumab. Changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), regression of neovascularization over time, and correlation between BCVA and CMT were evaluated. Follow-up visits were at weeks 1, 2 and 4 and months 3 and 6. Mean BCVA was significantly better than baseline only at week 2 (P = 0.036). Mean CMT decreased significantly from baseline at weeks 1, 2, and 4 (P = 0.001). At months 3 and 6, mean CMT increased, albeit insignificantly (P = 0.804 and P = 1.0). The decrease in fluorescein leakage was moderate in all eyes at the end of week 1. At week 2, there was total resolution of fluorescein leakage in 24 (70.5%) eyes and moderate resolution in 10 (29.5%) eyes. At the end of month 3, the fluorescein leakage was fully resolved in 5 (14.7%) eyes, moderately resolved in 24 (70.5%) eyes, and was similar to baseline in 5 (14.7%) eyes. At month 6, the fluorescein leakage was fully resolved in 3 (8.8%) eyes, moderately resolved in 20 (58.8%) eyes, and was similar to baseline in 11 (32.4%) eyes. A moderate but insignificant negative correlation was found between visual acuity and CMT (P > 0.05). Persistence or recurrence of neovascular tissue after panretinal photocoagulation may be attributed to the production of vascular endothelial growth factor by the residual ischemic retina, which also results in persistent or recurrent DME despite macular grid photocoagulation.

  11. Dexamethasone intravitreal implants for diabetic macular edema refractory to ranibizumab monotherapy or combination therapy.

    PubMed

    Gutiérrez-Benítez, L; Millan, E; Arias, L; Garcia, P; Cobos, E; Caminal, M

    2015-10-01

    To determine the effectiveness and local safety of dexamethasone intravitreal implants as a treatment in diabetic macular edema (DME) refractory to intravitreal injections of ranibizumab monotherapy or combination therapy. A retrospective study conducted on patients with DME refractory to ranibizumab monotherapy or combined with other treatments treated with dexamethasone intravitreal implants. The parameters analyzed were visual acuity (VA) by ETDRS (Early Treatment Diabetic Retinopathy Study) charts and foveal thickness by spectral-domain optical coherence tomography (SD-OCT) before the treatment, 2 months after treatment, and at the end of the follow-up. A total of 14 eyes of 14 patients were included, with a mean age of 64 years (SD: 9.5; range 41-78) and a mean follow-up of 7.6 months. The mean VA improved from 53 letters to 59 letters at 2 months (P=.03), and 57 at the end of the follow-up period (P=.3). The mean foveal thickness decreased from 502 μ to 304 μ at 2 months (P=.001), and 376 μ at the end of the follow-up period (P=.009). Further treatment with intravitreal dexamethasone was required in 43% of the patients, and 21% had increased intraocular pressure, which was controlled with topical medication. Intravitreal dexamethasone implant is an effective and locally safe treatment for the management of DME refractory to ranibizumab monotherapy or combined with other treatments. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Intravitreal bevacizumab for macular edema secondary to branch retinal vein occlusion.

    PubMed

    Ehlers, Justis P; Decroos, Francis Char; Fekrat, Sharon

    2011-10-01

    To evaluate the effect of intravitreal bevacizumab on the visual and anatomical outcome in eyes with macular edema secondary to branch retinal vein occlusion. A retrospective, consecutive case series identified 53 consecutive patients with a branch retinal vein occlusion treated with intravitreal bevacizumab. Clinical variables were analyzed, including best-corrected visual acuity, angiographic characteristics, central foveal thickness, and complications. Fifty-three eyes were identified with a mean initial best-corrected visual acuity of 20/137 and final best-corrected visual acuity of 20/96 (P = 0.05). The mean final line change was +1.6 lines (95% confidence interval, +0.7 to +2.3; +8 letters [95% confidence interval, +3.5 to 11.5]). At final follow-up, 28% gained ≥ 3 lines, whereas a loss of >3 lines was seen in 6% of eyes. The mean initial central foveal thickness of 425 μm decreased to 289 μm (P < 0.001). Mean number of injections was 2.5, and mean follow-up was 9 months. Eyes treated for ≤ 6 months after the onset of branch retinal vein occlusion showed improved functional outcomes (e.g., final best-corrected visual acuity, mean line change) as compared with those treated with >6 months of symptoms (P < 0.01). Intravitreal bevacizumab appears to be an effective treatment for macular edema secondary to branch retinal vein occlusion in many subjects. Eyes treated with intravitreal bevacizumab showed a significant reduction in central foveal thickness and improvement in visual acuity. Early treatment with intravitreal bevacizumab resulted in a greater improvement in visual acuity compared with delayed treatment.

  13. Comprehensive Quantitative Analysis of SQ Injection Using Multiple Chromatographic Technologies.

    PubMed

    Chau, Siu-Leung; Huang, Zhi-Bing; Song, Yan-Gang; Yue, Rui-Qi; Ho, Alan; Lin, Chao-Zhan; Huang, Wen-Hua; Han, Quan-Bin

    2016-08-19

    Quality control of Chinese medicine injections remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the best-selling injections, Shenqi Fuzheng (SQ) injection (SQI), via a full component quantitative analysis. A total of 15 representative small molecular components of SQI were simultaneously determined using ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole tandem time-of-flight mass spectrometry (Q-TOF-MS); saccharide composition of SQI was also quantitatively determined by high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) on an amino column before and after acid hydrolysis. The existence of polysaccharides was also examined on a gel permeation chromatography column. The method was well validated in terms of linearity, sensitivity, precision, accuracy and stability, and was successfully applied to analyze 13 SQI samples. The results demonstrate that up to 94.69% (w/w) of this injection product are quantitatively determined, in which small molecules and monosaccharide/sucrose account for 0.18%-0.21%, and 53.49%-58.2%, respectively. The quantitative information contributes to accumulating scientific evidence to better understand the therapy efficacy and safety of complex Chinese medicine injections.

  14. Intravitreal Topotecan Inhibits Laser-induced Choroidal Neovascularization in a Rat Model

    PubMed Central

    Gholipour, Mohammad Ali; Kanavi, Mozhgan Rezaei; Ahmadieh, Hamid; Aldavood, Seyed Javid; Nourinia, Ramin; Hosseini, Seyed Bagher; Daftarian, Narsis; Nashtaei, Ebrahim Mohammad; Tousi, Adib; Safi, Sare

    2015-01-01

    Purpose: A two-phase preclinical study was designed to determine the safe dose of intravitreal topotecan and its inhibitory effect on experimental choroidal neovascularization (CNV) in a rat model. Methods: In phase I, 42 rats were categorized into 6 groups, 5 of which received intravitreal topotecan injections of 0.125 μg, 0.25 μg, 0.5 μg, 0.75 μg, and 1.0 μg/5 μl, respectively; the control group received an injection of normal saline. Ophthalmic examination and electroretinography (ERG) were performed on days 7 and 28, and enucleated globes were processed for histopathology and immunostaining for glial fibrillary acidic protein. In phase II, CNV was induced via laser burns in 20 rats and the animals were divided into 2 groups. One group received topotecan and the other received normal saline intravitreally. Four weeks later, mean scores of fluorescein leakage on fluorescein angiography as well as mean CNV areas on histology sections were compared. Results: In phase I, clinical, ERG and histopathologic results were unremarkable in terms of retinal toxicity in all groups. Based on the results of phase I, a dose of 1 μg/5 μl topotecan was chosen for phase II. Leakage scores obtained from late-phase fluorescein angiography were significantly lower in topotecan-treated than control eyes (P < 0.01) four weeks after induction of CNV. Compared to control eyes, topotecan-treated eyes showed a significantly lower incidence of fibrovascular proliferation (8.7% vs. 96.2%) and significantly smaller areas of CNV (P < 0.01). Conclusion: Intravitreal injection of topotecan at a dose of 1 μg/5 μl is safe and may be a promising treatment for CNV. PMID:26730316

  15. Intravitreal aflibercept for the treatment of choroidal neovascularization associated with pathologic myopia: a pilot study

    PubMed Central

    Korol, Andrii R; Zadorozhnyy, Oleg S; Naumenko, Volodymyr O; Kustryn, Taras B; Pasyechnikova, Nataliya V

    2016-01-01

    Purpose To determine the efficacy of intravitreal aflibercept injections for the treatment of patients with choroidal neovascularization (CNV) associated with pathologic myopia. Methods In this uncontrolled, prospective cohort study, 31 eyes of 30 consecutive patients affected by CNV associated with pathologic myopia were treated with intravitreal aflibercept (2 mg) as needed following two initial monthly doses and observed over a 12-month follow-up period. The primary endpoint was change in best-corrected visual acuity (BCVA) at month 12, while central retinal thickness (CRT) on optical coherence tomography (OCT), neovascularization activity on fluorescein angiography, the number of aflibercept injections administered, and safety were examined as secondary endpoints. Results Patients received a mean of 2.6 intravitreal aflibercept injections over the 12-month study period. Compared with baseline, BCVA improved significantly at all time points (P<0.05). Mean (standard deviation [SD]) decimal BCVA was 0.2 (0.1) at baseline and 0.35 (0.16) at month 12. The greatest improvement in BCVA was seen within the first 2 months (P=0.01). Mean (SD) CRT on OCT decreased from 285 (62) µm at baseline to 227 (42) µm (P=0.01) at month 12. There was a continuous decrease in mean CRT on OCT over time. No cases of endophthalmitis, uveitis, stroke, or retinal detachment were noted. No patient demonstrated an intraocular pressure >20 mmHg during any study visit. Conclusion The 12-month results of intravitreal aflibercept for myopic CNV using an as-needed regimen were positive, showing benefits in visual and anatomic outcomes and an acceptable tolerability profile. PMID:27853350

  16. Comparison of the efficacy of anti-VEGF monotherapy versus PDT and intravitreal anti-VEGF combination treatment in AMD: a Meta-analysis and systematic review

    PubMed Central

    Tong, Yao; Zhao, Ke-Ke; Feng, Dong; Biswal, Manas; Zhao, Pei-Quan; Wang, Zhao-Yang; Zhang, Yun

    2016-01-01

    AIM To compare the effect of anti-vascular endothelial growth factor (VEGF) monotherapy versus photodynamic therapy (PDT) and anti-VEGF combination treatment in age-related macular degeneration (AMD). METHODS A computerized online search was performed using PubMed, Web of Science and the Cochrane Library. Studies that compared anti-VEGF monotherapy with PDT and anti-VEGF combination treatment of AMD and were designed as randomized controlled trials were included. The means and standard deviations of the best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of treatments and proportions of patients who gained BCVA ≥15, 10, 5, or 0 letters at 12th month were extracted. A systematic review and Meta-analysis of the comparison of the two approaches was conducted using Review Manager 5.2. Subgroup. A sensitivity analysis was also performed. RESULTS Eight studies were included. When the subgroup and sensitivity analysis was conducted, the results indicated that in the findings that included the monotherapy group and PDT (standard fluence, SF) group of Kaiser's study, the patients in the monotherapy group had a better BCVA compared with the combination group at 12th month in the PDT (SF) subgroup [weighted mean difference (WMD): 3.54; 95%CI: 0.36 to 6.73; P=0.03], and there were more patients who gained ≥15 letters of BCVA in the monotherapy group compared with the combination group in the total result [odds ratio (OR): 1.41; 95%CI: 1.02 to 1.95; P=0.04]. The same conclusion was obtained in the total result that included the monotherapy group and PDT (reduced fluence, RF) group of Kaiser's study (OR: 1.56; 95%CI: 1.13 to 2.15; P=0.007). However, there were no significant differences in the other indexes between the two therapies. CONCLUSION We found that anti-VEGF monotherapy is more effective on the recovery of visual acuity than combination therapy and more researches with lager sample size should be performed to study on the effect of the two

  17. Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment().

    PubMed

    Witkin, Andre J; Rayess, Nadim; Garg, Sunir J; Maguire, Joseph I; Storey, Philip; Kaiser, Richard S; Hsu, Jason; Vander, James F; Ho, Allen C

    2017-01-01

    To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Retrospective, consecutive, interventional case series. Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455 µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p < 0.001), and mean CFT decreased to 387 µm (p = 0.029). In patients with PED, there was a mean 27.9% reduction in height (p = 0.046) at eight weeks' follow-up. Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.

  18. Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration

    PubMed Central

    Michalska-Małecka, Katarzyna; Kabiesz, Adam; Kimsa, Malgorzata W; Strzałka-Mrozik, Barbara; Formińska-Kapuścik, Maria; Nita, Malgorzata; Mazurek, Urszula

    2016-01-01

    The purpose of this study was to evaluate the systemic effects of intravitreal ranibizumab (Lucentis) treatment in patients with neovascular age-related macular degeneration (AMD). The impact of intravitreal ranibizumab injections on central retinal thickness (CRT) of treated and contralateral untreated eyes, and differences in gene expression patterns in the peripheral blood mononuclear cells were analyzed. The study included 29 patients aged 50 years old and over with diagnosed neovascular AMD. The treatment was defined as 0.5 mg of ranibizumab injected intravitreally in the form of one injection every month during the period of 3 months. CRT was measured by optical coherence tomography. The gene expression profile was assigned using oligonucleotide microarrays of Affymetrix HG-U133A. Studies have shown that there was a change of CRT between treated and untreated eyes, and there were differences in CRT at baseline and after 1, 2, and 3 months of ranibizumab treatment. Three months after intravitreal injection, mean CRT was reduced in the treated eyes from 331.97±123.62 to 254.31±58.75 μm, while mean CRT in the untreated fellow eyes reduced from 251.07±40.29 to 235.45±36.21 μm at the same time. Furthermore, the research has shown that among all transcripts, 3,097 expresses change after the ranibizumab treatment in relation to controls. Among these transcripts, 1,339 were up-regulated, whereas 1,758 were down-regulated. Our results show the potential systemic effects of anti-VEGF therapy for AMD. Moreover, our study indicated different gene expression in peripheral blood mononuclear cells before and after intravitreal ranibizumab treatment. PMID:27069359

  19. Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration.

    PubMed

    Michalska-Małecka, Katarzyna; Kabiesz, Adam; Kimsa, Malgorzata W; Strzałka-Mrozik, Barbara; Formińska-Kapuścik, Maria; Nita, Malgorzata; Mazurek, Urszula

    2016-01-01

    The purpose of this study was to evaluate the systemic effects of intravitreal ranibizumab (Lucentis) treatment in patients with neovascular age-related macular degeneration (AMD). The impact of intravitreal ranibizumab injections on central retinal thickness (CRT) of treated and contralateral untreated eyes, and differences in gene expression patterns in the peripheral blood mononuclear cells were analyzed. The study included 29 patients aged 50 years old and over with diagnosed neovascular AMD. The treatment was defined as 0.5 mg of ranibizumab injected intravitreally in the form of one injection every month during the period of 3 months. CRT was measured by optical coherence tomography. The gene expression profile was assigned using oligonucleotide microarrays of Affymetrix HG-U133A. Studies have shown that there was a change of CRT between treated and untreated eyes, and there were differences in CRT at baseline and after 1, 2, and 3 months of ranibizumab treatment. Three months after intravitreal injection, mean CRT was reduced in the treated eyes from 331.97±123.62 to 254.31±58.75 μm, while mean CRT in the untreated fellow eyes reduced from 251.07±40.29 to 235.45±36.21 μm at the same time. Furthermore, the research has shown that among all transcripts, 3,097 expresses change after the ranibizumab treatment in relation to controls. Among these transcripts, 1,339 were up-regulated, whereas 1,758 were down-regulated. Our results show the potential systemic effects of anti-VEGF therapy for AMD. Moreover, our study indicated different gene expression in peripheral blood mononuclear cells before and after intravitreal ranibizumab treatment.

  20. Effect of photodynamic therapy alone or combined with posterior subtenon triamcinolone acetonide or intravitreal bevacizumab on choroidal hypofluorescence by indocyanine green angiography.

    PubMed

    Hatta, Yoshiyuki; Ishikawa, Kohei; Nishihara, Hiroaki; Ozawa, Shinsuke; Ito, Yasuki; Terasaki, Hiroko

    2010-03-01

    Choroidal hypofluorescence has been reported beneath the photodynamic therapy (PDT) site in clinical studies. We evaluated the choroidal hypofluorescence after combined PDT with posterior subtenon injection of triamcinolone acetonide or PDT with an intravitreal injection of bevacizumab for age-related macular degeneration. Two hundred and forty-two eyes with a subfoveal choroidal neovascularization caused by age-related macular degeneration were studied. Ninety-two eyes underwent PDT alone, 90 eyes underwent PDT with sub-Tenon injection of triamcinolone acetonide, and 60 eyes underwent PDT with intravitreal injection of bevacizumab. Verteporfin-induced choroidal hypoperfusion was determined by indocyanine green angiograms. The intensity of the diffuse fluorescence within the PDT site away from the choroidal neovascularization lesion and from the normal retina just peripheral to the optic disk was measured by densitometry (Topcon IMAGEnet computer system, Topcon, Tokyo, Japan) in the indocyanine green angiogram images obtained at 10 minutes 3 months after the PDT. The ratio of the average brightness of the retina within the PDT area to that of the retina peripheral to the optic disk (irradiated/nonirradiated retinal brightness ratio) was calculated for each angiogram. The irradiated/nonirradiated retinal brightness ratio of the angiograms was 0.96 in the PDT-alone group, 0.85 in the sub-Tenon injection of triamcinolone acetonide-PDT group, and 0.89 in the intravitreal injection of bevacizumab-PDT group (Kruskal-Wallis H test, P < 0.05). The degree of choroidal hypofluorescence in the indocyanine green angiogram images 3 months after PDT in the sub-Tenon injection of triamcinolone acetonide and intravitreal injection of bevacizumab group was higher than that of PDT-alone group. Sub-Tenon injection of triamcinolone acetonide and intravitreal injection of bevacizumab can prolong the duration of the choroidal hypofluorescence after PDT.

  1. Visual Performance in Patients with Neovascular Age-Related Macular Degeneration Undergoing Treatment with Intravitreal Ranibizumab

    PubMed Central

    Loughman, James; Nolan, John M.; Stack, Jim; Pesudovs, Konrad; Meagher, Katherine A.; Beatty, Stephen

    2013-01-01

    Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P < 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition. PMID:23533703

  2. Diffuse diabetic macular oedema treated by intravitreal triamcinolone acetonide: a comparative, non-randomised study

    PubMed Central

    Jonas, J B; Akkoyun, I; Kreissig, I; Degenring, R F

    2005-01-01

    Aim: To report on visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide for treatment of diffuse diabetic macular oedema. Methods: Prospective, comparative, non-randomised clinical interventional study included 136 patients with diffuse diabetic macular oedema. Patients of the study group (97 eyes) received an intravitreal injection of 20–25 mg of triamcinolone acetonide and no other retinal treatment. Patients of the control group (69 eyes) received focal or panretinal laser treatment if indicated. Mean (standard deviation) follow up was 8.4 (SD 6.0) months (range 1.03–25.2 months). Results: Visual acuity (VA) increased significantly (p<0.001) in the study group with 66 (68%) eyes gaining in VA by at least two Snellen lines. In the control group, VA did not change significantly during the first 4 months of follow up, and decreased significantly (p<0.001) towards the end of the follow up. Difference in change of best VA was significant (p<0.001) between both groups. Correspondingly, the number of patients with VA improvement of two or more Snellen lines and visual loss of two or more Snellen lines, respectively, was significantly (p<0.001) higher and lower, respectively, in the study group. Conclusions: Intravitreal triamcinolone acetonide can temporarily increase VA in some patients with diffuse diabetic macular oedema. PMID:15722313

  3. Visual performance in patients with neovascular age-related macular degeneration undergoing treatment with intravitreal ranibizumab.

    PubMed

    Sabour-Pickett, Sarah; Loughman, James; Nolan, John M; Stack, Jim; Pesudovs, Konrad; Meagher, Katherine A; Beatty, Stephen

    2013-01-01

    Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P < 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.

  4. Treatment of recent onset central retinal vein occlusion with intravitreal tissue plasminogen activator: a pilot study

    PubMed Central

    Glacet-Bernard, A.; Kuhn, D.; Vine, A.; Oubraham, H.; Coscas, G.; Soubrane, G.

    2000-01-01

    AIMS—To study the effects of intravitreal tissue plasminogen activator (tPA) in recent onset central retinal vein occlusion (CRVO).
METHODS—15 patients with recent onset CRVO (from 1-21 days' duration, mean 8 days) were given 75-100 µg of tPA intravitreally associate with low dose low molecular weight heparin. CRVO was perfused in nine patients and with mild ischaemia not exceeding 100 disc diameters in six patients. Follow up ranged from 5 to 21 months for 14 patients (mean 8 months). Visual acuity measurement, macular threshold (Humphrey perimeter), fluorescein angiography with the scanning laser ophthalmoscope with special emphasis on retinal circulation times, and retinal perfusion were performed at days 0, 1, and 8 and months 1, 3, and 6.
RESULTS—Visual acuity was significantly improved on the first day after treatment in only one eye, and decreased transiently in six eyes (40%). Retinal blood velocity was not significantly modified by tPA injection. Retinal ischaemia developed in six eyes (43%), leading to panretinal photocoagulation in five eyes including one with rubeosis iridis. At the end of follow up, visual acuity had improved to 20/30 or better in five eyes (36%), including two with complete recovery; visual acuity was worse than 20/200 in three eyes (28%). No complication of tPA injection was observed.
CONCLUSION—Intravitreal tPA treatment for CRVO appears to be simple and safe, but did not significantly modify the course of the occlusion in our patients immediately after treatment. Final visual outcome did not differ significantly from that observed in the natural course of the disease, but final visual acuity seemed to be slightly better. A randomised study is required to determine if intravitreal tPA actually improves visual outcome in CRVO.

 PMID:10837386

  5. In vitro benzyl alcohol cytotoxicity: implications for intravitreal use of triamcinolone acetonide.

    PubMed

    Chang, Yi-Sheng; Wu, Chao-Liang; Tseng, Sung-Huei; Kuo, Pao-Ying; Tseng, Shih-Ya

    2008-06-01

    The aim of the study was to investigate the toxicity of benzyl alcohol (BA), the preservative in commercial triamcinolone acetonide (TA) suspensions, on retinal pigment epithelial (RPE) cells. Cultured RPE cells from a human cell line (ARPE-19) and from rabbits were exposed to the balanced salt solution (control) or BA (0.0225, 0.225, 0.9, 3 or 9mg/mL) for 5, 30, 60, or 120min. Morphological changes of RPE cells were evaluated by the trypan blue in situ staining. The proportions of dead cells were quantitatively measured by the trypan blue exclusion assay, and those of functional cells were assessed by a mitochondrial dehydrogenase assay. The mechanism of cytotoxicity was determined by the acridine orange/ethidium bromide staining and DNA laddering technique. Furthermore, ultrastructural changes were observed by transmission electron microscopy. The results showed that RPE cell damage was dose- and time-dependent. BA 0.225mg/mL, the clinically relevant concentration in TA following intravitreal injection, caused ultrastructural damage and impaired human RPE cell function at 2h; but BA 0.0225mg/mL did not. BA 9.0mg/mL, the concentration in commercial TA suspensions, was toxic within 5min on each assay for both human and rabbit RPE cells. The major mechanism of cell death was necrosis. In conclusion, BA in commercial TA suspensions injected intravitreally (0.225-9mg/mL) can damage RPE cells. Our in vitro study on benzyl alcohol cytotoxicity has significant clinical implications for intravitreal use of TA. We suggest that, before a commercial TA solution is used intravitreally, the vehicle should be removed to prevent damaging the RPE layer, particularly during macular hole surgery. Commercial development of a preservative-free TA suspension for intraocular use is urged.

  6. Effects of Intravitreal Dexamethasone Implants on Retinal Oxygen Saturation, Vessel Diameter, and Retrobulbar Blood Flow Velocity in ME Secondary to RVO.

    PubMed

    Eibenberger, Katharina; Schmetterer, Leopold; Rezar-Dreindl, Sandra; Wozniak, Piotr; Told, Reinhard; Mylonas, Georgios; Krall, Christoph; Schmidt-Erfurth, Ursula; Sacu, Stefan

    2017-10-01

    To investigate the effects of intravitreal 0.7 mg dexamethasone implants (Ozurdex) on arterial and venous oxygen saturation, retinal vessel diameter, and retrobulbar blood flow velocity in patients with macular edema (ME) due to retinal vein occlusion (RVO). This prospective, nonrandomized clinical trial included 40 eyes of 40 patients with ME due to RVO. Measurements of arterial and venous oxygen saturation and retinal vessel diameters were performed using the Dynamic Vessel Analyzer. The main outcome measure was the retinal arteriovenous oxygen difference, calculated as the difference between arterial and venous oxygenation. Color Doppler imaging was performed for measuring peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) in ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCAs). Follow-up was monthly for 6 months following an initial dexamethasone implant injection. As statistical analysis, a mixed model was performed to investigate the effect treatment. The arteriovenous oxygen difference showed a significant increase (P < 0.01). Arterial oxygenation and vessel diameter did not respond to the treatment (P > 0.05), while the venous oxygen saturation and diameter decreased significantly (P < 0.01) compared to baseline. The retrobulbar blood flow velocities PSV, EDV, and RI showed no change in the OA, CRA, and PCA (P > 0.05). In patients with RVO, intravitreal dexamethasone treatment leads to an increase in arteriovenous oxygen saturation difference indicating improved retinal oxygenation. Arterial oxygenation and vessel diameter showed no response, whereas venous oxygenation and vessel diameter decreased after treatment.

  7. Incidence and Visual Outcomes of Culture-Proven Endophthalmitis Following Dexamethasone Intravitreal Implant.

    PubMed

    Stem, Maxwell S; Todorich, Bozho; Yonekawa, Yoshihiro; Capone, Antonio; Williams, George A; Ruby, Alan J

    2017-04-01

    The rate of endophthalmitis following dexamethasone intravitreal implant (DEX) has varied in large clinical trials. Furthermore, to our knowledge, the optimal management of eyes with endophthalmitis associated with DEX has not been established. To report the incidence of culture-proven endophthalmitis in a single vitreoretinal practice over the course of 3 years and describe the clinical outcomes associated with each case of endophthalmitis. All patients who received DEX between January 14, 2013, and August 31, 2016, were included in this retrospective single-center case series at a private vitreoretinal practice. The patients were identified during a search of the billing records over the period of interest. Cases of endophthalmitis associated with DEX were also identified. Treatment with DEX. Development of endophthalmitis following DEX and the clinical management and outcomes of each case of endophthalmitis. Of the 1051 participants who collectively received 3593 injections of DEX, 4 patients developed endophthalmitis; all 4 patients were white, female, and 60 years or older (mean [SD] age, 75.6 [13] years). Two patients had culture-proven bacterial endophthalmitis after DEX monoinjections (0.06% of injections and 0.2% of patients). Three other cases of endophthalmitis developed after coinjection with bevacizumab (aggregate rate: 0.14% of injections and 0.38% of patients), of which 2 were culture positive. One patient developed endophthalmitis on 2 separate occasions. Vitrectomy was performed in 2 patients, and in 1 of these patients, the implant was removed. All 4 patients were treated with injection of intravitreous vancomycin and ceftazidime. These data suggest that endophthalmitis is a rare event following injection of DEX. However, given the rarity of endophthalmitis following DEX and the heterogeneity among our reported cases, it remains unclear whether the DEX endophthalmitis rate approximates that of intravitreous anti-vascular endothelial growth factor

  8. Intravitreal bevacizumab (Avastin) as treatment for subfoveal choroidal neovascularisation secondary to pathological myopia

    PubMed Central

    Yamamoto, Izumi; Rogers, Adam H; Reichel, Elias; Yates, Paul A; Duker, Jay S

    2007-01-01

    Objective To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin) as treatment for subfoveal choroidal neovascularisation (CNV) due to pathological myopia. Methods Consecutive series of primary or recurrent subfoveal CNV secondary to myopia treated with intravitreal bevacizumab 1.25 mg between August 2005 and January 2006 at the New England Eye Center, Boston, Massachusetts, USA, were reviewed retrospectively. Data from clinical examination, fundus photography, fluorescein angiography, optical coherence tomography and visual acuity were collected. Results There were 11 eyes of 9 patients. 5 of 11 eyes had been treated previously with photodynamic therapy. Pre‐injection visual acuity measured 20/50 to 20/100 in 6 eyes and 20/200 or worse in 5 eyes. After a mean follow‐up of 153 (range 35–224) days, post‐injection visual acuity measured 20/20 to 20/40 in 7 eyes, 20/50 to 20/100 in 1 eye and 20/200 or worse in 3 eyes. Three eyes received two bevacizumab injections and eight eyes received one injection. Visual acuity improved by a mean of +3.5 (range −1 to +8 lines) lines, and 8 of 11 eyes achieved 20/50 or better at the last follow‐up. Central foveal thickness improved from 340 (range 253–664) μm to 234 (range 142–308) μm, representing an average reduction of 103 (range +4 to −356) μm. No injection complications or drug‐related side effects were observed. Conclusions In this small series of eyes with limited follow‐up, intravitreal bevacizumab seems to be safe and potentially efficacious in eyes with subfoveal CNV secondary to pathological myopia. PMID:16870653

  9. Biocompatible reverse thermal gel sustains the release of intravitreal bevacizumab in vivo.

    PubMed

    Rauck, Britta M; Friberg, Thomas R; Medina Mendez, Carlos A; Park, Daewon; Shah, Veeral; Bilonick, Richard A; Wang, Yadong

    2014-01-23

    We assessed the in vivo release profile of bevacizumab from and biocompatibility of poly(ethylene glycol)-poly-(serinol hexamethylene urethane), or ESHU, a thermoresponsive hydrogel administered intravitreally for drug delivery. The technical feasibility of injection was assessed quantitatively via mechanical testing. For in vivo studies, New Zealand White rabbit eyes were injected intravitreally with 0.05 mL of either: ESHU dissolved in 25 mg/mL bevacizumab, ESHU dissolved in PBS, or 25 mg/mL bevacizumab. Clinical examination included IOP measurements and examination with indirect ophthalmoscopy for signs of inflammation. Additionally, eyes were examined histologically following euthanasia. To quantify bevacizumab release, aqueous humor samples were obtained via anterior chamber paracentesis and ELISA was used to determine the concentration of drug weekly. In vitro cytotoxicity testing also was performed using bovine corneal endothelial cells. The ESHU was injected easily through a 31-gauge needle, was well tolerated in vivo, and caused minimal cell death in vitro when compared to other common materials, such as silicone oil. The long-term presence of the gel did not affect IOP, and there was no evidence of inflammation histologically or through indirect observation. The ESHU sustained the release of bevacizumab for over 9 weeks and maintained a drug concentration that averaged 4.7 times higher than eyes receiving bolus bevacizumab injections. To our knowledge, this is the first report demonstrating sustained bevacizumab release in vivo from an intravitreally injected hydrogel formulation, suggesting that this delivery system may be a promising candidate for ocular drug delivery.

  10. Intravitreal administration of erythropoietin and preservation of retinal ganglion cells in an experimental rat model of glaucoma.

    PubMed

    Tsai, James C; Wu, Li; Worgul, Basil; Forbes, Max; Cao, Jingtai

    2005-11-01

    The aim of this pilot study was to evaluate the potential neuroprotective effect of an intravitreal injection of erythropoietin (EPO) on retinal ganglion cell (RGC) preservation in an episcleral vessel cautery-induced rat model of glaucoma. The animals were randomly assigned into an unoperated control group (n = 11) and three experimental groups: episcleral vessel cautery only (EVC: n = 4), episcleral vessel cautery with intravitreal normal saline injection (EVC-NS; n = 5), and episcleral vessel cautery with intravitreal EPO treatment (EVC-EPO; n = 9). The intravitreal injections were limited to 5 mul containing either normal saline alone or 200 ng of EPO in normal saline administered immediately after the cautery procedure. RGCs were labeled retrogradely by FluoroGold neuron tracer 5 to 7 days prior to the collection of eyes at day 21 and counted in whole flat-mounted retinas with fluorescence microscopy. Compared to the RGC counts in retinal specimens from unoperated control rats (12,619 +/- 310), the corresponding RGC counts were significantly decreased in both the EVC (9116 +/- 273; p < 0.005) and EVC-NS (9489 +/- 293; p < 0.005) groups but not significantly decreased in the EVC-EPO (11,212 +/- 414; p = 0.051) treated retinas. A single intravitreal 200 ng dose of EPO appears to have a protective effect on RGC viability in an in vivo rat model of glaucoma. Further experimental studies are needed to confirm these preliminary results and to optimize the appropriate dose and frequency of EPO delivery in animal models of glaucoma.

  11. Mortality in patients treated with intravitreal bevacizumab for age-related macular degeneration.

    PubMed

    Hanhart, Joel; Comaneshter, Doron S; Freier Dror, Yossi; Vinker, Shlomo

    2017-10-10

    The aim of this study is to analyze mortality in patients treated with bevacizumab for wet AMD. We conducted a retrospective case-control study between patients who received intravitreal injections of bevacizumab as the sole treatment for exudative AMD between September 2008 and October 2014 (n = 5385) and age and gender matched controls (n = 10,756). All individuals included in the study were reviewed for sociodemographic data and comorbidities. Survival analysis was performed using adjusted Cox regression, using relevant adjusted variables. During follow-up (maximum: 73 months), 1063 (19.7%) individuals after bevacizumab died compared with 1298 (12.1%) in the control group (P < .001). After adjusted Cox survival regression, mortality differed significantly between the groups, Odds ratio = 1.69, (95% C.I. 1.54-1.84), P < .001. We found an increased long-term mortality in individuals with wet AMD treated with bevacizumab compared to a same age and gender group without wet AMD.

  12. [Foveolar effects of dexamethasone intravitreal implant in central retinal vein occlusion].

    PubMed

    Bikbov, M M; Fayzrakhmanov, R R; Gil'manshin, T R; Gilyazova, I I

    2016-01-01

    To evaluate functional and morphometric parameters of the central retina in patients with postocclusive macular edema treated with dexamethasone intravitreal implant injection. We examined 5 patients (5 eyes) with newly diagnosed central retinal vein occlusion complicated by macular edema, including 4 men and 1 woman aged 55.8±3.65 years (experimental group). All the patients received a single injection of dexamethasone intravitreal implant. The maximum follow-up period was 12 months. The control group consisted of 5 presbiopic patients (10 eyes) aged 59.14±3.14 years. One month after injection, the best corrected visual acuity (BCVA) and central retinal light sensitivity improved (from 0.09±0.03 to 0.19±0.05 and from 3.18±0.19 to 11.07±0.97 dB, correspondingly), while foveolar thickness decreased from 425.36±57.87 to 273.75±36.65 µm. One year after the treatment, BCVA remained high and averaged 0.21±0.14. The total light sensitivity also remained higher than that at baseline, however, decreased down to 4.8±0.76 dB. Optical coherence tomography showed some flatness of the fovea. Foveolar thickness appeared 1.5 times higher than that in the control group and 1.2 times higher than that at the 1-month follow-up after dexamethasone intravitreal implant injection. Over the whole follow-up period, IOP has never significantly exceeded the baseline, optical media remained clear. 1. Dexamethasone intravitreal implant has been shown effective in resolving postocclusive macular edema, improving visual functions, and increasing central retinal light sensitivity within the first month after injection. 2. Positive changes in morphometric parameters of the central retina induced by the injection involve inner segments of photoreceptors as well as the outer nuclear, outer plexiform and inner nuclear layers. The morphofunctional effect persists for no less than 12 months after injection. 3. Over the 1-year follow-up period, there has been no negative influence of the

  13. INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA

    PubMed Central

    Bailey, Clare; Loewenstein, Anat; Massin, Pascale

    2015-01-01

    Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema. Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials. Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose. Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans. PMID:26352555

  14. Automated correlation dimension analysis of optically injected solid state lasers.

    PubMed

    Toomey, J P; Kane, D M; Valling, S; Lindberg, A M

    2009-04-27

    Nonlinear lasers are excellent systems from which to obtain high signal-to-noise experimental data of nonlinear dynamical variables to be used to develop and demonstrate robust nonlinear dynamics analysis techniques. Here we investigate the dynamical complexity of such a system: an optically injected Nd:YVO(4) solid state laser. We show that a map of the correlation dimension as a function of the injection strength and frequency detuning, extracted from the laser output power time-series data, is an excellent mirror of the dynamics map generated from a theoretical model of the system. An automated computational protocol has been designed and implemented to achieve this. The correlation dimension map is also contrasted with prior research that mapped the peak intensity of the output power as an experimentally accessible measurand reflecting the dynamical state of the system [Valling et al., Phys. Rev. A 72, 033810 (2005)].

  15. Intravitreal Ranibizumab for neovascular Age-related macular degeneration in clinical practice: five-year treatment outcomes.

    PubMed

    Zhu, Meidong; Chew, Jamie K; Broadhead, Geoffrey K; Luo, Kehui; Joachim, Nichole; Hong, Thomas; Syed, Adil; Chang, Andrew A

    2015-08-01

    Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are the established standard of care for neovascular age-related macular degeneration (nAMD). However, data on long-term outcomes of this therapy are limited. The purpose of this study was to assess the visual and anatomical outcomes and safety profile of intravitreal ranibizumab in treating nAMD over a period of five years. 208 patients (208 eyes) were included in this retrospective case series study. Intervention was an "as-needed" treatment model. Visual acuity (VA), central macular thickness (CMT), ophthalmic examination, and adverse events (AEs) were assessed in each visit. Snellen VA was converted to Early Treatment Diabetic Retinopathy Study letters for analysis. The average VA improved by 1.9 letters after one year (p = 0.017), and decreased by 2.4 letters over five years of treatment (p = 0.043). At the end of year five, 11.1 % of patients (23/208) had improved VA by more than 15 letters and 68.8 % (143/208) had VA improvement or loss less than or equal to 15 letters, while 20.2 % of patients (42/208) had a loss of more than 15 letters. Patients with VA of less than 35 letters at baseline showed significant VA improvement after five years of treatment. There was a positive relationship between injection numbers and VA improvement over the five-year period, after adjusting for age and baseline VA (p < 0.0005). Mean CMT decreased by 28.3 μm (p < 0.0005) over five years. Ocular AEs, serious adverse events (SAEs), and systemic SAEs occurred in 4.6 %, 0.48 %, and 2 % of patients, respectively, during the follow-up period. The use of intravitreal ranibizumab in an as-needed treatment regimen over a five-year period was effective in maintaining vision in patients with nAMD and in reducing macular thickness, with a relatively low rate of adverse and serious adverse events.

  16. EFFICACY AND FREQUENCY OF INTRAVITREAL AFLIBERCEPT VERSUS BEVACIZUMAB FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.

    PubMed

    Lotfy, Ayman; Solaiman, Kamal A M; Abdelrahman, Ayman; Samir, Ahmed

    2017-08-01

    To compare the safety, efficacy, and frequency of intravitreal injection of aflibercept and bevacizumab for treatment of macular edema secondary to central retinal vein occlusion. Prospective, comparative, randomized, interventional study. Eyes with macular edema secondary to central retinal vein occlusion were randomized between two groups according to the intravitreal injection used. Group A included eyes treated with intravitreal aflibercept, and Group B included eyes treated with intravitreal bevacizumab injections. The inclusion criteria were macular edema secondary to central retinal vein occlusion and follow-up duration of at least 12 months after the first injection. Exclusion criteria were macular ischemia, associated diabetes, hypertensive or renal retinopathy, other retinal disease, and previous anti-vascular endothelial growth factor injection. The main outcome measures are central foveal thickness, best-corrected visual acuity, time intervals between injections, improved retinal nonperfusion, and any reported complication. Group A included 39 patients with a mean age of 57.4 ± 8.2 years. Group B included 40 eyes with a mean age of 56.5 ± 9.1 years. Twelve months after the first injection, central foveal thickness significantly improved from 475.45 ± 71.05 m to 259.11 ± 20.67 m in Group A and from 460.22 ± 89.38 m to 264.29 ± 32.05 m in Group B; best-corrected visual acuity significantly improved from 0.81 ± 0.16 logarithm of the minimum angle of resolution (20/125) to 0.34 ± 0.14 logarithm of the minimum angle of resolution (20/40) in Group A and from 0.73 ± 0.15 logarithm of the minimum angle of resolution (20/100) to 0.33 ± 0.17 logarithm of the minimum angle of resolution (20/40) in Group B; the mean number of injections was 3.72 ± 2.93 in Group A and was 5.44 ± 2.85 in Group B (P < 0.05); and the mean interval between injections was 54.23 ± 8.47 days in Group A and was 35.12 ± 7.76 days in Group B (P < 0.05). Retinal nonperfusion

  17. Posterior Vitreous Detachment With Microplasmin Alters the Retinal Penetration of Intravitreal Bevacizumab (Avastin) in Rabbit Eyes

    PubMed Central

    Goldenberg, David T.; Giblin, Frank J.; Cheng, Mei; Chintala, Shravan K.; Trese, Michael T.; Drenser, Kimberly A.; Ruby, Alan J.

    2010-01-01

    Purpose Intravitreal bevacizumab (Avastin) is frequently used for the treatment of age-related macular degeneration. Previous studies have demonstrated full thickness retinal penetration. Intravitreal recombinant microplasmin (MP) has been shown to successfully induce a posterior vitreous detachment (PVD) and vitreous liquefaction in animals. It has been suggested that a PVD may alter the retinal penetration of molecules in the vitreous cavity. The aim of this study was to compare bevacizumab (BV) retinal penetration in rabbit eyes with and without a MP-induced PVD. Methods Twelve adult rabbits were injected with 0.1 ml (0.4 mg) of MP into the vitreous cavity of one eye. One week later, the rabbits were injected with 0.05 ml (1.25 mg) of BV into both eyes. Both eyes of three rabbits each were harvested at 6, 12, 24, and 72 hours after the BV injection. Frozen retinal cross sections were prepared, and BV retinal penetration was evaluated with immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes from one rabbit were not injected with either agent and used as controls to compare the background autofluorescence. Peripapillary retinal sections were recorded with a digital camera, and intra-retinal BV fluorescence-labeled antibody was measured by qualitative photographic interpretation. Two additional rabbits received an intravitreal injection of 0.1 ml of MP in one eye. One week later, both eyes from each rabbit were enucleated and frozen retinal sections were prepared and analyzed with light microscopy to evaluate for histologic damage. Results Full thickness BV retinal penetration was observed throughout the retina in both eyes of each rabbit. All of the MP-injected eyes exhibited increased antibody labeling in retinas evaluated 6, 12, and 24 hours after BV injection when compared with the contralateral non-MP-injected eyes. By three days after BV injection, all eyes demonstrated decreased antibody labeling compared to earlier time periods

  18. Panretinal photocoagulation versus panretinal photocoagulation plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy

    PubMed Central

    Zhou, Ai-Yi; Zhou, Chen-Jing; Yao, Jing; Quan, Yan-Long; Ren, Bai-Chao; Wang, Jian-Ming

    2016-01-01

    AIM To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria. METHODS The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated. RESULTS Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P<0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular

  19. Combined intravitreal bevacizumab and photodynamic therapy for neovascular age-related macular degeneration.

    PubMed

    Ladewig, Markus S; Karl, Stefanie E; Hamelmann, Victoria; Helb, Hans-Martin; Scholl, Hendrik P N; Holz, Frank G; Eter, Nicole

    2008-01-01

    Our aim was to evaluate the short-term safety and efficacy of combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab in neovascular age-related macular degeneration (AMD). A prospective non-randomized interventional case series of 30 eyes of 30 patients with choroidal neovascularization (CNV) caused by AMD was studied. All patients were treated with PDT followed by an intravitreal injection of bevacizumab (1.5 mg) on the same day. Ophthalmic evaluations included determination of best-corrected visual acuity by using ETDRS charts. CNV lesion characteristics were determined by fluorescein angiography, and retinal morphology by optical coherence tomography. Review examinations were performed 1, 4, and 12 weeks following treatment. The median ETDRS letter scores increased by 3 letters after 4 weeks and 4.3 letters after 12 weeks. Median central retinal thickness decreased from the baseline by 145 microm (week 1), 205 microm (week 4), and 171 microm (week 12), respectively (P < 0.0001, for all comparisons). One patient experienced a transient moderate vision loss after 4 weeks post treatment. Leakage on fluorescein angiography was resolved in all patients at week 12. No significant ocular or systemic side-effects were observed. Short-term results suggest that a single PDT in combination with intravitreal bevacizumab is safe and associated with stabilization of visual acuity and decrease of intraretinal and subretinal fluid accumulation in the macula. Further evaluation of this treatment strategy for neovascular AMD appears warranted.

  20. Cardiovascular involvement in patients with diabetic macular oedema treated with intravitreal ranibizumab in routine clinical practice.

    PubMed

    Díaz-Rodríguez, R; Abreu-González, R; Dolz-Marco, R; Gallego-Pinazo, R

    2017-07-01

    To determine the cardiovascular events in naïve patients with diabetic macular oedema, before and after being treated with intravitreal ranibizumab. A retrospective and descriptive study was conducted on patients with diabetic macular oedema and foveal involvement, who started treatment with intravitreal ranibizumab in 2014 in the Hospital Universitario Nuestra Señora de Candelaria and the Hospital Universitario y Politécnico La Fe. During the follow-up until August 2015, a record was made of parameters, including the prevalence and incidence of stroke and myocardial infarction. Among the 1,324 intravitreal ranibizumab injections administered in 2014, only 159 of them corresponded to treatment initiation in 99 patients, with more than half requiring treatment of both eyes. The study patients included 58.4% males, in the 6th decade of life (Mean=65.93±11.24 years), non-smokers (86.7%), type 2 diabetes (91.9%), hypertension (70.7%), and with dyslipidaemia (65.7%). Prior to treatment initiation, it was found that 6 patients (6.1%) suffered from an acute myocardial infarction, and 8 (8.1%) from stroke, and only one (1%) with post-stroke (P=.039). In our experience it seems that the intravitreal ranibizumab in diabetic macular oedema could be a safe alternative in patients with a history of stroke and myocardial infarction. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Predictive Factors in OCT Analysis for Visual Outcome in Exudative AMD.

    PubMed

    Gamulescu, Maria-Andreea; Panagakis, Georgios; Theek, Carmen; Helbig, Horst

    2012-01-01

    Background. Reliable predictive factors for therapy outcome may enable treating physicians to counsel their patients more efficiently concerning probability of improvement or time point of discontinuation of a certain therapy. Methods. This is a retrospective analysis of 87 patients with exudative age-related macular degeneration who received three monthly intravitreal ranibizumab injections. Visual acuity before initiation of intravitreal therapy and 4-6 weeks after last intravitreal injection was compared and related to the preoperative visualisation of continuity of the outer retinal layers as assessed by OCT: external limiting membrane (ELM), inner photoreceptor segments (IPS), junction between inner and outer segments (IS/OS), and outer photoreceptor segments (OPS). Results. Visual acuity increased in 40 of 87 (46.0%) patients, it remained stable in 25 (28.7%), and 22 (25.3%) patients had decreased visual acuity four to six weeks after triple intravitreal ranibizumab injections. No statistically significant predictive value could be demonstrated for grade of continuity of outer retinal layers concerning visual acuity development. Conclusions. In our series of AMD patients, grade of continuity of outer retinal layers was not a significant predictive value for visual acuity development after triple ranibizumab injections.

  2. Flow injection analysis of MWC fly ash leaching characteristics

    SciTech Connect

    Willemin, J.A.; Nesbitt, C.C.; Dewey, G.R.; Sandall, J.F.; Sutter, L.L.

    1995-11-01

    A completely mixed batch reactor leaching method utilizing flow injection analysis (the CMBR-FIA method) was developed to study the lead leaching characteristics of municipal waste combustor fly ash. Flow injection analysis (FIA) coupled with atomic absorption spectrophotometry enabled the determination of lead concentrations at one minute intervals. The pH and oxidation-reduction potential of the solution were continuously monitored to characterize the leaching conditions. Automatic titration was used to alter the solution pH to defined endpoints. The CMBR-FIA method offers the ability to immediately observe alterations to the leaching solution, and grants the freedom to study a number of parameters concurrently. The CMBR-FIA method is a rapid and reliable means to investigate leaching characteristics. This paper describes the method and demonstrates its use to monitor the leaching of lead from municipal solid waste combustor fly ash as a function of pH. Soluble lead concentrations are shown to increase quickly with decreasing pH. A maximum of 50% of the total lead concentration was available in solution at pH 2. This value gradually decreased with time to over 35% of the total. 16 refs., 6 figs.

  3. Post-intravitreal anti-VEGF endophthalmitis in the United Kingdom: incidence, features, risk factors, and outcomes

    PubMed Central

    Lyall, D A M; Tey, A; Foot, B; Roxburgh, S T D; Virdi, M; Robertson, C; MacEwen, C J

    2012-01-01

    Purpose To describe the incidence, features, management, and risk factors of post-intravitreal anti-VEGF endophthalmitis (PIAE) in patients undergoing treatment for exudative age-related macular degeneration in the United Kingdom. Methods Prospective observational case control study. Forty-seven cases of PIAE were identified through the British Ophthalmological Surveillance Unit from January 2009 to March 2010. Data collected at diagnosis and at 6 months follow-up included patient demographics, intravitreal injection details, pre- and post-injection management, visual acuity, clinical features and management of PIAE, causative organisms, and clinical outcomes. Details were compared with 200 control cases from 10 control centres to identify potential risk factors. Results Estimated PIAE was 0.025%. Culture-positive PIAE incidence was 0.015%. Mean age of presentation was 78 years. Mean number of intravitreal injections before PIAE was 5. Mean days to presentation was 5 (range 1–39). Positive microbiology culture was found in 59.6%. The majority of causative organisms were Gram positive (92.8%). Significant risk factors were failure to administer topical antibiotics immediately after the injection (P=0.001), blepharitis (P=0.006), subconjunctival anaesthesia (P=0.021), patient squeezing during the injection (P=0.021), and failure to administer topical antibiotics before anti-VEGF injection (P=0.05). Discussion The incidence of PIAE in the United Kingdom is comparable to other studies at a rate of 0.025%. The most common causative organisms were Gram positive. Measures to minimise the risk of PIAE include treatment of blepharitis before injection, avoidance of subconjunctival anaesthesia, topical antibiotic administration immediately after injection with consideration to administering topical antibiotics before injection. PMID:23060022

  4. Intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to age-related macular degeneration in an Indian population.

    PubMed

    Azad, Raj Vardhan; Khan, Mansur Ali; Chanana, Bhuvan; Azad, Shorya

    2008-01-01

    To investigate the 6-month safety profile and clinical outcomes of intravitreal bevacizumab for treating subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). We performed a prospective nonrandomized interventional study of 40 consecutive patients (40 eyes) with subfoveal CNV due to AMD. Patients underwent standard ophthalmic examination, optical coherence tomography, and fundus fluorescein angiography. All patients were administered one or more intravitreal injections of bevacizumab (1.25 mg) as primary therapy. Outcomes were also analyzed in subgroups based on lesion type (classic or occult) and lesion size (< or =3000 microm or >3000 microm). At the 6 months' follow-up, mean best-corrected visual acuity (BCVA) improved from 20/160 to 20/100 (P = 0.014), and the mean contrast sensitivity improved from 0.38 to 0.62 (P = 0.001). The mean greatest linear diameter and mean central macular thickness significantly decreased from 3.79 mm to 2.4 mm (P = 0.0001) and from 438.5 microm to 363 microm (P = 0.0001), respectively. Visual acuity gain of 15 letters or more was seen in 20% of patients, and the gain was more in the small-lesion subgroup (31.5%) than in the large-lesion subgroup (9.5%). No significant adverse effects were observed. Intravitreal bevacizumab is a safe and effective modality for treatment of CNV secondary to AMD. A significant improvement in BCVA with intravitreal bevacizumab was observed for all lesion types.

  5. Modified electrokinetic sample injection method in chromatography and electrophoresis analysis

    DOEpatents

    Davidson, J. Courtney; Balch, Joseph W.

    2001-01-01

    A sample injection method for horizontal configured multiple chromatography or electrophoresis units, each containing a number of separation/analysis channels, that enables efficient introduction of analyte samples. This method for loading when taken in conjunction with horizontal microchannels allows much reduced sample volumes and a means of sample stacking to greatly reduce the concentration of the sample. This reduction in the amount of sample can lead to great cost savings in sample preparation, particularly in massively parallel applications such as DNA sequencing. The essence of this method is in preparation of the input of the separation channel, the physical sample introduction, and subsequent removal of excess material. By this method, sample volumes of 100 nanoliter to 2 microliters have been used successfully, compared to the typical 5 microliters of sample required by the prior separation/analysis method.

  6. Intravitreal toxicology in rabbits of two preparations of 1-O-octadecyl-sn-glycerol-3-phosphonoformate, a sustained-delivery anti-CMV drug.

    PubMed

    Cheng, L; Hostetler, K Y; Gardner, M F; Avila, C P; Bergeron-Lynn, G; Keefe, K S; Wiley, C A; Freeman, W R

    1999-06-01

    To determine intraocular toxicity and efficacy of the lipid prodrug of foscarnet, 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA), as a long-acting, nontoxic intravitreous injectable drug delivery system for cytomegalovirus (CMV) retinitis. ODG-PFA was synthesized by coupling the phosphonate residue of PFA to the 3 hydroxyl of 1-O-octadecyl-sn-glycerol and formulated as micelles and liposomes at concentrations so that, after injection into the rabbit vitreous, the resultant intravitreal concentrations were 0.2 mM, 0.63 mM, and 2 mM in micellar formulation and 0.02 mM, 0.063 mM, 0.2 mM, and 0.63 mM for liposomal formulation. The compounds were injected, and toxicology evaluations were performed. Intravitreal injections of micellar ODG-PFA resulted in aggregation of the material in vitreous and variable local retinal damage. Intravitreal injections of the liposomal ODG-PFA revealed even dispersion of the compounds and a clear vitreous, using final concentration in the vitreous of 0.2 mM. No intraocular toxicity was found with the 0.632 mM final concentration. The 50% inhibitory concentration (IC50) for CMV of ODG-PFA was 0.43+/-0.27 microM, and the therapeutic index of ODG-PFA after intravitreal injection was estimated to be 1470:1. Lipid-derivatized foscarnet liposome formulations may be a useful long-acting delivery system for the therapy of CMV retinitis.

  7. Intravitreal ziv-aflibercept for macular edema following retinal vein occlusion

    PubMed Central

    Paulose, Remya; Chhablani, Jay; Dedhia, Chintan J; Stewart, Michael W; Mansour, Ahmad M

    2016-01-01

    Aim To report the efficacy of intravitreal ziv-aflibercept injections in eyes with macular edema due to retinal vein occlusions (RVOs). Methods Consecutive patients with persistent or recurrent macular edema (central macula thickness >250 μm) due to RVO were enrolled in this prospective study. Study eyes received intravitreal injections of ziv-aflibercept (1.25 mg/0.05 mL) at baseline. Patients were reassessed monthly for 4 months and given additional injections pro re nata for worsening best-corrected visual acuity (BCVA), intraretinal edema or subretinal fluid seen on spectral domain optical coherence tomography, or central macular thickness (CMT) measurements >250 μm. The primary endpoint was improvement in mean CMT at 4 months. Secondary endpoints included improvement in mean BCVA, and ocular and systemic safety signals. Results Nine eyes (five central and four branch RVOs) of nine patients were enrolled. The mean ± standard deviation CMT decreased from 604±199 μm at baseline to 319±115 μm (P=0.001) at 1 month and to 351±205 μm (P=0.026) at 4 months. The mean BCVA did not improve significantly from baseline (1.00 LogMAR) to the 1-month (0.74 LogMAR; P=0.2) and 4-month (0.71 LogMAR; P=0.13) visits. No safety signals were noted. Conclusion In this small prospective study, intravitreal ziv-aflibercept significantly improved mean CMT in eyes with persistent or recurrent macular edema due to RVOs. Prospective, randomized trials comparing ziv-aflibercept with standard pharmacotherapy are needed to better define efficacy and safety. PMID:27703326

  8. [Intravitreal triamcinolone combined with grid laser photocoagulation for patients with cystoid macular edema and advanced diabetic retinopathy: pilot study].

    PubMed

    Arévalo, J F; Fernández, C F; Mendoza, A J; García, R A; Arévalo, F A

    2013-10-01

    To determine if primary intravitreal injection of triamcinolone acetonide (TA) plus grid laser photocoagulation (GLP) is effective in treating cystoid diabetic macular edema (DME). Prospective comparative non-randomized clinical trial. Fourteen eyes (14 patients) diagnosed with cystoid DME were treated with GLP according to the Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines, plus an intravitreal injection of 4 mg of TA. A matched control group (16 eyes [16 patients]) treated with GLP was selected retrospectively from our medical records. Best-corrected visual acuity (BCVA), and quantitative change in optical coherence tomography (OCT) macular thickness were assessed. Mean follow up was 14.9 months (12 to 19 months). In 3 (21.4%) eyes BCVA increased > 2 ETDRS lines, in 5 (35.7%) eyes BCVA remained the same, and BCVA decreased >2 ETDRS lines in 6 (42.8%) eyes. Central macular thickness, as measured by OCT, decreased a mean of 106.2 μm (30.2%). The difference with the control group was not statistically significant (P = .2). Four (28.5%) eyes developed an increased in intraocular pressure in our study group. Although all of our patients showed an improvement of cystoid DME by means of OCT and fluorescein angiography, 42.8% (6 eyes) lost 2 or more lines in BCVA with primary intravitreal injection of TA plus GLP. Primary intravitreal injection of TA plus GLP may not be effective for cystoid DME at 12-months. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  9. Simple and clean determination of tetracyclines by flow injection analysis

    NASA Astrophysics Data System (ADS)

    Rodríguez, Michael Pérez; Pezza, Helena Redigolo; Pezza, Leonardo

    2016-01-01

    An environmentally reliable analytical methodology was developed for direct quantification of tetracycline (TC) and oxytetracycline (OTC) using continuous flow injection analysis with spectrophotometric detection. The method is based on the diazo coupling reaction between the tetracyclines and diazotized sulfanilic acid in a basic medium, resulting in the formation of an intense orange azo compound that presents maximum absorption at 434 nm. Experimental design was used to optimize the analytical conditions. The proposed technique was validated over the concentration range of 1 to 40 μg mL- 1, and was successfully applied to samples of commercial veterinary pharmaceuticals. The detection (LOD) and quantification (LOQ) limits were 0.40 and 1.35 μg mL- 1, respectively. The samples were also analyzed by an HPLC method, and the results showed agreement with the proposed technique. The new flow injection method can be immediately used for quality control purposes in the pharmaceutical industry, facilitating monitoring in real time during the production processes of tetracycline formulations for veterinary use.

  10. Functional and structural effect of intravitreal indocyanine green, triamcinolone acetonide, trypan blue, and brilliant blue g on rat retina.

    PubMed

    Creuzot-Garcher, Catherine; Acar, Niyazi; Passemard, Marie; Bidot, Samuel; Bron, Alain; Bretillon, Lionel

    2010-09-01

    The purpose of this study was to evaluate the functional and structural damage of the retina after intravitreal injections of four different dyes in the rat. Rats were injected intravitreally with indocyanine green (ICG), trypan blue, triamcinolone acetonide, or brilliant blue G in the right eye. The other eye was injected with saline and served as a control. Simultaneous bilateral electroretinograms were recorded before injection and 7 and 28 days after injection. Histology and immunohistochemistry analyses with antibodies recognizing glial fibrillary acidic protein and protein kinase C were performed 28 days after the initial injection on both eyes. Seven days after dye injection, the electroretinogram response of the treated eyes was altered in each group. At 1 month, eyes injected with triamcinolone acetonide, trypan blue, or brilliant blue G fully recovered, whereas eyes treated with ICG had A-wave and B-wave reduction of 65% and 63%, respectively. The inner nuclear layer thickness was statistically decreased in the ICG group (P = 0.003) but not with other dyes. Protein kinase C staining was decreased in the ICG group only, but no abnormal qualitative staining was found with either glial fibrillary acidic protein or protein kinase C antibodies with any dye. Among the four tested dyes, only ICG led to functional and structural retinal damage.

  11. Two or more dexamethasone intravitreal implants in treatment-naïve patients with macular edema due to retinal vein occlusion: subgroup analysis of a retrospective chart review study.

    PubMed

    Dugel, Pravin U; Capone, Antonio; Singer, Michael A; Dreyer, Richard F; Dodwell, David G; Roth, Daniel B; Shi, Rui; Walt, John G; Scott, Lanita C; Hollander, David A

    2015-09-04

    Dexamethasone intravitreal implant (DEX implant) is a biodegradable, sustained-release implant that releases dexamethasone for up to 6 months. We evaluated the efficacy and safety of DEX implant in the treatment of macular edema secondary to retinal vein occlusion (RVO) in treatment-naïve patients. A multicenter, retrospective, open-label chart review study investigated the efficacy and safety of DEX implant treatment in 289 patients with macular edema secondary to branch or central RVO (BRVO, CRVO) who received ≥2 treatments with DEX implant in the study eye. Concomitant adjunctive RVO treatments were permitted. Data collected from the time of the first implant (baseline) to 3-6 months after the last implant included best-corrected visual acuity (BCVA) and central retinal thickness measured with optical coherence tomography. In this subgroup analysis, we evaluated outcomes in patients who had received no previous treatment for RVO complications. Thirty-nine patients were treatment-naïve at the time of their first DEX implant (18 BRVO, 21 CRVO). Before the initial DEX implant, the mean duration of macular edema in treatment-naïve patients was 4.9 months, mean central retinal thickness was 550 μm, and mean Early Treatment Diabetic Retinopathy Study BCVA was 8.5 lines (20/125 Snellen). Treatment-naïve patients received a mean of 2.9 implants, either as monotherapy (n = 12) or with adjunctive RVO treatments (n = 27). The mean interval between implants was 177 days. After the first through sixth implants, mean changes from baseline BCVA ranged from +3.0 - +8.0 lines, and mean decreases from baseline central retinal thickness ranged from 241-459 μm. BCVA improved in both BRVO and CRVO and in both phakic and pseudophakic eyes. Overall, 83.8 % of treatment-naïve patients gained ≥2 lines in BCVA, 70.3 % gained ≥3 lines in BCVA, and 56.4 % achieved central retinal thickness ≤250 μm. The most common adverse event was increased intraocular

  12. Cost-effectiveness of intravitreal aflibercept versus other treatments for wet age-related macular degeneration in Japan.

    PubMed

    Yanagi, Yasuo; Fukuda, Aya; Barzey, Victor; Adachi, Kenji

    2017-02-01

    This analysis estimated the cost-effectiveness of intravitreal aflibercept injection(s) (IAI) for wet age-related macular degeneration (wAMD) compared with other treatments in Japan. This was a cost-utility analysis based on published data. A state-transition cohort model was constructed with six health states based on best-corrected visual acuity in the better-seeing eye. The cycle time was 4 weeks, and the time horizon was 12 years. The model compared IAI 2 mg every 8 weeks (2q8) for 2 years after three initial monthly injections, ranibizumab as needed, ranibizumab 0.5 mg every 4 weeks (0.5q4), pegaptanib sodium 0.3 mg every 6 weeks, verteporfin photodynamic therapy (PDT), and best supportive care, assumed to include medical management and monitoring, but no active therapy. Costs (expressed as Japanese yen [JPY]) and quality-adjusted life years (QALYs) gained were estimated for each treatment and discounted at 2.0%. Input data were obtained from clinical studies, the Japanese drug tariff and social insurance reimbursement schedule, and expert opinion. The analysis was conducted from the societal perspective, including medical costs as well as costs of blindness. IAI 2q8 was dominant (i.e. more effective in terms of QALYs and less costly) to all other comparators (ranibizumab as needed, ranibizumab 0.5q4, pegaptanib sodium, PDT, and best supportive care), as shown by the incremental cost-utility ratio (i.e. cost per QALY gained). The strengths of the analysis include the wide range of comparators evaluated and the use of Japanese-specific utility data. The limitations include the use of one eye, inclusion of published data up to 2 years only, and assumptions on disease course over 5 years. IAI 2q8 was more effective in terms of QALYs and less costly compared with other treatments for wAMD in Japan.

  13. [A technique of rhesus monkey neural progenitor cells intravitreal transplant to rats].

    PubMed

    Bian, Hui; Fan, Yao-Dong; Guo, Li-Yun; Yu, Hua-Lin

    2012-02-01

    To investigate a simple and effective intraocular xenotransplant technique of rhesus monkey neural progenitor cells to rats, mechanical injury was induced in the rat's right retina. And the GFP-labeled rhesus monkey neural progenitor cells suspension was slowly injected into the vitreous space of the right injured and left control eye. Confocal image suggested that the xenografted cells survived in both the injured and control eye, meanwhile the cells integrated in the injured right retina. The results demonstrated that intravitreal xenotransplant could be adopted as a simple and reliable method.

  14. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

    PubMed Central

    Sánchez-Castro, Grimelda Yuriana; Hitos-Fájer, Alejandra; Mendoza-Schuster, Erick; Velez-Montoya, Raul; Velasco-Barona, Cecilio Francisco

    2008-01-01

    We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema. PMID:19668770

  15. Neuroprotective effects of BDNF and GDNF in intravitreally transplanted mesenchymal stem cells after optic nerve crush in mice

    PubMed Central

    Hu, Zong-Li; Li, Ni; Wei, Xin; Tang, Li; Wang, Ting-Hua; Chen, Xiao-Ming

    2017-01-01

    AIM To assess the neuro-protective effect of bone marrow mesenchymal stem cells (BMSCs) on retinal ganglion cells (RGCs) following optic nerve crush in mice. METHODS C56BL/6J mice were treated with intravitreal injection of PBS, BMSCs, BDNF-interference BMSCs (BIM), and GDNF-interference BMSCs (GIM) following optic nerve crush, respectively. The number of surviving RGCs was determined by whole-mount retinas and frozen sections, while certain mRNA or protein was detected by q-PCR or ELISA, respectively. RESULTS The density (cell number/mm2) of RGCs was 410.77±56.70 in the retina 21d after optic nerve crush without any treatment, compared to 1351.39±195.97 in the normal control (P<0.05). RGCs in BMSCs treated eyes was 625.07±89.64/mm2, significantly higher than that of no or PBS treatment (P<0.05). While RGCs was even less in the retina with intravitreal injection of BIM (354.07+39.77) and GIM (326.67+33.37) than that without treatment (P<0.05). BMSCs injection improved the internal BDNF expression in retinas. CONCLUSION Optic nerve crush caused rust loss of RGCs and intravitreally transplanted BMSCs at some extent protected RGCs from death. The effect of BMSCs and level of BDNF in retinas are both related to BDNF and GDNF expression in BMSCs. PMID:28149774

  16. Jupiter Icy Moons Orbiter interplanetary injection period analysis

    NASA Technical Reports Server (NTRS)

    Kowalkowski, Theresa D.; Kangas, Julie A.; Parcher, Daniel W.

    2006-01-01

    This paper investigates the sensitivity of the planned Jupiter Icy Moons Orbiter mission to variations in interplanetary injection date, magnitude, and direction, starting in a low-Earth assembly orbit. These results are used to determine the frequency and number of injection opportunities from a processing assembly obit. It is shown that the use of a low-thrust propulsion system with a nuclear-electric power source would allow the interplanetary trajectory performance to be relatively insensitive to variations in injection conditions. This result yields many injection opportunities due to the long injection period and consecutive orbits with favorable geometry.

  17. The remote effects of intravitreal anti-VEGF therapy

    PubMed Central

    Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V

    2016-01-01

    Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the “Prof. Dr. Theodor Burghele” Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life PMID:27928444

  18. The remote effects of intravitreal anti-VEGF therapy.

    PubMed

    Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V

    2016-01-01

    Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.

  19. The role of intravitreal chemotherapy for retinoblastoma

    PubMed Central

    Manjandavida, Fairooz P; Shields, Carol L

    2015-01-01

    Targeted therapy in retinoblastoma (RB) is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC), retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC. PMID:25827545

  20. Equivalent circuit analysis of the RHIC injection kicker

    SciTech Connect

    Hahn, H.; Ratti, A.

    1997-07-01

    The RHIC injection kicker is built as a traveling wave structure in order to assure the required 95 nsec risetime in the deflection strength. The kicker is constructed from 14 cells, each 7.5 cm long, with alternating ferrite and high-permittivity dielectric sections. The cell structure permits an analysis of the electrical properties of the kicker using lumped L, C, and R circuit elements. Their values are obtained directly from impedance measurements of the full-length kicker, the inductance and shunt capacitance values by measuring the input impedance at 1 MHz with the output shorted and open, respectively. A lossy series resonance circuit in each cell is found to reproduce the measured input impedance of the terminated kicker up to {approximately}100 MHz. The validity of the equivalent circuit was confirmed by comparing the measured output current pulse shape time with that computed by the P-Spice program.

  1. Evaluation of vitreoretinal interface changes in patients receiving intravitreal anti-VEGF therapy.

    PubMed

    Kinra, Vartika; Singh, Satvir; Khanduja, Sumeet; Nada, Manisha

    2017-03-15

    To study the effects of repeated intravitreal injection of anti-VEGF drug bevacizumab on the vitreoretinal interface (VRI). Patients undergoing intravitreal injection of bevacizumab were enrolled. Eyes with media haze, uveitis, high myopia, history of cataract surgery or laser capsulotomy in last 6 months and complicated pseudophakia were excluded. VRI evaluation was done monthly for a minimum of 6 months. The nature and timing of the change(s) event was recorded. A total of 100 eyes were evaluated. Thirty-seven eyes developed new vitreoretinal interface change event (VICE). Pseudophakia (OR = 5.23, 95% CI = 1.99-14.07, p = 0.001), pre-injection VRI abnormality (OR = 2.63, 95% CI = 1.13-6.14, p = 0.024) and older age at enrollment (62.6 ± 13.9 vs. 56.3 ± 14 years) were risk factors for development of VICE. Eighty percent of interface events occurred in the first 3 months of therapy. Eight needed surgical intervention for consequences of vitreoretinal separation. VICE is not infrequent in eyes receiving anti-VEGF therapy though rarely need surgical intervention. The first 3 months are the critical months to watch out for these events. The treating ophthalmologists must keep the risk factors for development of in mind and monitor and counsel patients accordingly.

  2. High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration.

    PubMed

    Lee, Dong Kyu; Kim, Soon Hyun; You, Yong Sung; Kwon, Oh Woong

    2016-08-01

    Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Increasing the dose of bevacizumab in refractory PED may be a possible treatment option.

  3. Combination Systemic and Intravitreal Antiviral Therapy in The Management of Acute Retinal Necrosis Syndrome (An American Ophthalmological Society Thesis)

    PubMed Central

    Flaxel, Christina J.; Yeh, Steven; Lauer, Andreas K.

    2013-01-01

    Purpose: To compare the outcomes of combination systemic and intravitreal antiviral therapy vs systemic antiviral therapy alone for treating acute retinal necrosis syndrome (ARN). We hypothesize that combination therapy might result in superior visual acuity (VA) and retinal detachment (RD) outcomes vs traditional systemic antiviral therapy alone. Methods: A retrospective, interventional, comparative single-center study of patients with ARN. We reviewed demographic data, herpesvirus diagnoses, polymerase chain reaction (PCR) results, VA, RD, and the use of systemic and intravitreal antiviral therapy. Outcome measures included VA improvement by 2 or more lines, severe visual loss, VA ≤20/200, and RD. Results: We studied 29 eyes of 24 patients, treated from 1987 through 2009. Mean age was 42.6 years and mean follow-up was 44.0 months. Twelve patients (14 eyes) were treated with combined systemic and intravitreal antiviral therapy and 12 patients (15 eyes) with systemic therapy alone. Kaplan-Meier survival analysis revealed that patients receiving combination intravitreal and systemic antiviral therapy were more likely to have VA improved by 2 lines or greater (P=.006). Patients receiving combination therapy also showed a decreased incidence of progression to severe visual loss (0.13/patient-years [PY]) compared to patients receiving systemic therapy alone (0.54/PY, P=.02) and had decreased incidence of RD (0.29/PY vs 0.74/PY, P=.03). Conclusions: Combination oral and intravitreal antiviral therapy may improve visual and functional outcomes in patients with ARN. Clinicians should consider prompt administration of combination systemic and intravitreal antiviral therapy as first-line treatment for patients with clinical features of ARN. PMID:24385671

  4. Intravitreal bevacizumab treatment for refractory diabetic macular edema.

    PubMed

    Yuksel, Erdem; Ozdek, Sengul; Yuksel, Nılay; Hasanreisoglu, Berati

    2013-12-01

    To evaluate the effect of intravitreal bevacizumab (IVB) on visual function and retinal thickness in patients with refractory diabetic macular edema (DME). Eyes with DME treated with IVB which were resistant to different previous treatments were enrolled in this retrospective, non-randomized series study. Each patient underwent a complete ophthalmic examination including best-corrected visual acuity (BCVA), slit-lamp examination, intraocular pressure measurement, fundus examination, retinal thickness measurement with optic coherence tomography at baseline and at each visit. Digital fundus fluorescein angiography was performed at baseline for each patient. A total of 71 eyes of 59 patients (36 male and 23 female) were included in the study. All eyes had focal laser photocoagulation (71 eyes, 100 %) and had one other additional treatment including an intravitreal (23 eyes, 32 %) or subtenon (18 eyes, 25 %) injection of triamcinolone acetonide. The mean follow-up period was 9.79 ± 8.6 months and the mean number of IVB treatments was 2.01 ± 1.06 (min-max, 1-4). Mean logMAR BCVA was 0.88 ± 0.4 at baseline, 0.78 ± 0.4 at 4 weeks and 0.79 ± 0.4 at the last visit (p = 0.036). The mean central foveal thickness was 515.4 ± 150.3 μm at baseline which significantly decreased to 367.01 ± 166.6 μm at 4 weeks (p = 0.0001) and 338.1 ± 159.7 μm at the last visit (p = 0.0001). Sixteen percent of the eyes did not respond to IVB treatment. IVB treatment for refractory DME seems to be effective and safe and repeated treatments are necessary for a significant portion of the cases.

  5. Flow-injection enzymatic analysis for glycerol and triacylglycerol.

    PubMed

    Wu, Li-Chen; Cheng, Chien-Ming

    2005-11-15

    A flow-injection enzymatic analytical system was developed for determination of glycerol and triacylglycerol based on enzymatic reactions in capillary followed by electrochemical detection. The hydrogen peroxide produced from the enzyme reaction was monitored by a platinum-based electrochemical probe. Different immobilization strategies on silica support were studied. The best and most effective configuration found for the measurement of glycerol and triacylglycerols in this system was the tandem connection of a lipase column and a silica-fused capillary column coimmobilized with glycerokinase (GK) and glycerol-3-phosphate oxidase (GPO). Lipase helps the breakdown of triacylglycerol to yield free fatty acids and glycerol, while glycerokinase catalyzes the adenosine-5-triphosphate-dependent phosphorylation of glycerol to yield alpha-glycerol phosphate, which can subsequently be oxidized by 3-glycerol phosphate oxidase to produce hydrogen peroxide. Response-surface methodology (RSM) was applied to optimize the proposed system for glycerol. Experiment settings were designed by central composite design to investigate the combined effects of pH, flow rate, reaction temperature, and ATP concentration on collected signals. The fitted model, per RSM, showed that the optimum conditions of the system are 2 mM ATP in 0.1 M carbonate buffer (pH 11.0), flow rate of 0.18 mL/min, temperature of 35 degrees C, 20 microL of sample injection, and applied voltage of 0.650 V. The proposed biosensing system using lipase, GK, and GPO exhibited a flow-injection analysis peak response of 2.5 min and a detection limit of 5 x 10(-5) M glycerol (S/N = 3) with acceptable reproducibility (CV < 4.30%). It also had linear working ranges from 10(-4) to 10(-2) M for glycerol and from 10(-3) to 10(-2) M for triacylglycerol. The capillary enzyme reactor was stable up to 2 months in continuous operation, and it was possible to analyze up to 15 samples per hour. The present biosensing system holds

  6. Determination of a No-Observable Effect Level for Endotoxin Following a Single Intravitreal Administration to Dutch Belted Rabbits.

    PubMed

    Bantseev, Vladimir; Miller, Paul E; Bentley, Ellison; Schuetz, Chris; Streit, Tim M; Christian, Brian J; Farman, Cindy; Booler, Helen; Thackaberry, Evan A

    2017-03-01

    The purpose of this study was to characterize the inflammatory response and determine a no-observable effect level (NOEL) in rabbit eyes after endotoxin intravitreal (ITV) injection. Fifty-three naïve male Dutch Belted rabbits were treated with a single 50-μL ITV injection ranging from 0.01 to 0.75 endotoxin units/eye (EU/eye) and monitored for up to 42 days post treatment. Ophthalmic examination included slit-lamp biomicroscopy and indirect ophthalmoscopy. Laser flare photometry was performed in a subset of animals. On days 2, 8, 16, and 43, a subset of animals was necropsied and eyes processed for histopathological evaluation. Intravitreal injection of endotoxin at ≥0.05 EU/eye resulted in a dose-related anterior segment inflammation response. No aqueous flare or cell response was noted in the 0.01 EU/eye dose group. A more delayed posterior segment response characterized by vitreal cell response was observed beginning on day 5, peaking on day 9, and decreasing starting on day 16 that persisted at trace to a level of 1+ on day 43. Microscopy findings of infiltrates of minimal mixed inflammatory cells in the vitreous and subconjunctiva and proteinaceous fluid in the anterior chamber and/or vitreous were observed in eyes given ≥0.1 EU/eye. We defined the NOEL for ITV endotoxin to be 0.01 EU/eye, suggesting that the vitreal cavity is more sensitive to the effects of endotoxin than the anterior segment and aqueous chamber. These data highlight the importance of assessing endotoxin level in intravitreal formulations, as levels as low as 0.05 EU/eye may confound the safety evaluations of intravitreal therapeutics in rabbits.

  7. Screening of conditions controlling spectrophotometric sequential injection analysis

    PubMed Central

    2011-01-01

    Background Despite its potential benefits over univariate, chemometrics is rarely utilized for optimizing sequential injection analysis (SIA) methods. Specifically, in previous vis-spectrophotometric SIA methods, chemometrically optimized conditions were confined within flow rate and reagent concentrations while other conditions were ignored. Results The current manuscript reports, for the first time, a comprehensive screening of conditions controlling vis-spectrophotometric SIA. A new diclofenac assay method was adopted. The method was based on oxidizing diclofenac by permanganate (a major reagent) with sulfuric acid (a minor reagent). The reaction produced a spectrophotometrically detectable diclofenac form. The 26 full-factorial design was utilized to study the effect of volumes of reagents and sample, in addition to flow rate and concentrations of reagents. The main effects and all interaction order effects on method performance, i.e. namely sensitivity, rapidity and reagent consumption, were determined. The method was validated and applied to pharmaceutical formulations (tablets, injection and gel). Conclusions Despite 64 experiments those conducted in the current study were cumbersome, the results obtained would reduce effort and time when developing similar SIA methods in the future. It is recommended to critically optimize effective and interacting conditions using other such optimization tools as fractional-factorial design, response surface and simplex, rather than full-factorial design that used at an initial optimization stage. In vis-spectrophotometric SIA methods those involve developing reactions with two reagents (major and minor), conditions affecting method performance are in the following order: sample volume > flow rate ≈ major reagent concentration >> major reagent volume ≈ minor reagent concentration >> minor reagent volume. PMID:21333024

  8. Simultaneous Therapy with Intravitreal Dexamethasone Implant and Bevacizumab for the Treatment of Macular Edema

    PubMed Central

    de ANDRADE, Felipe L.; LOPES, Flavio S.; de ANDRADE, Gabriel C.; PRATA, Tiago S.; MAIA, André

    2016-01-01

    To investigate the safety profile and benefits of a short-term simultaneous treatment regimen combining two drugs—an intravitreal implant of dexamethasone with an intravitreal injection of bevacizumab—in patients with macular edema. This was a retrospective, non-randomized, open-label case series study. Patients were treated between April 2014 and July 2015 and were diagnosed with recurrent macular edema secondary to diabetic retinopathy and retinal vein occlusion. They underwent simultaneous treatment with an intravitreal injection of bevacizumab (1.25 mg) and an intravitreal implant of dexamethasone (0.7 mg). Patients were evaluated at baseline and at each subsequent visit with a complete ophthalmological examination and spectral-domain optical coherence tomography (OCT) scans. They were examined 24 hours after the treatment, and then followed up after 30 days and 60 days. Twenty patients (representing 20 eyes) were included in the study. At the time of injection (i.e., baseline), the best-corrected visual acuity (BCVA) was 0.758 ± 0.42 logarithm of the minimum angle of resolution (logMAR). It improved significantly to 0.51 ± 0.33 logMAR at 1 month and to 0.5 ± 0.34 logMAR at 2 months (P ≤ 0.03). The median baseline central macular thickness (CMT) was 542 µm (interquartile range, 466 – 751 µm). The median CMT decreased significantly to 321 µm (interquartile range, 288–381 µm) at 1 month and 310 µm (interquartile range, 286 – 354 µm) at 2 months (P ≤ 0.0002). The mean intraocular pressure (IOP) increased from 14.9 ± 2.29 mmHg (at baseline) to 16.5 ± 2.99 mmHg (P = 0.04) after 2 months. Two (10%) eyes showed cataract progression. There were no other ocular or systemic complications for the duration of this study. Simultaneous therapy combining a dexamethasone implant plus bevacizumab for macular edema may be an attractive treatment regimen with an acceptable safety profile. PMID:28289686

  9. Evaluation of Intravitreal Ranibizumab on the Surgical Outcome for Diabetic Retinopathy With Tractional Retinal Detachment

    PubMed Central

    Dong, Feng; Yu, Chenying; Ding, Haiyuan; Shen, Liping; Lou, Dinghua

    2016-01-01

    Abstract This study aims to investigate intravitreal injection of Ranibizumab on the surgical outcome for diabetic patients who had tractional retinal detachment but did not receive any preoperative retinal photocoagulation. Ninety-seven patients (97 eyes) who had diabetic retinopathy with tractional retinal detachment were enrolled to receive 23-G pars plana vitrectomy (PPV). They were assigned to an experimental group (Group I, n = 47 eyes) and a control group (Group II, n = 50 eyes). The patients in Group I were given 1 injection of intravitreal Ranibizumab (Lucentis 0.5 mg/0.05 mL) 1 week before surgery, whereas those in Group II went down to surgery directly. Follow-ups were performed for 6 months to 3 years (16 ± 6 months), and indicators observed included postoperative best-corrected visual acuity, complications, and retinal thickness in the macula measured by optical coherence tomography. In Group I, BCVA improved from logMAR 1.92 ± 0.49 to logMAR 0.81 ± 0.39 following surgery, whereas in Group II, BCVA improved from logMAR 1.91 ± 0.49 to logMAR 0.85 ± 0.41. There was significant postoperative gain in vision, but there was no significant difference between the 2 groups at postoperative follow-up visits. The mean duration of vitrectomy in Group I and Group II was (40 ± 7) minutes and (53 ± 9) minutes, respectively, with significant difference. Iatrogenic breaks were noted in 5 eyes (11%) in the experimental group and 17 eyes (34%) in the control group; the difference was significant. The retinal thickness in the macula measured by OCT was (256 ± 44) μm and (299 ± 84) μm in Group I and Group II respectively with significant difference. Besides, there were significantly more eyes in Group II that required silicone oil tamponade and postoperative retinal photocoagulation. 23-G PPV combined with intravitreal tamponade and panretinal photocoagulation still remains an effective regimen for the

  10. Effect of intravitreal bevacizumab on diabetic macular edema with hard exudates

    PubMed Central

    Jeon, Sohee; Lee, Won Ki

    2014-01-01

    Background We evaluated the efficacy of intravitreal bevacizumab on diabetic macular edema with subfoveal and perifoveal hard exudates. Materials and methods Eleven eyes (11 patients) exhibiting diabetic macular edema with subfoveal and perifoveal hard exudates were included in this prospective, nonrandomized interventional pilot study. All patients were treated with monthly scheduled intravitreal bevacizumab injections for 6 months. Changes in the Early Treatment Diabetic Retinopathy Study best corrected visual acuity, amount of hard exudates on fundus photography, and macular edema detected by central subfield thickness on spectral domain optical coherence tomography after six serial injections, were assessed. The amount of hard exudates at each visit was evaluated as pixels in fundus photography, using an Adobe Photoshop program. Results Ten of 11 patients completed follow-up. The mean Early Treatment Diabetic Retinopathy Study best corrected visual acuity was 59.9±5.7 letters (Snellen equivalent, 20/63) at baseline evaluation. The best corrected visual acuity exhibited no significant difference at month 6 compared with at baseline (57.9±6.0 letters or 20/70 at month 6; P=0.085). At month 6, mean central subfield thickness decreased from 370.4±56.5 to 334.6±65.0 μm (P=0.009). The mean amount of hard exudates increased from 4467.1±2736.1 to 6592.4±2498.3 pixels at month 6 (P=0.022). No serious adverse events occurred. Conclusion Continuous intravitreal bevacizumab was found to have no benefit in visual acuity and amount of hard exudates, despite the improvement of macular edema at 6 months. PMID:25143708

  11. Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity: A Phase 1 Dosing Study.

    PubMed

    Wallace, David K; Kraker, Raymond T; Freedman, Sharon F; Crouch, Eric R; Hutchinson, Amy K; Bhatt, Amit R; Rogers, David L; Yang, Michael B; Haider, Kathryn M; VanderVeen, Deborah K; Siatkowski, R Michael; Dean, Trevano W; Beck, Roy W; Repka, Michael X; Smith, Lois E; Good, William V; Hartnett, Mary Elizabeth; Kong, Lingkun; Holmes, Jonathan M

    2017-06-01

    Intravitreous bevacizumab (0.25 to 0.625 mg) is increasingly used to treat type 1 retinopathy of prematurity (ROP), but there remain concerns about systemic toxicity. A much lower dose may be effective while reducing systemic risk. To find a dose of intravitreous bevacizumab that was lower than previously used for severe ROP, was effective in this study, and could be tested in future larger studies. Between May 2015 and September 2016, 61 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, phase 1 dose de-escalation study. One eye of 10 to 14 infants received 0.25 mg of intravitreous bevacizumab. If successful, the dose was reduced for the next group of infants (to 0.125 mg, then 0.063 mg, and finally 0.031 mg). Diluted bevacizumab was delivered using 300 µL syringes with 5/16-inch, 30-gauge fixed needles. Bevacizumab injections at 0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg. Success was defined as improvement in preinjection plus disease or zone I stage 3 ROP by 5 days after injection or sooner, and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Fifty-eight of 61 enrolled infants had 4-week outcomes completed; mean birth weight was 709 g and mean gestational age was 24.9 weeks. Success was achieved in 11 of 11 eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9 eyes at 0.031 mg. A dose of bevacizumab as low as 0.031 mg was effective in 9 of 9 eyes in this phase 1 study and warrants further investigation. Identifying a lower effective dose of bevacizumab may reduce the risk for neurodevelopmental disability or detrimental effects on other organs.

  12. Intravitreal bevacizumab as primary treatment for retinal angiomatous proliferation: twelve-month results.

    PubMed

    Gharbiya, Magda; Allievi, Francesca; Recupero, Vincenzo; Martini, Delia; Mazzeo, Luigi; Gabrieli, Corrado Balacco

    2009-06-01

    To evaluate the short-term efficacy and safety of intravitreal bevacizumab for the treatment of retinal angiomatous proliferation. Seventeen eyes from 16 patients with newly diagnosed retinal angiomatous proliferation underwent intravitreal injections of bevacizumab, 1.25 mg. The patients were scheduled for three monthly bevacizumab injections. Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, central macular thickness on optical coherence tomography, and fluorescein angiographic findings were examined before and after treatment. Patients were followed-up for 12 months. The mean best-corrected visual acuity (+/- standard deviation [SD]) at baseline was 39.53 (+/-10.40) letters (Snellen equivalent: 20/42). At 12 months after treatment the mean best-corrected visual acuity (+/-SD) improved significantly (P = 0.0000001) to 47.88 (+/-11.78) letters (Snellen equivalent: 20/28). Best-corrected visual acuity improved 3 ETDRS lines or more in 3 (17.65%) of 17 treated eyes, 14 (82.35%) eyes were stable, and 15 (88.23%) eyes gained 1 or more ETDRS lines. The mean central macular thickness (+/-SD) at baseline was 297 (+/-60.72) microm. At 12 months after treatment, the mean central macular thickness (+/-SD) reduced significantly (P = 0.00001) to 237 (+/-28.80) microm. At the 12-month follow-up, absence of fluorescein leakage was demonstrated in 14 (82%) of 17 treated eyes. No ocular or systemic adverse effects from treatment were encountered. The 12-month results of intravitreal bevacizumab for retinal angiomatous proliferation are very promising with no apparent short-term safety concerns. Treated eyes had a significant functional and anatomical improvement. Further studies will be needed to better determine long-term efficacy and safety.

  13. Intravitreal aflibercept in neovascular age-related macular degeneration previously treated with ranibizumab

    PubMed Central

    Lim, Rachel Hui Fen; Gupta, Bhaskar; Simcock, Peter

    2017-01-01

    AIM To report the change in visual acuity and central macular thickness (CMT) following treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration (nAMD) with suboptimum response to ranibizumab. METHODS This was a retrospective study. The inclusion criteria were patients with nAMD who responded poorly to ranibizumab. Patients then received either 3 consecutive aflibercept injections followed by pro re nata (PRN) treatment or PRN alone. Primary endpoints were mean change in best-corrected visual acuity (BCVA) and CMT at 12mo. Secondary endpoints were number of injections and adverse events. RESULTS Forty-nine eyes from 49 patients met the inclusion criteria and completed 12-month follow up on aflibercept. Thirty-eight eyes received 3 consecutive aflibercept injections followed by PRN treatment and 11 eyes received PRN injections alone. At 12mo, mean BCVA improved by one letters (logMAR 0.56±0.31 to 0.54±0.34) and mean CMT decreased from 303.9±82.1 to 259.2±108.3 µm. Four percent of eyes gained 15 letters or more, 6% lost more than 15 letters and the remaining 90% had stable BCVA. The mean number of aflibercept injections was 6. There was one case of infectious endophthalmitis. CONCLUSION Intravitreal aflibercept in patients with nAMD with a previous suboptimal response to ranibizumab resulted in an anatomical improvement in macular appearance at 12mo without a corresponding improvement in visual acuity. PMID:28393034

  14. Chronic cystoid macular oedema treated with intravitreal dobesilate

    PubMed Central

    Cuevas, Pedro; Outeiriño, Luis A; Angulo, Javier; Giménez-Gallego, Guillermo

    2012-01-01

    Dobesilate is an anti-inflammatory and antipermeability agent. Intravitreal administration of this compound is a therapeutically beneficial agent in the treatment of chronic cystoid macular oedema. PMID:22778475

  15. Contralateral eye-to-eye comparison of intravitreal ranibizumab and a sustained-release dexamethasone intravitreal implant in recalcitrant diabetic macular edema

    PubMed Central

    Thomas, Benjamin J; Yonekawa, Yoshihiro; Wolfe, Jeremy D; Hassan, Tarek S

    2016-01-01

    Objective To compare the effects of intravitreal ranibizumab (RZB) or dexamethasone (DEX) intravitreal implant in cases of recalcitrant diabetic macular edema (DME). Methods Retrospective, interventional study examining patients with symmetric bilateral, center-involved DME recalcitrant to treatment with RZB, who received DEX in one eye while the contralateral eye continued to receive RZB every 4–5 weeks for a study period of 3 months. Results Eleven patients (22 eyes) were included: mean logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) for the DEX arm improved from 0.415 (standard deviation [SD] ±0.16) to 0.261 (SD ±0.18) at final evaluation, and mean central macular thickness (CMT) improved from 461 µm (SD ±156) to 356 µm (SD ±110; net decrease: 105 µm, P=0.01). Mean logMAR VA for the RZB arm improved from 0.394 (SD ±0.31) to 0.269 (SD ±0.19) at final evaluation. Mean CMT improved from 421 µm (SD ±147) to 373 µm (SD ±129; net decrease: 48 µm, P=0.26). Conclusion A subset of recalcitrant DME patients demonstrated significant CMT reduction and VA improvement after a single DEX injection. PMID:27621587

  16. Computed tomography analysis of third webspace injections for interdigital neuroma.

    PubMed

    Hembree, W Chad; Groth, Adam T; Schon, Lew C; Guyton, Gregory P

    2013-04-01

    Injection for interdigital neuroma (IDN) may not selectively target the common digital nerve. We investigated the anatomical localization and extent of extravasation with injection for IDN. Two fellowship-trained foot and ankle surgeons injected radiopaque contrast into the third webspace of 49 cadaveric specimens (29 with 2 mL and 20 with 1 mL). Computed tomography scan of each specimen was obtained. An independent blinded foot and ankle surgeon analyzed the scans. All injections were accurate. Contrast was found in the second (greater than 70%) and fourth (greater than 30%) webspaces in both injection volume groups. No contrast was found within the third metatarsophalangeal joint. Extravasation extent was significantly greater with 2 mL versus 1 mL of solution in the medial to lateral (27.9 [7.8] mm vs 23.7 [6.0] mm; P = .05) and distal to proximal (52.1 [13.7] mm vs 40.4 [16.1] mm; P = .01) planes. No differences were observed in extravasation extent between surgeons. Injection for IDN was accurate, and extravasation extended into adjacent webspaces in a large percentage of specimens with both solution volumes. Lower extent of extravasation with 1 mL of solution did not indicate better selectivity of injection. Steroid injections for interdigital neuroma were accurate for therapeutic purposes but not diagnostic, except potentially for distinguishing webspace pain from joint pain.

  17. Toxicity assessment of intravitreal triamcinolone and bevacizumab in a retinal explant mouse model using two-photon microscopy.

    PubMed

    Schlichtenbrede, Frank C; Mittmann, Wolfgang; Rensch, Florian; Vom Hagen, Franziska; Jonas, Jost B; Euler, Thomas

    2009-12-01

    Intravitreal drug administration leads to high intraocular concentrations with potentially toxic effects on ocular tissues. This study was an assessment of the toxicity of triamcinolone and bevacizumab in living retinal explants using two-photon (2P) microscopy. Wild-type mice received intravitreal injections of triamcinolone, bevacizumab, or vehicle. Ten and 45 days after injection, wholemounted retinal explants were incubated with the fluorescent dye sulforhodamine 101 (SR101) to analyze morphology and tissue damage with 2P microscopy ex vivo. Retinas that received the same treatment were stained for apoptosis (TUNEL) and glial activation (GFAP). An intravitreal injection of NMDA (N-methyl-d-aspartate) was used as a positive control to ensure the fidelity of detection of retinal damage with ex vivo 2P microscopy. Overall retinal morphology was undisturbed after all procedures and time points. NMDA injection resulted in a strong increase in the number of SR101-labeled cells and increased apoptosis and glial activation when compared with sham-injected eyes. This result was in contrast to exposure to bevacizumab, which caused no appreciable damage. After triamcinolone treatment, marked damage in the inner retina was observed. However, damaged cells were restricted to sharply demarcated areas, and only mild changes in TUNEL-positive cells and GFAP activation was observed when compared to sham-injected eyes. 2P microscopy in combination with SR101 staining allows fast morphologic assessment of living retinal explants and can be used to evaluate adverse effects on retinal viability of test substances. Bevacizumab treatment did not cause any detectable retinal damage, whereas triamcinolone was associated with substantial, although spatially restricted, damage.

  18. Two-year results of combined intravitreal anti-VEGF agents and photodynamic therapy for retinal angiomatous proliferation.

    PubMed

    Saito, Masaaki; Iida, Tomohiro; Kano, Mariko

    2013-03-01

    To clarify the efficacy of a combination of intravitreal anti-vascular endothelial growth factor (VEGF) injections and photodynamic therapy (PDT), over 24 months, for patients with symptomatic retinal angiomatous proliferation (RAP). We retrospectively reviewed 13 treatment-naïve eyes of 12 patients (7 men, 5 women; age range (mean), 63-92 (77) years) treated with intravitreal bevacizumab (IVB) plus PDT as initial treatment. Retreatment was performed with IVB plus PDT until February 2009 or intravitreal ranibizumab and PDT from March 2009. Mean best-corrected visual acuity (BCVA) significantly improved from 0.26 at baseline to 0.40 at 24 months (P = 0.013). The mean improvement in BCVA at 24 months from baseline was 1.79 lines. The central retinal thickness decreased significantly from 431 to 142 microns at 24 months (P < 0.0001). Complete occlusion of the retinal-retinal anastomosis was achieved in seven of the 10 eyes at 24 months. The mean number of PDT treatments during 24 months was 2.8 and the mean number of injections was 3.4. Geographic atrophy was seen in four eyes without significant decline of VA at 24 months. Combined anti-VEGF and PDT for RAP patients effectively maintained or improved VA and reduced exudation, without severe adverse events, over 24 months.

  19. Cost comparison of intravitreal aflibercept with bevacizumab and ranibizumab for the treatment of wet age-related macular degeneration.

    PubMed

    Shaikh, Adeel H; Toussaint, Brian W; Miller, Daniel M; Petersen, Michael R; Foster, Robert E; Riemann, Christopher D; Hutchins, Robert K; Sisk, Robert A

    2015-01-01

    To test the hypothesis that although intravitreal aflibercept (IVA) is expected to be more expensive, the extra cost of treatment would not result in additional vision gain compared with intravitreal bevacizumab (IVB) for the treatment of wet age-related macular degeneration (AMD). A retrospective chart review of patients receiving IVB or intravitreal ranibizumab (IVR) who were subsequently changed to IVA for active wet AMD. Thirty-three eyes were included in the study. The mean number of IVB, IVR, and IVA injections per eye over a 6-month period was seven, six, and five, respectively. Visual outcomes were similar in all three groups at the end of the study period. The average drug cost of IVB, IVR, and IVA injections per eye over 6 months was $326, $11,400, and $9,720, respectively. Aflibercept may allow a modest extension of the treatment interval, but cost makes IVA an expensive alternative without a visual benefit compared with IVB in patients with active wet AMD. Copyright 2015, SLACK Incorporated.

  20. Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization.

    PubMed

    Traversi, Claudio; Nuti, Elisabetta; Marigliani, Davide; Cevenini, Gabriele; Balestrazzi, Angelo; Martone, Gianluca; Caporossi, Tomaso; Tosi, Gian Marco

    2015-04-01

    To evaluate the long-term efficacy of bevacizumab in the treatment of choroidal neovascularization (CNV) secondary to pathological myopia. In this retrospective single-center non-comparative study the medical records of 29 eyes from 29 patients with naïve CNV secondary to high myopia and at least 42 months of follow up were reviewed. All eyes received a loading dose of one intravitreal injection per month for two consecutive months and were retreated on an as-needed basis during the course of follow up. The main outcome measures were post-treatment ETDRS best-corrected visual acuity (BCVA) and visual stabilization over time. Stepwise linear regression analysis was performed to identify prognostic factors for visual acuity gain and final visual acuity outcome at 42 months. At 42 months of follow-up bevacizumab was associated with the maintenance of significant benefits in visual acuity compared to baseline. No adverse ocular or systemic effects from treatment were encountered. No statistically significant correlations were found between BCVA change and any of the quantitative variables. However, when final BCVA was taken as a dependent variable and CNV size and pre-treatment VA were included as predictors, a bivariate model was identified by stepwise regression which gave a 75 % of explained variance. Bevacizumab treatment was found to be efficacious in the treatment of myopic CNV, resulting in stable gains in visual acuity lasting at least 42 months, without any adverse ocular or general events. Myopic CNV size was identified as a significant prognostic factor.

  1. Neuroprotective effect of systemic and/or intravitreal rosuvastatin administration in rat glaucoma model

    PubMed Central

    Unlu, Metin; Aktas, Zeynep; Gocun, Pinar Uyar; Ilhan, Sevil Ozger; Hasanreisoglu, Murat; Hasanreisoglu, Berati

    2016-01-01

    AIM To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS Ocular hypertension was induced in right eyes of Long-Evans rats (n=30) by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups: oral rosuvastatin, intravitreal rosuvastatin, oral+intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell (RGC) number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) staining and the expression of glial fibrillary acidic protein (GFAP) in RGC layer was also examined. RESULTS A significant intraocular pressure (IOP) elevation was seen (P=0.002). Elevated IOP resulted in a significant decrease in number of RGCs in group 5 (70.33±8.2 cells/mm2) when compared with controls (92.50±13.72 cells/mm2; P=0.03). The RGC number in group 1 (92.4±7.3 cells/mm2) was significantly higher than group 5 (P=0.03). The numbers of RGC in groups 2, 3 (57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2) were comparable with that of group 5 (P=0.18 and P=0.31). The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreactivity. CONCLUSION Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. However intravitreal rosuvastatin showed a contrary effect and further studies are required. PMID:27158600

  2. Development of devices for self-injection: using tribological analysis to optimize injection force.

    PubMed

    Lange, Jakob; Urbanek, Leos; Burren, Stefan

    2016-01-01

    This article describes the use of analytical models and physical measurements to characterize and optimize the tribological behavior of pen injectors for self-administration of biopharmaceuticals. One of the main performance attributes of this kind of device is its efficiency in transmitting the external force applied by the user on to the cartridge inside the pen in order to effectuate an injection. This injection force characteristic is heavily influenced by the frictional properties of the polymeric materials employed in the mechanism. Standard friction tests are available for characterizing candidate materials, but they use geometries and conditions far removed from the actual situation inside a pen injector and thus do not always generate relevant data. A new test procedure, allowing the direct measurement of the coefficient of friction between two key parts of a pen injector mechanism using real parts under simulated use conditions, is presented. In addition to the absolute level of friction, the test method provides information on expected evolution of friction over lifetime as well as on expected consistency between individual devices. Paired with an analytical model of the pen mechanism, the frictional data allow the expected overall injection system force efficiency to be estimated. The test method and analytical model are applied to a range of polymer combinations with different kinds of lubrication. It is found that material combinations used without lubrication generally have unsatisfactory performance, that the use of silicone-based internal lubricating additives improves performance, and that the best results can be achieved with external silicone-based lubricants. Polytetrafluoroethylene-based internal lubrication and external lubrication are also evaluated but found to provide only limited benefits unless used in combination with silicone.

  3. Development of devices for self-injection: using tribological analysis to optimize injection force

    PubMed Central

    Lange, Jakob; Urbanek, Leos; Burren, Stefan

    2016-01-01

    This article describes the use of analytical models and physical measurements to characterize and optimize the tribological behavior of pen injectors for self-administration of biopharmaceuticals. One of the main performance attributes of this kind of device is its efficiency in transmitting the external force applied by the user on to the cartridge inside the pen in order to effectuate an injection. This injection force characteristic is heavily influenced by the frictional properties of the polymeric materials employed in the mechanism. Standard friction tests are available for characterizing candidate materials, but they use geometries and conditions far removed from the actual situation inside a pen injector and thus do not always generate relevant data. A new test procedure, allowing the direct measurement of the coef