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Sample records for intravitreal injection analysis

  1. Intravitreal injection

    MedlinePlus

    Retinal vein occlusion-intravitreal injection; Triamcinolone-intravitreal injection; Dexamethasone-intravitreal injection; Lucentis-intravitreal injection; Avastin-intravitreal injection; Bevacizumab-intravitreal injection; Ranibizumab- ...

  2. 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. PMID:27257676

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

    PubMed Central

    Yuksel-Elgin, Cansu; Elgin, Ceyhun

    2016-01-01

    AIM To report on intraocular pressure (IOP) after intravitreal injections of triamcinolone acetonide. METHODS Systematic literature review of studies that investigated the effects of an injection of triamcinolone intravitreal triamcinolone acetonide on IOP was conducted according to the Cochrane Collaboration methodology and the reported effects have been analyzed with Meta-analysis. RESULTS We found that the IOP follows an inverted-U shape pattern over time starting with an average value of 14.81±1.22 mm Hg before the injection, rising to a maximum of 19.48±2.15 mm Hg after one month of injection and falling down to 16.16±1.92 mm Hg after 6mo. Moreover, country of study, age, previous history of glaucoma and gender compositions matter for cross-study were different in reported IOP changes. CONCLUSION Our findings may be helpful in determining pressure elevation risk of intravitreal triamcinolone acetonide therapy as well as comparing it with those of more recent therapies such as the anti-vascular endothelial growth factor agents. PMID:26949624

  5. 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

  6. Intraocular pressure changes related to intravitreal injections of ranibizumab: analysis of pseudophakia and glaucoma subgroup.

    PubMed

    Demirel, Sibel; Yanik, Ozge; Batioglu, Figen; Ozmert, Emin

    2015-08-01

    The purpose of this study was to determine intraocular pressure (IOP) changes following intravitreal ranibizumab injections and to investigate the effect of pre-existing glaucoma and pseudophakia. Two hundred and two eyes of 175 patients who received repeated intravitreal ranibizumab injections were included in this study. IOP measurements were obtained at both 30 min and 24 h after each injection. IOP changes after the first, third, sixth, ninth, and twelfth injections were analyzed. Data gotten from subgroups with pre-existing glaucoma and pseudophakia were also analyzed. The mean number of injections was 4.81 ± 2.7 (range: 3-18), while the mean IOP prior to the first intravitreal ranibizumab injection was 15.11 ± 2.8 (9-25) mmHg. At the last visit, IOP was 14.66 ± 2.8 (9-22) mmHg. There was no cumulative increase in IOP at either 30 min or 24 h values throughout repeated injections. Pseudophakic patients had significantly lower mean IOP values at 30 min after all injections except for twelfth. The number of eyes with an IOP higher than 21 mm Hg and the mean IOP values were significantly higher in patients with pre-existing glaucoma at 30 min after the first and third injections. Pseudophakic eyes are less prone to immediate IOP spikes than phakic eyes. Pre-existing glaucoma may be a potential risk factor for uncontrolled IOP spikes immediately after intravitreal injection; nonetheless, this effect is usually transient and does not cause long-term problems. Also, ranibizumab injections can be administered safely under close monitoring. PMID:25079762

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

    PubMed Central

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

    2015-01-01

    Aims 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. Methods 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. Results 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). Conclusion 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. PMID:26451092

  8. Rate of intraoperative complications during cataract surgery following intravitreal injections.

    PubMed

    Hahn, P; Jiramongkolchai, K; Stinnett, S; Daluvoy, M; Kim, T

    2016-08-01

    PurposeTo investigate the effect of prior intravitreal injections on intraoperative and postoperative complication rates associated with cataract surgery.MethodsA retrospective cohort analysis reviewed 10 105 cataract surgery procedures performed by experienced surgeons at the Duke Eye Center from 1 January 2005 to 10 December 2012. A group of 197 eyes with prior intravitreal injections was compared with an equal number of matched control eyes without prior injection using the Fisher's exact test of difference in proportions and the Wilcoxon rank-sum test of difference in means. Outcomes analyzed included baseline demographic information, preoperative clinical characteristics, prevalence of intraoperative complications, and postoperative intraocular pressure, glaucoma surgery, and glaucoma medication requirement through 1 year following cataract surgery.ResultsAn increased rate of intraoperative complications was identified during cataract surgery in eyes with prior intravitreal injections compared with control eyes (3 vs 0%, P=0.030). Injection eyes required more glaucoma medications at 1 year, but no difference was identified if steroid injections were excluded. No difference in postoperative IOP or glaucoma surgery was identified. No cases of endophthalmitis were reported.ConclusionsA history of intravitreal injections may be a risk factor for cataract surgery-related intraoperative complications. We hypothesize this may be due to unidentified iatrogenic lens trauma during intravitreal injections. Particular attention to the posterior capsule during preoperative assessment and intraoperatively is recommended in eyes undergoing cataract surgery with a prior history of intravitreal injections. PMID:27229705

  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.]. PMID:27548453

  10. Global reported endophthalmitis risk following intravitreal injections of anti-VEGF: a literature review and analysis

    PubMed Central

    Sigford, Douglas K; Reddy, Shivani; Mollineaux, Christine; Schaal, Shlomit

    2015-01-01

    Purpose To report on endophthalmitis occurrence and associated risk factors following the intravitreal injection of anti-VEGF agents based on a review of published literature. Materials and methods A Medline search was performed using the terms “bevacizumab” and “ranibizumab”. A total of 534 English-language articles of varying design and published from 2006 to November 2013 were analyzed for endophthalmitis occurrence and contributing perioperative factors. Results A total of 445,503 injections were counted. There were 103 cases of postinjection endophthalmitis in 176,124 injections (0.058%) with bevacizumab (Avastin) versus 79 cases in 269,379 injections (0.029%) with ranibizumab (Lucentis). This difference was due to a significantly higher occurrence of culture-negative endophthalmitis associated with bevacizumab injections. Culture-positive risk was not statistically different between the two drugs. The reported use of postinjection topical antibiotics increased the risk of culture-positive endophthalmitis. No association was found with the use of povidone iodine, a lid speculum, a mask, or an operating room. Streptococcus spp. were the most prevalent causative organism, accounting for nine of 54 (17%) of all culture-positive cases. Conclusion Reported postinjection endophthalmitis occurred significantly more in patients treated with bevacizumab than those treated with ranibizumab. However, culture-positive occurrence was similar. Despite the potential for contamination at the time of drug compounding, bevacizumab does not appear to confer a higher risk of culture-positive endophthalmitis than ranibizumab. This study also suggests antibiotic use may increase endophthalmitis occurrence. PMID:25999685

  11. Intravitreal Injection--Technique and Safety.

    PubMed

    Lai, Timothy Y Y; Liu, Shu; Das, Sudipta; Lam, Dennis S C

    2015-01-01

    Intravitreal (IVT) injection of therapeutic agents has become one of the most commonly performed procedures in ophthalmology. Over the past decade, a number of guidelines have been published that recommend proper techniques to increase the safety of IVT injections. Among the various complications of IVT injections, endophthalmitis can be sight threatening. The reported endophthalmitis rates after IVT injection range from 0.020% to 0.085%, which are higher than what would be expected from a simple, fast, and relatively atraumatic procedure. The 2 key issues involved in the prevention of endophthalmitis are pre-IVT injection disinfection using povidone-iodine (PVI) and the use of topical antibiotics as prophylaxis. Whereas 5% PVI for 5 minutes is most commonly used in cataract surgery for disinfection, the duration in IVT injection is much less and can be as short as 30 seconds. Further studies seem warranted to investigate whether longer duration of PVI application in IVT injection can lower the endophthalmitis rate. Recent data suggest that there is inadequate evidence to support the routine use of prophylactic pre-, peri-, or postinjection antibiotics to reduce the risk of endophthalmitis. However, as many confounding factors such as the PVI regimens were not standardized in previous studies, it is too soon to make a concrete conclusion. Despite the availability of published guidelines, considerable variations still exist in real-life clinical situations. In this article, we describe our IVT injection practice protocol and compare it with the most recent international guidelines. Finally, a summary table that shows the clinical features of true, sterile, and pseudoendophthalmitis is presented. PMID:26649760

  12. Safety of bilateral intravitreal injections delivered in a teaching institution.

    PubMed

    Chao, Daniel L; Gregori, Ninel Z; Khandji, Joyce; Goldhardt, Raquel

    2014-07-01

    Intravitreal injection is one of the most common in-office procedures performed in ophthalmic practices. In teaching institutions such as the Veterans Affairs (VA) Hospitals, patient care is delivered by physicians-in-training, while mastering intravitreal injection technique. Infectious endophthalmitis and visual loss are the most feared complications of intravitreal injections, especially in the context of recent outbreaks caused by contaminated compounded medications. Ophthalmologists and ophthalmic educators increasingly face the dilemma of timing as well as balancing the risks and benefits of bilateral treatments required by many patients. In this editorial, we discuss published reports of bilateral injections, summarize our experience with bilateral intravitreal injections in a teaching setting at the Miami VA Hospital and list our recommendations for minimizing the risk of infectious endophthalmitis. PMID:24815986

  13. Intravitreal Bevacizumab in Retinopathy of Prematurity: Inject or Not?

    PubMed

    Hapsari, Dini; Sitorus, Rita S

    2014-01-01

    This article is aimed to review and summarize the indications, outcomes and safety profiles regarding the use of intravitreal bevacizumab in patients with retinopathy of prematurity (ROP) as reported in previous studies with no intention to compare the efficacy between intravitreal bevacizumab and laser photocoagulation.Literature search was conducted in databases such as PubMed, Cochrane, Ovid, and Ophthalmology Advance using the terms "ROP," "antiangiogenic," "antivascular endothelial growth factor," "intravitreal bevacizumab," and "Avastin."Eight prospective studies of 278 eyes of ROP infants and 15 retrospective studies involving 385 eyes of ROP infants treated with intravitreal bevacizumab were found. Bevacizumab was used as monotherapy, adjunctive therapy, and/or combined therapy.The varied use of intravitreal bevacizumab in treating ROP and he limited number of landmark studies contribute to the difficulties in drawing a strong conclusion in this review. Intravitreal bevacizumab was more commonly injected in: (1) type 1 ROP zone I and/or posterior zone II; (2) aggressive posterior ROP with poor retinal visualization in which laser photocoagulation would be difficult to perform; and (3) stage 4 ROP before vitrectomy. All cases demonstrated regression of neovascular activity during a varied follow-up period (from 1 week to 1 month) after injection. However, recurrence may occur. Follow-up until 80 weeks of postmenstrual age is thus recommended. Acceleration of fibrous traction is the most common ocular adverse effect after injection, whereas the systemic adverse effect remains uncertain. Landmark studies of the efficacy of intravitreal bevacizumab injection in treating ROP are warranted. PMID:26107980

  14. Survey of intravitreal injection techniques among retina specialists in Israel

    PubMed Central

    Segal, Ori; Segal-Trivitz, Yael; Nemet, Arie Y; Geffen, Noa; Nesher, Ronit; Mimouni, Michael

    2016-01-01

    Purpose The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines. Methods All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques. Results Overall, 66% (52/79) completed the survey. Most (98%) do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71%) use sterile surgical draping. All respondents apply topical analgesics and a majority (69%) measure the distance from the limbus to the injection site. A minority (21%) displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%). Less than half routinely assess postinjection optic nerve perfusion (44%). A majority (92%) apply prophylactic antibiotics immediately after the injection. Conclusion The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques that combine safety and efficacy while causing as little discomfort to the patients as possible. PMID:27366050

  15. An outbreak of Ralstonia pickettii endophthalmitis following intravitreal methotrexate injection

    PubMed Central

    Choudhury, Himadri; Jindal, Animesh; Pathengay, Avinash; Flynn, Harry W

    2015-01-01

    Purpose To report an outbreak of endophthalmitis in three eyes of two patients following intravitreal methotrexate, caused by Ralstonia pickettii. Design Retrospective, noncomparative, consecutive case series. Methods Medical records and microbiology results of two patients who presented with acute endophthalmitis following intravitreal methotrexate injection in November 2013 were reviewed. Results Following intravitreal injections, the patients experienced pain and decrease in vision in the affected eye within 24 hours of receiving intravitreal methotrexate injection. The presenting visual acuity in case 1 was 20/50 in the left eye. The presenting visual acuity in case 2 was hand motions in the right eye and counting fingers at 1 m in the left eye. Both the patients received methotrexate prepared in the same manufacturing facility. Both the patients underwent vitreous biopsy and intravitreal injection of vancomycin 1 mg/0.1 mL, amikacin 400 µg/0.1 mL, and dexamethasone 400 µg/0.1 mL. Microbiology cultures from vitreous, and used and unused vials of methotrexate from the same batch grew R. pickettii. After 8 months of follow-up, both the patients had visual acuity 20/60 or better. Conclusion R. pickettii can be rarely associated with outbreak of endophthalmitis. Timely intervention can be associated with good visual outcome in such patients. PMID:26150690

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

    PubMed

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

    2016-01-01

    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. PMID:27440854

  17. Cytomegalovirus Retinitis after Intravitreal Bevacizumab Injection in an Immunocompetent Patient

    PubMed Central

    Bae, So Hyun; Kim, Tae Wan; Chung, Hum

    2013-01-01

    We report a case of cytomegalovirus (CMV) retinitis after intravitreal bevacizumab injection. A 61-year-old woman with diabetic macular edema developed dense vitritis and necrotizing retinitis 3 weeks after intravitreal bevacizumab injection. A diagnostic vitrectomy was performed. The undiluted vitreous sample acquired by vitrectomy was analyzed by polymerase chain reaction and culture. Polymerase chain reaction of the vitreous was positive for CMV DNA. Other laboratory results did not show evidence of other infectious retinitis and systemic immune dysfunction. Human immunodeficiency virus antibodies were also negative. After systemic administration of ganciclovir, retinitis has resolved and there has been no recurrence of retinitis during the follow-up period of 12 months. Ophthalmologists should be aware of potential risk for CMV retinitis after intravitreal bevacizumab injection. PMID:23372384

  18. 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. PMID:23666517

  19. Isolated sixth nerve palsy after intravitreal ranibizumab injection.

    PubMed

    Caglar, Cagatay; Kocamis, Sücattin Ilker; Durmus, Mustafa

    2016-09-01

    After intravitreal ranibizumab injection for diabetic macular edema (DME) in a 55-year-old man, the patient was admitted to our ophthalmology clinic with the complaint of diplopia. Given the results of the patient's history, physical exam, and negative magnetic resonance imaging (MRI), we believed that the patient had a sixth nerve palsy related to ranibizumab injection. To the best of our knowledge, this is the first case with isolated abducens palsy after ranibizumab injection. PMID:26340018

  20. Prevention of intraocular pressure rise following intravitreal injection.

    PubMed Central

    Morlet, N; Young, S H

    1993-01-01

    The intraocular pressure change produced by an intravitreal injection of ganciclovir, 2 mg in 0.1 ml, was studied in patients with cytomegalovirus retinitis. Using a Tono-pen XL to measure the intraocular pressure (IOP) of four patients (six eyes) we found the mean pressure immediately following injection was 44.5 mm Hg. Measurements taken on separate occasions after a 30 mm Hg decompression of the eye for 15 minutes before the injection showed a mean IOP of only 20.6 mm Hg after the injection. Mercury bag decompression of the eye significantly reduced the rise in IOP following intravitreal injection (difference in the mean IOP rise = 26.4 mm Hg, df = 54, t = 7.67, p < 0.001). Without ocular decompression before injection, all patients complained of temporary loss of vision, and reflux of the injection solution was frequently observed. Use of ocular decompression also reduced the discomfort of the injection. Throughout the full course of treatment by this means there were no adverse effects on the visual acuity. This technique is recommended to those performing intravitreal injections. Images PMID:8218055

  1. Intravitreal Injection of AAV2 Transduces Macaque Inner Retina

    PubMed Central

    Yin, Lu; Greenberg, Kenneth; Hunter, Jennifer J.; Dalkara, Deniz; Kolstad, Kathleen D.; Masella, Benjamin D.; Wolfe, Robert; Visel, Meike; Stone, Daniel; Libby, Richard T.; DiLoreto, David; Schaffer, David; Flannery, John; Williams, David R.

    2011-01-01

    Purpose. Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized morphology of the high-acuity human fovea. This was a study of inner retina transduction in the macaque, a primate with ocular characteristics most similar to that of humans. Methods. In vivo imaging and histology were used to examine GFP expression in the macaque inner retina after intravitreal injection of AAV vectors containing five distinct promoters. Results. AAV2 produced pronounced GFP expression in inner retinal cells of the fovea, no expression in the central retina beyond the fovea, and variable expression in the peripheral retina. AAV2 vector incorporating the neuronal promoter human connexin 36 (hCx36) transduced ganglion cells within a dense annulus around the fovea center, whereas AAV2 containing the ubiquitous promoter hybrid cytomegalovirus (CMV) enhancer/chicken-β-actin (CBA) transduced both Müller and ganglion cells in a dense circular disc centered on the fovea. With three shorter promoters—human synapsin (hSYN) and the shortened CBA and hCx36 promoters (smCBA and hCx36sh)—AAV2 produced visible transduction, as seen in fundus images, only when the retina was altered by ganglion cell loss or enzymatic vitreolysis. Conclusions. The results in the macaque suggest that intravitreal injection of AAV2 would produce high levels of gene expression at the human fovea, important in retinal gene therapy, but not in the central retina beyond the fovea. PMID:21310920

  2. Short-term intraocular pressure changes after intravitreal injection of bevacizumab in diabetic retinopathy patients

    PubMed Central

    Farhood, Qasim Kadhim; Twfeeq, Sinan Mohammad

    2014-01-01

    Background This study examined the changes in short-term intraocular pressure (IOP) in a prospective series of patients undergoing intravitreal bevacizumab injection. The aim was to evaluate the frequency and predictive factors related to intraocular pressure (IOP) elevation in patients receiving intravitreal bevacizumab. Patients and methods This study included 52 patients with diabetic retinopathy between 28 to 75 years of age with a mean age of 51 years; 30 (58%) were females, and 22 (42%) were males. All patients received bevacizumab (1.25 mg/0.05 mL) injected intravitreally in a standard fashion between May 2012 to February 2013 in the AL-Jumhoury teaching hospital. IOP was measured at baseline, 5, 10, and 30 minutes after injection using Goldman applanation tonometry. Statistics Data were analyzed using the SPSS v.12.0 for windows. Basic, demographic, and clinical data were analyzed using means, proportions, and appropriate 95% confidence intervals (CIs). Results Most patients (85%) were diagnosed with proliferative diabetic retinopathy, while 15% presented with diabetic macular edema. The mean IOP values at baseline, 5, 10, and 30 minutes after injection were 14.0 mmHg (95% CI 13.4–14.7), 36.1 mmHg (95% CI 33.5–38.6), 25.7 mmHg (95% CI 23.8–27.5), and 15.5 mmHg (95% CI 12.4–16.51), respectively. Regression analysis showed a trend toward phakic patients having higher IOP at 30 minutes. Conclusion Intravitreal injection of bevacizumab is safe with respect to short-term IOP changes, as almost all IOP returned to a safe range (<25 mmHg) within 30 minutes. Elevated IOP 30 minutes after injection only occurs rarely, so routine prophylactic use of anti-glaucoma medication is not indicated. PMID:24707164

  3. Batch-related sterile endophthalmitis following intravitreal injection of bevacizumab

    PubMed Central

    Entezari, Morteza; Ramezani, Alireza; Ahmadieh, Hamid; Ghasemi, Hassan

    2014-01-01

    Background: To report a series of patients with sterile endophthalmitis after intravitreal bevacizumab (IVB) injection from 2 different batches of bevacizumab. Materials and Methods: Records of 11 eyes with severe inflammation after IVB injections from two different batches (7 eyes from one and 4 from the other) on two separate days were evaluated. Fifteen eyes of 15 patients in one day were treated with one batch and 18 eyes of 17 patients were treated another day using another batch injected for different retinal diseases. Each batch was opened on the day of injection. We used commercially available bevacizumab (100 mg/4 ml) kept at 4°C. Severe cases with hypopyon were admitted to the ward and underwent anterior chamber and vitreous tap for direct smear and culture. Results: Pain, redness and decreased vision began after 11-17 days. All had anterior chamber and vitreous reactions and 5 had hypopyon. Antibiotics and corticosteroids were initiated immediately, but the antibiotics were discontinued after negative culture results. Visual acuity returned to pre-injection levels in 10 eyes after 1 month and only in one eye pars plana vitrectomy was performed. Mean VA at the time of presentation with inflammation (1.76 ± 0.78 logMAR) decreased significantly (P =0.008) compared to the initial mean corrected VA (1.18 ± 0.55 logMAR); however, final mean corrected VA (1.02 ± 0.48 logMAR) improved in comparison with the baseline but not to a significant level (P =0.159). Conclusions: We report a cluster of sterile endophthalmitis following intravitreal injection of bevacizumab from the same batch of bevacizumab that has a favorable prognosis. PMID:23619494

  4. Management of iatrogenic crystalline lens injury occurred during intravitreal injection.

    PubMed

    Erdogan, Gurkan; Gunay, Betul Onal; Unlu, Cihan; Gunay, Murat; Ergin, Ahmet

    2016-08-01

    To evaluate the approach to management of iatrogenic crystalline lens injury occurred during intravitreal injection (IVI). The patients who were managed operatively or followed-up without intervention after the iatrogenic lens injury due to IVI were included in the study. Capsular breaks remained either quiescent or resulted in cataract formation in the patients with inadvertent crystalline lens capsule damage. Phacoemulsification surgery was performed in patients with cataract formation with lower fluidic settings. A total of 9 cases included in the study. Seven cases underwent phacoemulsification with intraocular lens implantation. Two cases remained as quiescent lens injury during the follow-up. In 2 cases, dislocation of lens fragments occurred during phacoemulsification where pars plana vitrectomy was performed at the same session. After iatrogenic crystalline lens injury, capsular damage could remain quiescent or progress to cataract formation. Although phacoemulsification surgery can be performed with appropriate parameters, lens fragment dislocation can be observed in cases with traumatic lens damage secondary to IVI. PMID:26631401

  5. Intravitreal injection of anti-VEGF and diagnosis of primary intraocular central nervous system lymphoma.

    PubMed

    Gambrelle, J; Missotten, G; Delhoum, S; Desjardins, L

    2013-05-01

    We report a case of primary intraocular central nervous system (CNS) lymphoma in a patient previously treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections for age-related macular degeneration (AMD). An 88-year-old woman, with past medical history significant for bilateral age-related macular degeneration (AMD) treated with intravitreal ranibizumab injections for 1 year, was referred to our department for bilateral vitritis diagnosed 10 days after the last anti-VEGF injection. A complete uveitis work-up including aqueous humour analysis, brain MRI and vitreous biopsy enabled us to confirm the diagnosis of primary intraocular CNS lymphoma. To the best of our knowledge, this is the first report of the diagnosis of primary intraocular CNS lymphoma in a patient treated with anti-VEGF for AMD. The differential diagnosis of vitritis in elderly patients is relatively broad. Endophthalmitis and uveitis have been described after anti-VEGF injections. In such a situation, there is actually a risk of missing the diagnosis of intraocular lymphoma in the mistaken belief that the observed vitritis may be a reaction to administered anti-VEGFs. If no direct time-relationship with the anti-VEGF injections can be found, a classic vitritis work-up should be performed. Our observation suggests that ranibizumab, at the dosage used for AMD, does not impede the spread of CNS lymphoma in the eye nor interfere with cytological diagnosis. PMID:23306179

  6. Death by Water: Precautionary Water Submersion for Intravitreal Injection of Retinoblastoma Eyes

    PubMed Central

    Francis, Jasmine H; Xu, Xiaoliang L; Gobin, Y. Pierre; Marr, Brian P; Brodie, Scott E; Abramson, David H

    2014-01-01

    There is growing interest in intravitreal injections of chemotherapy for retinoblastoma. However, concerns for potential tumor seeding through the needle track has prompted the use of risk-reducing precautionary methods. Presented here is a novel technique, which can be easily replicated, requires minimal sophisticated equipment and with laboratory data supporting its concept. Sterile distilled water submersion for 3 minutes renders retinoblastoma cells nonviable and can be employed as a precautionary method following intravitreal injection in the technique described here. PMID:24949111

  7. Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child

    PubMed Central

    Shao, E H; Sivagnanavel, V; Dabbagh, A; Dave, R; Tempest-Roe, S; Tam, F W K; Taylor, S R

    2015-01-01

    Purpose To investigate whether intravitreal ranibizumab injections administered to a child alter systemic plasma levels of total and free VEGF 165. Methods A 9-year-old child sustained a choroidal rupture from blunt trauma. He subsequently developed a secondary choroidal neovascular membrane, which was treated with five ranibizumab injections over a period of 8 months. Peripheral venous blood samples were taken at each visit over a period of 12 months and plasma was extracted. Plasma VEGF 165 levels were determined using enzyme-linked immunosorbent assay and were assayed both pre- and post-immunodepletion to remove complexed VEGF. Results Plasma VEGF 165 levels proved labile following intravitreal injection of ranibizumab. Levels increased by 30% above baseline following the first intravitreal ranibizumab injection, but then returned to baseline despite two subsequent injections. There was then a rebound increase of 67% in total plasma VEGF levels following a further injection, which remained above baseline for 12 weeks despite two further intravitreal ranibizumab injections. Baseline levels were re-attained 26 weeks after the final injection. Conclusions These results suggest intravitreal ranibizumab injections can cause significant, multiphasic changes in systemic VEGF levels. This may be of particular clinical significance in children as VEGF is known to be vital in the development of major organs, in addition to its role in the maintenance of normal organ function in adults. PMID:25657041

  8. 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

  9. 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. PMID:26923799

  10. Evaluation of Study Participant Masking of Intravitreal Injections in a Randomized Clinical Trial

    PubMed Central

    Glassman, Adam R.; Stockdale, Cynthia R.; Beck, Roy W.; Baker, Carl; Bressler, Neil M.

    2012-01-01

    Objective To evaluate the success of masking study participants to treatment allocation using sham intravitreal injections. Methods Eyes were randomized to prompt laser plus sham injections, prompt laser plus intravitreal ranibizumab injections, deferred laser plus intravitreal ranibizumab injections, or prompt laser plus intravitreal triamcinolone injections up to every 16 weeks with sham injections intermittently. All eyes could receive treatment or sham as often as every 4 weeks. Participants with 2 study eyes had one eye randomized to sham+laser and one eye randomized to a real injection group. Sham injections were performed by pressing the syringe hub against the conjunctiva to mimic a real injection. Laser treatment was not masked. At the 1 year visit, participants were asked if they believed the injections received during the study were real, sham, or sometimes real and sometimes sham. Results Among 423 participants with one study eye, the correct assignment was stated by 10% of the sham+prompt laser group, 88% of the ranibizumab+prompt laser group, 90% of the unmasked ranibizumab+deferred laser group, and 44% of the triamcinolone+laser group. Among the 112 participants with 2 study eyes, the correct assignment was stated for 24% of the sham+prompt laser eyes. Conclusions Successful masking of an intravitreal injection can be accomplished when a sham injection procedure carefully mimics a true injection procedure. Masking appears less successful when one eye is receiving a real injection and the other eye is receiving a sham injection or an individual eye sometimes receives a real and sometimes a sham injection. PMID:22332211

  11. A protocol for the retina surgeon’s safe initial intravitreal injections

    PubMed Central

    Frenkel, Ronald EP; Haji, Shamim A; La, Melvin; Frenkel, Max PC; Reyes, Angela

    2010-01-01

    Purpose To determine the safety of a surgeon’s initial consecutive intravitreal injections using a specific protocol and to review the complications that may be attributed to the injection procedure. Design A retrospective chart review. Participants Fifty-nine patients (30 females, 29 males) received intravitreal injections of pegaptanib, bevacizumab, or ranibizumab as part of their treatment for neovascular age-related macular degeneration. The average patient age was 80 years. Twenty-two patients were diagnosed with or suspected of having glaucoma. Each patient received an average of 5.8 injections. Methods The charts of 59 patients who received a total of 345 intravitreal injections (104 pegaptanib, 74 bevacizumab, 167 ranibizumab) were reviewed. All injections were performed in an office-based setting. Povidone–iodine, topical antibiotics, and eye speculum were used as part of the pre injection procedure. Vision and intraocular pressure were evaluated immediately following each injection. Main outcome measures Incidence of post injection complications, including but not limited to endophthalmitis, retinal detachment, traumatic cataract, and vitreous hemorrhage. Results There were no cases of endophthalmitis, toxic reactions, traumatic cataracts, retinal detachment, or vitreous hemorrhage. There was one case each of lid swelling, transient floaters, retinal pigment epithelial tear, corneal edema, and corneal abrasion. There were five cases of transient no light perception following pegaptanib injections. Conclusion The incidence of serious complications was very low for the intravitreal injections given. A surgeon’s initial intravitreal injections may be performed with a very high degree of safety using this protocol. PMID:21139676

  12. LSFG findings of proliferative diabetic retinopathy after intravitreal injection of bevacizumab.

    PubMed

    Enaida, Hiroshi; Okamoto, Kenji; Fujii, Hitoshi; Ishibashi, Tatsuro

    2010-01-01

    The authors investigate the changes of chorioretinal blood flow using laser speckle flowgraphy (LSFG) in efficacy of treatment. Intravitreal bevacizumab was injected in a patient with proliferative diabetic retinopathy. LSFG measures the relative velocity index of erythrocytes (mean blur rate) in a previously confirmed area, with neovascularization elsewhere (NVE), neovascularization of the disc (NVD), and without neovascularization. The authors compared mean blur rate before and after bevacizumab injection in each area. In LSFG images, regression of blood flow was observed at the area of neovascularization sequentially as the change of color pattern. Finally, decrease of the mean blur rate of an average 32.7% was observed in the NVE area. Similarly, a reduction of 31.9% of mean blur rate was observed in the NVD area. However, in the area of without neovascularization, reduction of mean blur rate was not observed. This suggested the useful possibility of measuring chorioretinal blood flow changes by drug intervention using LSFG analysis. PMID:21117574

  13. LSFG findings of proliferative diabetic retinopathy after intravitreal injection of bevacizumab.

    PubMed

    Enaida, Hiroshi; Okamoto, Kenji; Fujii, Hitoshi; Ishibashi, Tatsuro

    2010-01-01

    The authors investigate the changes of chorioretinal blood flow using laser speckle flowgraphy (LSFG) in efficacy of treatment. Intravitreal bevacizumab was injected in a patient with proliferative diabetic retinopathy. LSFG measures the relative velocity index of erythrocytes (mean blur rate) in a previously confirmed area, with neovascularization elsewhere (NVE), neovascularization of the disc (NVD), and without neovascularization. The authors compared mean blur rate before and after bevacizumab injection in each area. In LSFG images, regression of blood flow was observed at the area of neovascularization sequentially as the change of color pattern. Finally, decrease of the mean blur rate of an average 32.7% was observed in the NVE area. Similarly, a reduction of 31.9% of mean blur rate was observed in the NVD area. However, in the area of without neovascularization, reduction of mean blur rate was not observed. This suggested the useful possibility of measuring chorioretinal blood flow changes by drug intervention using LSFG analysis. PMID:22785537

  14. Retinal tears and rhegmatogenous retinal detachment after intravitreal injections: its prevalence and case reports

    PubMed Central

    Karabag, Revan Yildirim; Parlak, Melih; Cetin, Gölgem; Yaman, Aylin; Osman Saatci, A.

    2015-01-01

    Purpose To report the prevalence of postoperative retinal tear or rhegmatogenous retinal detachment secondary to intravitreal injections. Methods Surgical and medical records of patients who received intravitreal injections at the practice of a single retina specialist from January 2004 to May 2013 and who were followed for at least 6 months were investigated retrospectively. Results During the study period, a total of 3,907 intravitreal injections were performed in 1,049 eyes of 784 patients (416 males [47%]). The mean number of injections per eye was 3.72 ± 3.43 (range, 1–22). The mean age of the participants was 67.03 ± 13.56 (range, 5–94 years). The mean follow-up time was 31.98 ± 22.86 months (range, 6–144 months). Retinal break or rhegmatogenous retinal detachment occurred in 3 injections of 3 eyes, yielding an overall prevalence of 0.077% per injection and 0.29% per eye. Conclusions Retinal tear and rhegmatogenous detachment are rare complications of intravitreal injection. Precautions should be taken especially in patients having predisposing conditions, such as high myopia, or any other vitreoretinal disorders. PMID:27330458

  15. 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

  16. Intravitreal injection of methotrexate in an experimental rabbit model: Determination of pharmacokinetics

    PubMed Central

    Ozkan, Ebru Bener; Ozcan, Altan A; Alparslan, Nazan

    2011-01-01

    Purpose: To investigate the pharmacokinetics of intravitreally administered methotrexate. Materials and Methods: Twenty-one New Zealand white rabbits were used in the study. The pharmacokinetics of intravitreally injected 800 μg/0.1 ml of methotrexate was investigated. Intravitreal concentration of the drug was measured at seven different times, in six eyes at each occasion, on a total of 42 eyes of 21 rabbits from a period of 30 minutes to 72 hours. Results: The volume of distribution was calculated as 1.33 ml following intravitreal injection of 800 μg methotrexate. Vitreous concentrations of the drug were found to be decreasing related to the specific mathematical equation; drug concentration= 1426.73 e-0.1182(time) and remained over effective dose by 81 hours with a half life of 5.9 hours. Conclusions: These findings evidenced those vitreous levels of methotrexate at various time intervals after 800 μg intravitreal injections which formulated a mathematical equation for calculation of vitreous level of the drug at each hour. PMID:21586839

  17. 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

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

    PubMed

    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

  19. Serial Intravitreal Bevacizumab Injections Slow the Progression of Radiation Maculopathy Following Iodine-125 Plaque Radiotherapy

    PubMed Central

    Stacey, Andrew W.; Demirci, Hakan

    2016-01-01

    Background and Objective: To assess the outcomes of intravitreal bevacizumab injection in the management of radiation maculopathy secondary to plaque radiotherapy, and to identify optimal treatment strategies. Study Design: A retrospective review of all choroidal melanoma patients at one referral center who were treated with plaque radiotherapy, subsequently developed radiation maculopathy, and received intravitreal bevacizumab. Results: A total of 31 patients were identified. The mean visual acuity decreased three Snellen lines in the year leading up to the first bevacizumab injection. After initiating injection therapy, the mean visual acuity remained stable for 9 months. The change in visual acuity of patients who received injections within 90 days of previous injections was significantly better than the visual acuity of those who received injections more than 90 days apart (p=0.0003). Patients who demonstrated late-phase macular leakage on fluorescein angiography at the time of the first bevacizumab injection had better long-term visual acuity outcomes than patients who had no evidence of macular leakage (average of one line improvement of vision vs. ten line loss of vision, p=0.03). Conclusions: Intravitreal bevacizumab injection was effective in stabilizing visual acuity in patients with radiation maculopathy. Patients benefited most from injections administered every 90 days or sooner. Fluorescein angiography can help identify patients who will respond favorably to treatment. PMID:27053973

  20. 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. PMID:26357547

  1. Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice

    PubMed Central

    Powner, Michael B.; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

    2015-01-01

    Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of “whitening” of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. PMID:26226015

  2. Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

    PubMed

    Jo, Dong Hyun; Park, Sung Wook; Cho, Chang Sik; Powner, Michael B; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

    2015-01-01

    Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. PMID:26226015

  3. 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. PMID:26004219

  4. 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

  5. Effect of Posterior Subtenon Triamcinolone Acetonide Injection on Diabetic Macular Edema Refractory to Intravitreal Bevacizumab Injection

    PubMed Central

    Kim, Min Woo; Moon, Haein; Yang, Sung Jae

    2016-01-01

    Purpose To evaluate the effects of posterior subtenon triamcinolone acetonide injection on refractory diabetic macular edema (DME) after intravitreal bevacizumab (IVB) injection failure. Methods Patients with DME and central subfield thickness (CST) >300 µm who did not respond to IVB injections were retrospectively included. Specifically, we enrolled patients who were diagnosed with refractory DME and who experienced an increase in CST after 1 to 2 IVB injections or no decrease after ≥3 consecutive IVB injections. One clinician injected 20 mg of triamcinolone acetonide into the posterior subtenon space. All patients received ophthalmic examinations at baseline and at 2, 4, and 6 months post-baseline. Examinations included Snellen visual acuity, intraocular pressure, and spectral-domain optical coherence tomography. Results Forty eyes of 34 patients were included. The average baseline CST was 476 µm. The average CST decreased to 368 µm at 2 months, 374 µm at 4 months, and 427 µm at 6 months (p < 0.001 for all results, Wilcoxon signed-rank test). The average intraocular pressure increased from 15.50 to 16.92 mmHg at 2 months but decreased to 16.30 mmHg at 4 months and 15.65 mmHg at 6 months. Logarithm of the minimum angle of resolution visual acuity improved from 0.56 to 0.50 at 2 months (p = 0.023), 0.50 at 4 months (p = 0.083), and 0.48 at 6 months (p = 0.133, Wilcoxon signed-rank test). No complications were detected. Conclusions Posterior subtenon triamcinolone acetonide is an effective and safe treatment for reducing CST in DME refractory to IVB. PMID:26865800

  6. Effect of dorzolamide-timolol fixed combination prophylaxis on intraocular pressure spikes after intravitreal bevacizumab injection

    PubMed Central

    Ozcaliskan, Sehnaz; Ozturk, Faruk; Yilmazbas, Pelin; Beyazyildiz, Ozlem

    2015-01-01

    AIM To evaluate the effect of topical dorzolamide-timolol fixed combination prophylaxis on short term intraocular pressure (IOP) changes in patients who had intravitreal bevacizumab injection. METHODS One hundred and fifty one eyes of 151 patients which were followed up in retina clinic in Ulucanlar Eye Training and Research Hospital were evaluated in this study. Patients were divided into two groups. Group 1 consists of 75 patients who had topical dorzolamid-timolol medication two hours before injection; while Group 2 consists of 76 patients without prophylaxis. Demographic data, IOP measurements prior to the injection and one, thirty and sixty minutes and twenty-four hours after the injection were recorded. The data were analyzed using SPSS software version 15.0 (SPSS Inc., Chicago, IL, USA). RESULTS There were no significant difference between two groups in age, gender distrubition and indications for injections. The mean IOPs in Groups 1 and 2 prior to the injection (T0) were 17.84±0.43 and 18.15±0.43 mm Hg, one minute after the injection (T1) were 29.75±1.6 and 34.44±1.59 mm Hg, 30min after the injection (T30) were 20.06±0.6 and 21.71±0.59 mm Hg respectively. The mean IOPs were 18.26±0.56 mm Hg in Group 1 and 19.78±0.56 mm Hg in Group 2 sixty minutes after the injection (T60). All IOP values after the injection were compared between two groups, there was a significant difference between two groups only on T1; one minute after the injection (P=0.04). There were a statiscially significant difference between the baseline values and other recorded values; except on T60, in Groups 1 and 2 (P<0.05). CONCLUSION After intravitreal bevacizumab injection; we observe a transient IOP elevation which normalizes about one hour after intravitreal injection. In patients who had topical dorzolamid-timolol combination prophylaxis before injections, a significant decrease is seen in IOP spikes due to this injection. The appropiate approach will monitor IOP after

  7. Repeated Intravitreous Ranibizumab Injections for Diabetic Macular Edema and the Risk of Sustained IOP Elevation or Ocular Hypotensive Treatment

    PubMed Central

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

    2015-01-01

    Importance For the management of retinal disease, use of intravitreous injections of anti-vascular endothelial growth factor has increased. Recent reports have suggested that this therapy may cause persistent intraocular pressure (IOP) elevation and potentially increase the risk of glaucoma in patients with retinal disease. Objective To assess the risk of sustained IOP elevation or the need for IOP-lowering treatments in eyes with diabetic macular edema following repeated intravitreous injections of ranibizumab. Main Outcome Measure(s) The cumulative probability of sustained IOP elevation, defined as an IOP of at least 22 mmHg and an increase of at least 6 mmHg from baseline at 2 consecutive visits, or initiation or augmentation of ocular hypotensive therapy, through 3 years of follow up. Design, Setting, and Participants An exploratory analysis was conducted within a Diabetic Retinopathy Clinical Research Network randomized clinical trial. Of 486 participants (582 eyes) with center-involved diabetic macular edema and no pre-existing open-angle glaucoma, 260 eyes were randomly assigned to receive sham injection plus focal/grid laser; 322 to ranibizumab plus deferred or prompt focal/grid laser. Results The mean baseline IOP in both treatment groups was 16±3 mmHg (range 5–24 mm Hg). The cumulative probability of sustained IOP elevation or initiation or augmentation of ocular hypotensive therapy by 3 years, after repeated ranibizumab injections, was 9.5% in the ranibizumab plus prompt or deferred laser group versus 3.4% in the sham plus laser group (difference = 6.1%, 99% CI: −0.2% to 12.3%; hazard ratio = 2.9, 99% CI: 1.0 to 7.9, P = 0.01). The distribution of IOP and the change in IOP from baseline at each visit through 3 years was similar in each group. Conclusions In eyes with center-involved diabetic macular edema and no prior open angle glaucoma, repeated intravitreous injections of ranibizumab may increase the risk of sustained IOP elevation or the need

  8. [Ocular hypertension after intravitreal steroid injections: Clinical update as of 2015].

    PubMed

    Dot, C; El Chehab, H; Russo, A; Agard, E

    2015-09-01

    Intravitreal injections are a therapeutic delivery method best suited to the treatment of retinal diseases. Recent years have been marked by the use of anti-VEGF agents as well as the arrival of sustained-release corticosteroid implants in France, replacing triamcinolone acetonide. A common complication of IVT steroids is secondary ocular hypertension (OHT) resulting from increased outflow resistance. This article summarizes current understanding. OHT induced by topical steroids has been described for 60 years. Intravitreal use also shows a temporary effect if the exposure is short, dose dependence, and varying incidence depending on the drug used. Sustained release formulations and discontinuing treatment have reduced the risk of induced OHT. Risk factors that induce OHT must be clearly identified prior to an injection. Most cases of OHT can be controlled medically, although differences exist between different drugs. In cases where it cannot be controlled, removal of the implant, selective laser trabeculoplasty, and filtration surgery can be discussed. PMID:26099427

  9. Pituitary Apoplexy After Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitor: A Novel Complication

    PubMed Central

    Kasl, Rebecca A.; Kistka, Heather M.; Turner, Justin H.; Devin, Jessica K.; Chambless, Lola B.

    2015-01-01

    Pituitary adenomas are common in the general population. They can be complicated by intratumoral hemorrhage, otherwise known as apoplexy, which frequently presents with neurologic deficits that may necessitate urgent surgical decompression. Many risk factors for pituitary apoplexy have been suggested in the literature. We present a case of symptomatic apoplexy in a woman following the intravitreal administration of the vascular endothelial growth factor (VEGF) inhibitor ranibizumab. Ophthalmoplegia resolved and visual acuity significantly improved following gross total resection of the tumor via an endoscopic endonasal surgical approach. The association between intravitreal injection of a VEGF inhibitor and pituitary apoplexy has not been previously described, but physicians performing these procedures should be aware of this potential complication. PMID:26623228

  10. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26325627

  12. Surgical Removal of Retained Subfoveal Perfluorocarbon Liquid through a Therapeutic Macular Hole with Intravitreal PFCL Injection and Gas Tamponade

    PubMed Central

    Kim, Jae Min; Park, Kyu Hyung; Chung, Hum

    2013-01-01

    We report two cases of surgical removal of a retained subfoveal perfluorocarbon liquid (PFCL) bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade. Two patients underwent pars plana vitrectomy with PFCL injection for rhegmatogenous retinal detachment. In both cases, a retained subfoveal PFCL bubble was noticed postoperatively by funduscopy and optical coherence tomography. Both patients underwent surgical removal of the subfoveal PFCL through a therapeutic macular hole and gas tamponade. The therapeutic macular holes were completely closed by gas tamponade and the procedure yielded a good visual outcome (best-corrected visual acuity of 20 / 40 in both cases). In one case, additional intravitreal PFCL injection onto the macula reduced the size of the therapeutic macular hole and preserved the retinal structures in the macula. Surgical removal of a retained subfoveal PFCL bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade provides an effective treatment option. PMID:24082781

  13. Intravitreal Injection of Dexamethasone Implant in Serous Macular Detachment Associated with Waldenström's Disease

    PubMed Central

    Fenicia, Vito; Balestrieri, Marco; Perdicchi, Andrea; Maraone, Giorgia; Recupero, Santi Maria

    2013-01-01

    Purpose To evaluate the efficacy of one intravitreal injection of dexamethasone (Ozurdex®; Allergan, Inc., Irvine, Calif., USA) in serous macular detachment (SMD) of one eye, associated with bilateral central retinal vein occlusion (CRVO) in a patient affected by Waldenström's macroglobulinemia (WM). Patients and Methods A female patient, affected by WM, complained of a progressive decrease in visual acuity, mainly in the left eye (LE). SMD in the LE associated with bilateral CRVO was diagnosed. One intravitreal injection of dexamethasone was administered in the LE and the patient was tested 1, 2, and 6 months after the injection. Results 1, 2, and 6 months after the injection, the spectral domain optical coherence tomography (SD-OCT) showed a progressive slight reduction of foveal thickness that was not related to any improvement of visual function. Conclusions Treatment with dexamethasone (Ozurdex) induced a progressive slight reduction of SMD but no improvement of visual acuity, and it is possible that this is related to the condition of hematic hyperviscosity that is present in WM. PMID:24019788

  14. Clinical effect of intravitreous injection of triamcinolone acetonide in treating cystoid macular edema.

    PubMed

    Yan, P S; Qian, C; Wan, G M; Wang, W Z; Dong, Y; Li, F Z

    2016-01-01

    Cystoid macular edema (CME), a commonly seen sign for multiple fundus diseases, is able to induce visual deterioration. The incidence rate of CME is constantly increasing; however, the existing clinical treatments cannot achieve satisfactory curative effects. To explore the curative effect of intravitreous injection of triamcinolone acetonide (TA) in treating CME, this study carried out a clinical test on 39 patients (42 eyes) from The First Affiliated Hospital of Zhengzhou University who developed CME induced by central retinal vein occlusion (CRVO). All 42 eyes received intravitreous injection of 40 mg/ml TA (0.1 ml) and then were followed up for 11-23.5 months. Eyes were examined by slit-lamp microscope, fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) and best corrected visual acuity (BCVA), and intraocular pressure (IOP) of those eyes were detected before and after treatment. Average vision of eyes was 0.1 before treatment, and the vision improved in one month (vision ≥ 0.2: 100%; vision ≥ 0.5: 42.9%) and three months (vision ≥ 0.2: 64.3%; vision ≥ 0.5: 21.4%) after treatment; but as time went on, the vision of some patients declined; at the last follow-up, patients with vision ≥ 0.2 accounted for 28.6% and those with vision ≥0.5 accounted for 7.1%; compared to before treatment, 71.4% patients had improved vision and the remaining 28.6% had declined vision. Some patients were observed with high IOP during treatment, and 7 eyes were found with secondary cataract in posterior capsule of lens at the last follow-up. Intravitreous injection of triamcinolone acetonide proved to have significant short-term curative effect on CEM which is non-sensitive to conventional therapies, but it is likely to induce high IPO and posterior capsular opacification. PMID:27049093

  15. Streptococcus Endophthalmitis Outbreak after Intravitreal Injection of Bevacizumab: One-year Outcomes and Investigative Results

    PubMed Central

    Goldberg, Roger A.; Flynn, Harry W.; Miller, Darlene; Gonzalez, Serafin; Isom, Ryan F.

    2013-01-01

    Purpose To report the one-year clinical outcomes of an outbreak of Streptococcus endophthalmitis after intravitreal injection of bevacizumab, including visual acuity outcomes, microbiological testing and compound pharmacy investigations by the Food and Drug Administration (FDA). Design Retrospective consecutive case series. Participants 12 eyes of 12 patients who developed endophthalmitis after receiving intravitreal bevacizumab prepared by a single compounding pharmacy. Methods Medical records of patients were reviewed; phenotypic and DNA analyses were performed on microbes cultured from patients and from unused syringes. An inspection report by the FDA based on site-visits to the pharmacy that prepared the bevacizumab syringes was summarized. Main Outcome Measures Visual acuity, interventions received, time-to-intervention; microbiological consistency; FDA inspection findings. Results Between July 5 and July 8, 2011, 12 patients developed endophthalmitis after intravitreal bevacizumab from syringes prepared by a single compounding pharmacy. All patients received initial vitreous tap and injection, and eight (67%) subsequently underwent pars plana vitrectomy (PPV). After twelve months follow-up, outcomes have been poor: 7 patients (58%) required evisceration or enucleation, and only one patient regained pre-injection visual acuity. Molecular testing using real time polymerase chain reaction, partial sequencing of the groEL gene, and multilocus sequencing of 7 housekeeping genes confirmed the presence of a common strain of Streptococcus mitis/oralis in vitreous specimens and seven unused syringes prepared by the compounding pharmacy at the same time. An FDA investigation of the compounding pharmacy noted deviations from standard sterile technique, inconsistent documentation, and inadequate testing of equipment required for safe preparation of medications. Conclusions In this outbreak of endophthalmitis, outcomes have been generally poor and PPV did not improve

  16. Management of cataract caused by inadvertent capsule penetration during intravitreal injection of ranibizumab.

    PubMed

    Saeed, Muhammad Usman; Prasad, Som

    2009-11-01

    We describe an approach to phacoemulsification of complicated cataract with preexisting posterior capsule tear caused by an intravitreal injection. Careful preoperative planning and attention to fluidics, low bottle height, appropriate incisions, careful hydrodelineation without hydrodissection, avoidance of nuclear rotation, and use of a dispersive ophthalmic viscosurgical device to tamponade vitreous allows safe phacoemulsification with secure posterior chamber intraocular lens implantation. Biaxial microincision cataract surgery can achieve efficient removal of the lens matter without rotating the nucleus, reducing the chance of capsule tear extension and loss of nuclear fragments into the posterior pole. PMID:19878815

  17. Intravitreal vascular endothelial growth factor (VEGF) inhibitor injection in unrecognised early pregnancy.

    PubMed

    Kianersi, Farzan; Ghanbari, Heshmatollah; Naderi Beni, Zahra; Naderi Beni, Afsaneh

    2016-10-01

    The use of intravitreal vascular endothelial growth factor (VEGF) inhibitor medications has widened considerably to include indications affecting females of reproductive age. Our patient was inadvertently exposed to bevacizumab within the first trimester when placental growth and fetal organogenesis take place and patient suffered pregnancy loss. There is insufficient information to suggest that such use is safe, nor is there definitive evidence to suggest that it causes harm. We advise that ophthalmologists discuss pregnancy with women of childbearing age undergoing intraocular anti-VEGF injections and in pregnant woman counselling is needed to explain the potential risks and benefits. PMID:27251054

  18. CMV retinitis after intravitreal triamcinolone acetonide injection in a patient with Behçet's uveitis.

    PubMed

    Tugal-Tutkun, Ilknur; Araz, Bilge; Cagatay, Atahan

    2010-10-01

    We report the case of a patient with Behçet's uveitis who developed cytomegalovirus (CMV) retinitis after intravitreal triamcinolone acetonide (IVTA) injection. We reviewed the patient's chart for the purpose of this report. An IVTA injection was performed for treatment of severe panuveitis in the left eye of a 30-year-old male patient with Behçet's disease. Systemic treatment included high dose corticosteroid and azathioprine. Fourteen weeks after IVTA, extensive areas of necrotizing retinitis developed in the left eye. Polymerase chain reaction of serum and vitreous samples was positive for CMV DNA. Serum anti-CMV IgG was positive, IgM was negative, anti-HIV antibody was negative, complete blood count was normal, and CD4 count was 1,060 cells/μl. The patient responded well to intravitreal ganciclovir injection performed twice and intravenous ganciclovir treatment administered for five weeks. Local immunosuppression with IVTA may cause CMV retinitis. Awareness of this serious complication is important for correct diagnosis and treatment. PMID:20033756

  19. 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.

  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. PMID:19408003

  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. 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

  3. 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

  4. Intravitreal injection

    MedlinePlus

    ... disorder that slowly destroys sharp, central vision Macular edema: Swelling or thickening of the macula, the part ... 29, 2013. Mitchell P, Wong TY, Diabetic Macular Edema Treatment Guideline Working Group. Management paradigms for diabetic ...

  5. Therapeutic effect of intravitreal injections of ranibizumab for the treatment of macular choroidal neovascularization caused by pathological myopia

    PubMed Central

    JI, LEIBING; LV, WENJUAN; XIAO, YUN; XU, ZHENGHUA; ZHANG, XIAOLING; ZHANG, WEI

    2015-01-01

    The aim of the present study was to evaluate the clinical efficacy and safety of intravitreal ranibizumab injections for the treatment of macular choroidal neovascularization (CNV) caused by pathological myopia. Between one and four intravitreal injections of ranibizumab were administered to 61 eyes from 61 patients who were diagnosed with macular CNV caused by pathological myopia. Following injection, the best-corrected visual acuity (BCVA), central macular thickness (CMT) and fundus fluorescein angiography (FFA) findings were evaluated monthly for a period of 6 months. Among the 61 eyes, 10 eyes received one injection, 44 received two injections, six received three injections and one received four injections (average, 1.97 injections). The BCVA was 0.02±0.01 prior to treatment and 0.30±0.03 subsequent to treatment, and this difference was statistically significant (P<0.01). The CMT was reduced by an average of 45.1 µm. Regarding the FFA results, 56 eyes had no CNV fluorescence leakage and five eyes had CNV fluorescence leakage following treatment; however, the intensity of CNV fluorescence leakage in the five eyes following treatment was lower than that prior to treatment. As a treatment for pathological myopia-induced macular CNV, intravitreal injections of ranibizumab may improve eyesight as well as the macular retinal tissue structure; thus, this is a safe and effective treatment method. PMID:26622450

  6. 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. PMID:27108911

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

    PubMed Central

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

    2016-01-01

    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. PMID:27460435

  8. 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. PMID:27460435

  9. Intravitreal Injection of Dexamethasone Implant and Ranibizumab in Cystoid Macular Edema in the Course of Irvine-Gass Syndrome

    PubMed Central

    Fenicia, Vito; Balestrieri, Marco; Perdicchi, Andrea; MauriziEnrici, Maurizio; DelleFave, Martina; Recupero, Santi Maria

    2014-01-01

    Purpose To evaluate the efficacy of 2 dexamethasone intravitreal implants and 1 ranibizumab intravitreal injection after a bilateral postoperative complication of cataract surgery as pseudophakic cystoid macular edema. Patients and Methods A 70-year-old male patient with systemic hypertension developed a progressive cystoid macular edema (CME) in both eyes starting between 10 and 20 days after cataract surgery. Two intravitreal dexamethasone implants and 1 ranibizumab injection were administered; first in the right eye (RE) and then in the left eye (LE). The patient was checked for 1 whole week and then once a month for 5 months after the injections. Results One month after the first dexamethasone implant in his RE, the spectral domain optical coherence tomography (SD-OCT) showed a progressive reduction of the foveal thickness until a complete resolution of the CME occurred, which was associated with an improvement of visual acuity. After 3 months, the SD-OCT showed a relapse of the CME, which was then treated with 1 injection of ranibizumab. One month after this injection, there was a complete resolution of the CME. A new CME in his RE was diagnosed 2 months after the last ranibizumab injection; it was treated with a new dexamethasone implant. A complete resolution of the CME was obtained; a normal foveal profile was still present 5 months after the last injection, and the best-corrected visual acuity was 20/20. His LE developed a CME 40 days after surgery. One intravitreal injection of ranibizumab was first administered in his LE, with a complete resolution of the CME at SD-OCT 2 weeks later. As observed in his RE, 40 days after the ranibizumab injection, there was a relapse of the CME that was treated with 1 intravitreal injection of dexamethasone implant. Five months later, the patient showed a worsening of the CME, but it was completely resolved with a second dexamethasone injection. After 3 months, the foveal thickness was back to normal with a BCVA of 20

  10. Ganglion Cell Complex Evaluation in Exudative Age-Related Macular Degeneration after Repeated Intravitreal Injections of Ranibizumab.

    PubMed

    Perdicchi, Andrea; Peluso, Giacomo; Iacovello, Daniela; Balestrieri, Marco; Delle Fave, Martina; Abdolrahimzadeh, Solmaz; Scuderi, Gian Luca; Fenicia, Vito; Recupero, Santi Maria

    2015-01-01

    Purpose. To detect the effects of intravitreal ranibizumab injections on GCC in patients with wet AMD. Methods. 32 wet AMD eyes were selected and submitted at three ranibizumab injections. RTVue-OCT GCC and MM5 protocol were performed before treatment and twenty days after each injection. Results. At baseline mean GCC thickness was 93.9 ± 18.5 μm. Twenty days after each intravitreal injection it was, respectively, 85.8 ± 10.1, 86.5 ± 9.3, and 91.1 ± 11.5 μm, without statistical significance. A significant improvement in visual acuity (P = 0.031) and a reduction of mean foveal (P = 0.001) and macular thickness (P = 0.001) were observed. Conclusion. The clinical results confirm therapeutic efficacy of intravitreal injections of ranibizumab in wet AMD. A contemporary not statistically significant reduction of GCC thickness suggests that the loading phase of ranibizumab does not have any toxic effects on ganglion cell complex. PMID:26167478

  11. Ganglion Cell Complex Evaluation in Exudative Age-Related Macular Degeneration after Repeated Intravitreal Injections of Ranibizumab

    PubMed Central

    Perdicchi, Andrea; Peluso, Giacomo; Iacovello, Daniela; Balestrieri, Marco; Delle Fave, Martina; Abdolrahimzadeh, Solmaz; Scuderi, Gian Luca; Fenicia, Vito; Recupero, Santi Maria

    2015-01-01

    Purpose. To detect the effects of intravitreal ranibizumab injections on GCC in patients with wet AMD. Methods. 32 wet AMD eyes were selected and submitted at three ranibizumab injections. RTVue-OCT GCC and MM5 protocol were performed before treatment and twenty days after each injection. Results. At baseline mean GCC thickness was 93.9 ± 18.5 μm. Twenty days after each intravitreal injection it was, respectively, 85.8 ± 10.1, 86.5 ± 9.3, and 91.1 ± 11.5 μm, without statistical significance. A significant improvement in visual acuity (P = 0.031) and a reduction of mean foveal (P = 0.001) and macular thickness (P = 0.001) were observed. Conclusion. The clinical results confirm therapeutic efficacy of intravitreal injections of ranibizumab in wet AMD. A contemporary not statistically significant reduction of GCC thickness suggests that the loading phase of ranibizumab does not have any toxic effects on ganglion cell complex. PMID:26167478

  12. 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

  13. 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

  14. Injectable formulations for an intravitreal sustained-release application of a novel single-chain VEGF antibody fragment.

    PubMed

    Asmus, Lutz R; Grimshaw, John P A; Richle, Philipp; Eicher, Barbara; Urech, David M; Gurny, Robert; Möller, Michael

    2015-09-01

    Sustained-release formulations of a single-chain anti-VEGF-A antibody fragment were investigated in vitro toward their potential use for intravitreal applications. The hydrophobic polyester hexylsubstituted poly(lactic acid) (hexPLA) was selected as the sustained-release excipient for its biodegradability and semi-solid aggregate state, allowing an easy and mild formulation procedure. The lyophilized antibody fragment ESBA903 was micronized and incorporated into the liquid polymer matrix by cryo-milling, forming homogeneous and injectable suspensions. The protein showed excellent compatibility with the hexPLA polymer and storage stability at 4°C for 10 weeks. Additionally, hexPLA shielded the incorporated active substance from the surrounding medium, resulting in a better stability of ESBA903 inside the polymer than after its release in the buffer solution. Formulations of ESBA903 with hexPLA having drug loadings between 1.25% and 5.0% and polymer molecular weights of 1500 g/mol, 2500 g/mol, 3500 g/mol and 5000 g/mol were investigated regarding their in vitro release. All formulations except with the highest molecular weight formed spherical depots in aqueous buffer solutions and released the antibody fragment for at least 6-14 weeks. The polymer viscosity derived from the molecular weight strongly influenced the release rate, while the drug loading had minor influence, allowing customization of the release profile and the daily drug release. Size exclusion chromatography and SDS-PAGE revealed that the antibody fragment structure was kept intact during incorporation and release from the liquid matrix. Furthermore, the released protein monomer maintained its high affinity to human VEGF-A, as measured by surface plasmon resonance analysis. Formulations of ESBA903 in hexPLA meet the basic needs to be used for intravitreal sustained-release applications in age-related macular degeneration treatment. PMID:25779352

  15. The discrepancy between central foveal thickness and best corrected visual acuity in cystoid macular edema secondary to central retinal vein occlusion after intravitreal lucentis® injection.

    PubMed

    Hua, Rui; Li, Chenyan; Hu, Yuedong; Chen, Lei

    2015-06-01

    Cystoid macular edema is a common retinal disorder with the potential for significant vision-related morbidity, and intravitreal lucentis(®) injection is confirmed to be an effective therapy approach. In the present study, we investigated the discrepancy between central foveal thickness and best corrected visual acuity in such lesions and infered that intravitreal lucentis(®) injection may help the visual function, related to the renewal of cells. PMID:25818575

  16. Intravitreal Ranibizumab Injection as an Adjuvant in the Treatment of Neovascular Glaucoma Accompanied by Vitreous Hemorrhage after Diabetic Vitrectomy

    PubMed Central

    Shen, Xi; Chen, Yanwei; Wang, Yanuo; Yang, Lu; Zhong, Yisheng

    2016-01-01

    Purpose. To determine the efficacy of intravitreal ranibizumab injection as adjuvant therapy in the treatment of neovascular glaucoma (NVG) accompanied by postvitrectomy diabetic vitreous hemorrhage (PDVH). Methods. Eighteen NVG patients (18 eyes) accompanied by PDVH were enrolled in this prospective, monocenter, 12-month, interventional case series. The consecutive 18 patients with an IOP ≥ 25 mmHg despite being treated with the maximum medical therapy were treated with intravitreal ranibizumab injections. Vitreous surgery or/with Ahmed valve implantation were indicated if no clinical improvement in vitreous haemorrhage and uncontrolled IOP was shown. Results. Ten patients got clear vitreous and controlled IOP only with 2.7 ± 1.8 injections of ranibizumab without additional surgery. Vitrectomy or/with Ahmed valve implantation was administered in the other 8 eyes due to uncontrolled VH and IOP. At follow-up month 12, all the 18 eyes gained clear vitreous. At month 12 BCVA improved significantly compared to baseline. The baseline and follow-up at month 12 IOP/medication usage were 36.7 ± 8.1 mmHg on 3.4 ± 0.7 medications and 16.2 ± 4.9 mmHg on 0.67 ± 0.77 medications, respectively. Conclusions. The findings suggest that intravitreal ranibizumab injection as adjuvant therapy for treatment of NVG accompanied by PDVH may be safe and potentially effective. This clinical trial is registered with NCT02647515. PMID:27293875

  17. Clinical research on intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease.

    PubMed

    Yan, Ying; Wang, Tao; Cao, Jing; Wang, Meng; Li, Fenghua

    2015-07-01

    This paper aimed to explore clinically curative effect of intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new vessel (CNV) received and cured in the hospital from February 2010 to February 2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month and a total of 2-3 times. Results of patients' vision and fluorescence fundus angiography (FFA), optical coherence tomography (OCT) before and after treatment were compared and curative effects were evaluated. Vision of 349 eyes (89.49%) improved obviously with the average of more than 2 lines, patient's intraocular pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes (6.67%) was stable before the treatment and without any changes after the treatment, the situation of fundus got better without increased IOP; vision of 15 eyes (3.85%) decreased to some extent, and the symptoms eased slightly after symptomatic treatment. In the 1st day after intravitreal injection, best-corrected visual acuity increased to 0.239±0.175, best-corrected visual acuity in 1 m was 0.315±0.182, in 3m continuously climbed to 0.350±0.270, and in 6 m was 0.362±0.282. Compared with vision before injection, t value was t=3.184, t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000) respectively, and all P were less than 0.01. Furthermore, the difference was significant if a=0.01, which could confirm that 1m best corrected visual acuity of patients after intravitreal injection improved clearly in combination with before injection and 3m and 6 m visions enhanced constantly after injection. To sum up, intravitreal injection of bevacizumab in treating ocular fundus disease improves patient's vision

  18. Muscarinic receptor antagonist and an alpha-adrenergic agonist are required in combination to provide stable mydriasis following intravitreal injection in mice

    PubMed Central

    Mojumder, Deb Kumar

    2010-01-01

    Tropicamide (muscarinic receptor antagonist) and phenylephrine (α-adrenergic receptor agonist) are commonly used to dilate the pupils by topical application. These two eye drops are often used, singly or in combination, to dilate the pupil and perform acute light-evoked physiological experiments (electroretinography, for example), before and after intravitreal injections of pharmacological agents, as an assay for their affect on retinal activity. This study wanted to determine whether treatment with one of these drugs, or with both, is most effective in maintaining mydriasis after intravitreal injections. Changes in pupillary dilation before and after intravitreal injection of balanced salt solution (0.5 µl) were recorded. Phenylephrine (α-adrenergic agonist) and tropicamide (muscarinic agonist) when combined, but not singly, produced full and stable pupillary dilation following intravitreal injections. Re-instillation of topical mydriatics after intravitreal injections was required for maximal pupillary dilation. A combination of a muscarinic receptor antagonist and an alpha-adrenergic agonist is required for stable mydriasis following intravitreal injection. PMID:20852745

  19. Two Cases of Acute Abdomen after an Intravitreal Injection of Bevacizumab

    PubMed Central

    Onoda, Yasutaka; Shiba, Tomoaki; Hori, Yuichi; Maeno, Takatoshi; Takahashi, Mao

    2015-01-01

    We report on a patient with ischemic colitis and another with paralytic ileus, both of whom experienced an acute abdomen after intravitreal injection of bevacizumab (IVB). Case 1 was a 78-year-old woman. Her medical history included surgery for colon carcinoma 10 years earlier. The patient developed acute severe abdominal pain and nausea the day after IVB for retinal vein occlusion with macular edema, and massive lower gastrointestinal bleeding occurred. Ischemic colitis was diagnosed. Case 2 was a 64-year-old man who presented with neovascular glaucoma with proliferative diabetic retinopathy. We performed vitreous surgery on the 9th day after IVB, and we reperformed IVB at the end of the vitreous surgery. On the first postoperative day, severe abdominal distension, vomiting and abdominal pain were observed, and paralytic ileus was diagnosed. It is possible that gastrointestinal disorders are induced after IVB, depending on the patient's background, including for example severe diabetes or a history of surgery for gastrointestinal cancer. Thus, ophthalmologists should apply alternative therapies instead of IVB to patients with severe diabetes mellitus or a history of gastrointestinal cancer. PMID:25960733

  20. Two cases of acute abdomen after an intravitreal injection of bevacizumab.

    PubMed

    Onoda, Yasutaka; Shiba, Tomoaki; Hori, Yuichi; Maeno, Takatoshi; Takahashi, Mao

    2015-01-01

    We report on a patient with ischemic colitis and another with paralytic ileus, both of whom experienced an acute abdomen after intravitreal injection of bevacizumab (IVB). Case 1 was a 78-year-old woman. Her medical history included surgery for colon carcinoma 10 years earlier. The patient developed acute severe abdominal pain and nausea the day after IVB for retinal vein occlusion with macular edema, and massive lower gastrointestinal bleeding occurred. Ischemic colitis was diagnosed. Case 2 was a 64-year-old man who presented with neovascular glaucoma with proliferative diabetic retinopathy. We performed vitreous surgery on the 9th day after IVB, and we reperformed IVB at the end of the vitreous surgery. On the first postoperative day, severe abdominal distension, vomiting and abdominal pain were observed, and paralytic ileus was diagnosed. It is possible that gastrointestinal disorders are induced after IVB, depending on the patient's background, including for example severe diabetes or a history of surgery for gastrointestinal cancer. Thus, ophthalmologists should apply alternative therapies instead of IVB to patients with severe diabetes mellitus or a history of gastrointestinal cancer. PMID:25960733

  1. [Anti-infectious activity of intravitreal injectable voriconazole microspheres on experimental rabbit fungal endophthalmitis of Aspergillus fumigatus].

    PubMed

    Yang, Li-Na; Xin, Meng; Wu, Xiang-Gen; Jiang, Hao-Ran

    2010-06-01

    The therapeutic effect of sustained intravitreal injectable voriconazole microspheres (VCZ-MS) on an experimental endophthalmitis of Aspergillus fumigatus was investigated. VCZ-MS was prepared successfully and its physico-chemical property was also evaluated. Right eyes of albino rabbits were infected with an intravitreal injection of 1 000 CFU x mL(-1) of susceptible Aspergillus fumigatus. All fungal endophthalmitis models were randomly divided into five groups 48 hours later: Group A is control group with no treatment; in group B, vitrectomy was performed combined with intravitreal 3 times injections of 100 microg x 0.1 mL(-1) voriconazole every other day. In group C, D and E, vitrectomy was performed combined with intravitreal injection of 0.5 mg, 1.0 mg and 1.5 mg VCZ-MS respectively. The treatment effect was assessed by slit lamp and indirect ophthalmoscope funduscopy examination, using clinical grading system of inflammation in the anterior chamber and the vitreous opacity. The optical microscopy revealed that microspheres obtained from the experiment design were opaque, discrete and spherical particles with smooth surfaces. The drug content and encapsulation efficiency of microspheres were 29.94% and 73.5%, respectively. Endophthalmitis occurred in all eyes of group A, and rapidly developed to panophthalmitis. The inflammation grade of group B, C, D or E was lower than that of group A (P < 0.05). The grade of vitreous opacity in group C, D, E is lower than group B (P < 0.05). Two eyes in group C developed to panophthalmitis. But in group D and E, all eyes whose inflammation was controlled had no recurrence with vitreous clear. Histopathological examination showed normal structures in the cured eyes, while most uncured eyes were atrophic and with eyeball destroyed. So, it can be safely concluded that the curative effect of intravitreal VCZ-MS is significantly better than that of routine intraocular injection of voriconazole. The optimal dose is the one

  2. Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

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

    2014-01-01

    Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and

  3. 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

  4. Effects of intravitreal injection of netrin-1 in retinal neovascularization of streptozotocin-induced diabetic rats

    PubMed Central

    Yu, Yao; Zou, Jing; Han, Yun; Quyang, Luowa; He, Hui; Hu, Peihong; Shao, Yi; Tu, Ping

    2015-01-01

    Background In a previous study, we confirmed that netrin-1 acts as an antiangiogenic factor by inhibiting alkali burn-induced corneal neovascularization in rats. Here, we continue working on the role of netrin-1 in retinal neovascularization. Methods Using an in vitro angiogenesis assay, we detected the effects of netrin-1 on human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion at concentrations of 0.1 μg/mL or 5 μg/mL. We intravitreally injected 0.1 μg/mL or 5 μg/mL netrin-1 into streptozotocin-induced rats to assess retinal neovascularization using retinal electrophysiology and electroretinography, enzyme-linked immunosorbent assay, fundus fluoresce in angiography, measurement of inner blood retinal barrier, retinal hematoxylin-eosin staining, and retinal flat-mount fluorescence assays. Results Human umbilical vein endothelial cell tube formation, viability and proliferation, migration, and invasion were upregulated by netrin-1 at a concentration of 0.1 μg/mL (P<0.05), while 5 μg/mL netrin-1 had an opposite effect (P<0.05) in our in vitro angiogenesis assay. Retinal electrophysiology testing revealed that intravitreal injection of netrin-1 affected the amplitude of a- and b-waves (a-wave: 0.1 μg/mL netrin-1 =17.67±3.39 μm, 5 μg/mL netrin-1 =28.50±1.31 μm, phosphate-buffered saline [PBS]-treated =17.67±3.39 μm; b-wave: 0.1 μg/mL netrin-1 =44.67±4.80 μm, 5 μg/mL netrin-1 =97.17±9.63 μm, PBS-treated =44.67±4.80 μm) and the expression of VEGF-A (no-treatment rats, 9.29±0.80 pg/mL; PBS-treated rats, 19.64±3.77 pg/mL; 0.1 μg/mL netrin-1 treated rats, 21.37±3.64 pg/mL; 5 μg/mL netrin-1 treated rats, 9.85±0.54 pg/mL, at 6 weeks after induction). By comparing fluoresce in angiography, level of inner blood retinal barrier breakdown (% of control), retinal hematoxylin-eosin staining, and collagen-IV fluorescence assays in the retinas of PBS-treated rats, netrin-1 was found to suppress and

  5. A systematic review and meta-analysis comparing intravitreal ranibizumab with bevacizumab for the treatment of myopic choroidal neovascularisation

    PubMed Central

    Loutfi, M.; Siddiqui, M.R.S.; Dhedhi, A.; Kamal, A.

    2014-01-01

    Intravitreal injections of ranibizumab (IVR) and bevacizumab (IVB) have both been used as treatments for myopic choroidal neovascularisation. We aimed to produce a meta-analysis of published literature comparing IVR with IVB for the treatment of myopic choroidal neovascularisation, by searching electronic databases from January 1950 to March 2013. Our search produced three suitable studies that reported on 117 patients in total. The results of the meta-analysis demonstrated that the mean number of lines improvement after IVR appeared better compared with IVB [fixed effects model: SMD = 0.46, 95% CI (0.09, 0.83), z = 2.44, p = 0.01]. The number of patients who had a greater than 3 line improvement was similar between groups [fixed effects model: RR = 0.95, 95% CI (0.67, 1.32), z = 0.33, p = 0.74]. At follow up there was no difference in number of those who had an absence of leakage [fixed effects model: RR = 1.04, 95% CI (0.93, 1.16), z = 0.64, p = 0.52]. There was no statistical significance between the two groups in relation to the number of injections [random effects model: SMD = −0.25, 95% CI (−1.12, 0.61), z = 0.57, p = 0.57]. Early evidence therefore suggests that intravitreal injections of ranibizumab are comparable to intravitreal injections of bevacizumab in the treatment of myopic choroidal neovascularisation. Both treatments result in a statistically significant increase in visual acuity with high numbers of patients maintaining stable vision. Further studies are still needed to strengthen results. PMID:25892935

  6. 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

  7. 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

  8. 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

  9. A Case of Sustained Intraocular Pressure Elevation after Multiple Intravitreal Injection of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration

    PubMed Central

    Matsubara, Hisashi; Miyata, Ryohei; Kobayashi, Maki; Tsukitome, Hideyuki; Ikesugi, Kengo; Kondo, Mineo

    2016-01-01

    Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop. PMID:27462248

  10. 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

  11. Placenta Growth Factor in Eyes with Neovascular Glaucoma Is Decreased after Intravitreal Ranibizumab Injection

    PubMed Central

    Zhou, Minwen; Wang, Jiawei; Wang, Wei; Huang, Wenbin; Ding, Xiaoyan; Zhang, Xiulan

    2016-01-01

    Purpose To evaluate changes in the concentrations of placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A) in aqueous humor of patients with neovascular glaucoma (NVG) before and after an intravitreal injection of ranibizumab (IVR) and to determine the underlying correlation between the levels. Methods The prospective interventional comparative study involved 20 eyes of 20 patients with surgery-required advanced NVG and 20 control subjects from January 2013 to November 2013. The NVG eyes received the IVR treatment before glaucoma surgery. Aqueous humor was collected at the time of the IVR injection (pre- IVR) and at the time of antiglaucomatous surgery (post-IVR). Aqueous humor was also collected at the time of cataract surgery in normal control. Aqueous humor and plasma VEGF-A and PlGF levels were measured with an enzyme-linked immunosorbent assay methods, respectively. Results The mean aqueous humor PlGF and VEGF-A concentrations in the pre-IVR eyes were significantly higher than in those of the control subjects (p<0.001), whereas the plasma levels showed no significant difference. There was a statistically significant correlation between the aqueous humor PlGF and the VEGF-A concentration (r = 0.612, p = 0.003). The mean aqueous humor PlGF in the post-IVR eyes dramatically decreased from 1078.36 ± 755.83 to 177.64 ± 151.73 pg/mL (p<0.001). The VEGF-A level showed a similar trend from 3697.64 ± 2104.47 pg/mL to 183.54 ± 130.35 pg/mL (p<0.001). Conclusions Aqueous humor concentrations of VEGF-A and PlGF were significantly elevated in the eyes with NVG, and there was a positive correlation between the levels. After an IVR treatment, VEGF-A and PlGF were significantly decreased in NVG eyes. PMID:26785251

  12. G-quartet oligonucleotide mediated delivery of proteins into photoreceptors and retinal pigment epithelium via intravitreal injection.

    PubMed

    Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2016-04-01

    There is currently no available method to efficiently deliver proteins across the plasma membrane of photoreceptor or retinal pigment epithelium (RPE) cells in vivo. Thus, current clinical application of recombinant proteins in ophthalmology is limited to the use of proteins that perform their biological function extracellularly. The ability to traverse biological membranes would enable the mobilization of a significantly larger number of proteins with previously well characterized properties. Nucleolin is abundantly present on the surface of rapidly dividing cells including cancer cells. Surprisingly, nucleolin is also present on the surface of photoreceptor cell bodies. Here we investigated whether nucleolin can be utilized as a gateway for the delivery of proteins into retinal cells following intravitreal injection. AS1411 is a G-quartet aptamer capable of targeting nucleolin. Subsequent to intravitreal injection, fluorescently labeled AS1411 localized to various retinal cell types including the photoreceptors and RPE. AS1411 linked to streptavidin (a ∼50 kDa protein) via a biotin bridge enabled the uptake of Streptavidin into photoreceptors and RPE. AS1411-Streptavidin conjugate applied topically to the cornea allowed for uptake of the conjugate into the nucleus and cytoplasm of corneal endothelial cells. Clinical relevance of AS1411 as a delivery vehicle was strongly indicated by demonstration of the presence of cell surface nucleolin on the photoreceptors, inner neurons and ganglion cells of human retina. These data support exploration of AS1411 as a means of delivering therapeutic proteins to diseased retina. PMID:26923800

  13. 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. PMID:27229628

  14. 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

  15. 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. PMID:10431798

  16. A single injection of intravitreal ranibizumab in the treatment of choroidal neovascularisation secondary to optic nerve head drusen in a child

    PubMed Central

    Alkin, Zeynep; Ozkaya, Abdullah; Yilmaz, Ihsan; Yazici, Ahmet Taylan

    2014-01-01

    Optic nerve head drusen are acellular, calcified deposits which may be found in buried or exposed drusen form. Choroidal neovascularisation secondary to optic nerve head drusen is rarely seen in childhood. This case report summarises the clinical and therapeutic outcomes of a 13-year-old girl with unilateral choroidal neovascularisation secondary to optic nerve head drusen. The patient was successfully treated with a single intravitreal ranibizumab injection. After a month from the injection the visual acuity increased dramatically and maintained at the same level during 9 months of follow-up time. There was no complication related to the injection. PMID:24792030

  17. Pharmacokinetic and Pharmacodynamic Properties of Anti-VEGF Drugs After Intravitreal Injection.

    PubMed

    Semeraro, Francesco; Morescalchi, Francesco; Duse, Sarah; Gambicorti, Elena; Cancarini, Anna; Costagliola, Ciro

    2015-01-01

    Subretinal neovascularization and pathologic ocular angiogenesis are common causes of progressive, irreversible impairment of central vision, and dramatically affect quality of life. Anti-vascular endothelial growth factor (anti-VEGF) therapy has improved the quality of life for many patients with age-related macular degeneration, diabetic retinopathy, and other ocular diseases involving neovascularization and edema. In these pathologies, the inhibition of intraocular VEGF is the only therapy that can preserve vision. Four anti-VEGF drugs are currently used to treat ocular neovascularization; pegaptanib, ranibizumab, and aflibercept have been approved for this condition, while bevacizumab can be used off-label. Anti-VEGF therapy is administered regularly for many months or years because its suspension or discontinuation may cause recurrence of neovascularization. On the other hand, VEGF is necessary for the survival of retinal and choroidal endothelial cells. Experimental studies in animal models have shown that local inhibition of VEGF causes thinning and atrophy of the choriocapillaris and degeneration of photoreceptors, primarily cones. These studies combined with clinical experience indicated that prolonged VEGF inhibition could impair retinal function. Moreover, anti-VEGF compounds can cross the blood-retina barrier, enter the systemic circulation, and inhibit serum VEGF. Since circulating VEGF protects blood vessel integrity, prolonged anti-VEGF treatment could induce thromboembolic adverse events from vascular causes such as heart attack and stroke, and even death. The ocular dosing regimen and systemic toxicity of anti-VEGF compounds are therefore central concerns. A better understanding of this topic requires knowledge of the metabolism, tissue distribution, and clearance of anti-VEGF compounds. This manuscript reviews the properties of anti-VEGF compounds following intravitreal administration. PMID:26424177

  18. A safety audit of the first 10 000 intravitreal ranibizumab injections performed by nurse practitioners

    PubMed Central

    Simcock, P; Kingett, B; Mann, N; Reddy, V; Park, J

    2014-01-01

    Purpose To evaluate the safety of a nurse practitioner (NP)-delivered injection service for the treatment of wet age-related macular degeneration (wAMD) with ranibizumab. Methods An evaluation of medical staffing resources for providing an injection service for wAMD highlighted difficulties covering lists. An alternative strategy of an NP-delivered injection service was evaluated. Two suitable NPs with previous extensive experience in minor surgical procedures were identified. The department's senior vitreo-retinal consultant supervised the NP's training programme. A prospective safety audit was conducted for the first 5.5 years of the service. Results The NPs administered 10 006 injections in the first 5.5 years of the service (1 May 2008 to 8 October 2013). This represented 84.1% of the total injections performed during this period. Four patients developed presumed infectious endophthalmitis (1 was culture positive and 3 were culture negative). The incidence of post-injection endophthalmitis was 0.04%. There was no evidence of lens touch, retinal detachment, or systemic thrombo-embolic events. Conclusions Carefully selected and well-trained NPs are capable of delivering a safe and effective wAMD injection treatment service. This work demonstrates how such a service can be established and provides safety data that other units can use as a benchmark when evaluating their own practice. PMID:25033899

  19. Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats.

    PubMed

    Mitsuhashi, Junko; Morikawa, Shunichi; Shimizu, Kazuhiko; Ezaki, Taichi; Yasuda, Yoshiko; Hori, Sadao

    2013-01-01

    A single intravitreal injection of erythropoietin (EPO) (50 ng/eye) or phosphate-buffered saline was administered to 5-week-old Sprague-Dawley rats at the onset of diabetes mellitus (DM) to determine and evaluate the protective effect of EPO on retinal microvessels. DM was induced by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Morphological changes in microvessels in flat retinal preparations were evaluated during the subsequent 4 weeks by three-dimensional imaging of all blood vessels stained with fluorescein isothiocyanate-conjugated tomato lectin, following immunofluorescence techniques. No marked differences were observed in the shape or density of retinal vessels and the number of retinal capillary branches of the four groups [control, EPO, DM, and DM/EPO] up to 4 weeks after STZ administration. We also observed unique type IV collagen-positive filamentous structures that lacked both cellular elements and blood circulation (lectin-/type IV+ acellular strands), suggesting regressed vessel remnants. The lectin-/type IV+ acellular strands were detected soon after the onset of DM in the diabetic rats, and the number of these structures increased in the DM group (P < 0.01). A single intravitreal injection of EPO caused a significant reduction in the number of lectin-/type IV+ acellular strands to levels observed in the control group. However, the lectin-/type IV+ acellular strands were observed in the central area of the retina near the optic disc in all four groups. Intravitreal injection of EPO resulted in downregulation of the EPO receptor, vascular endothelial growth factor (VEGF), and VEGF receptor at 4 weeks. We conclude that EPO may play a primary role against the progression of diabetic retinopathy by reducing blood vessel degeneration at a very early disease stage. PMID:23178551

  20. Intravitreal Injection of a Rho-Kinase Inhibitor (Fasudil) for Recent-Onset Nonarteritic Anterior Ischemic Optic Neuropathy.

    PubMed

    Sanjari, Nasrin; Pakravan, Mohammad; Nourinia, Ramin; Esfandiari, Hamed; Hafezi-Moghadam, Ali; Zandi, Souska; Nakao, Shintaro; Shah-Heidari, Mohamamad-Hassan; Jamali, Arsia; Yaseri, Mehdi; Ahmadieh, Hamid

    2016-06-01

    This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes received a 0.025 mg/0.05 mL IVF. Functional and structural outcomes were assessed 1 and 3 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measured, with mean deviation (MD) index of the VF test and peripapillary retinal nerve fiber layer thickness as secondary measures. There was a statistically significant improvement in the patients' BCVA 1 and 3 months following IVF; BCVA improved from 1.69 ± 0.55 logMAR at baseline to 0.98 ± 0.47 and 0.93 ± 0.51 logMAR at 1 and 3 months, respectively (P = .004). The change in BCVA was not significant between month 1 and month 3 (P = .22). Peripapillary retinal nerve fiber layer thickness decreased from 173.5 ± 29.28 µm in the baseline evaluation to 85.8 ± 8.8 µm at 1 month, and 62.9 ± 5.97 µm at 3 months (P = .003). MD values changed from 24.60 ± 3.80 to 21.0 ± 6.10 and 20.5 ± 6.50 at 1 and 3 months, respectively (P = .007 and .005, respectively). This pilot study suggests that IVF may be an effective treatment for patients with recent-onset NAION. Larger studies are required to establish the therapeutic role of fasudil for NAION. PMID:26444290

  1. Evaluation of contrast sensitivity after single intravitreal triamcinolone injection for macular edema secondary to branch retinal vein occlusion.

    PubMed

    Aras Ogreden, Tulin; Alkin, Zeynep; Ozkaya, Abdullah; Ibrahim Demirkale, Halil; Perente, Irfan; Aras, Cengiz

    2013-01-01

    Purpose. To evaluate visual acuity (VA), contrast sensitivity (CS), and central retinal thickness (CRT) after intravitreal triamcinolone acetonide (IVT) injection for macular edema secondary to branch retinal vein occlusion (BRVO). Methods. In this prospective study, a total of 21 eyes of 21 patients were included. VA, CS, and CRT were assessed at baseline and at 1, 3, and 6 months after a single IVT injection. Results. Mean age was 64.57 ± 8.34 years. The mean baseline VA (LogMAR) increased from 1.11 ± 0.63 to 0.55 ± 0.39 (P < 0.001), 0.60 ± 0.40 (P < 0.001), and 0.78 ± 0.39 (P = 0.07) at 1, 3, and 6 months, respectively. The mean baseline CS (log CS) at 1 meter improved from 0.66 ± 0.49 to 1.11 ± 0.32 (P < 0.001), 0.99 ± 0.38 (P < 0.001), and 0.72 ± 0.37 (P = 0.8) at 1, 3, and 6 months, respectively. The mean baseline CS (log CS) at 3 meters improved from 0.34 ± 0.41 to 0.74 ± 0.41 (P < 0.001), 0.64 ± 0.44 (P = 0.036), and 0.46 ± 0.49 (P = 0.8) at 1, 3, and 6 months, respectively. The mean baseline CRT decreased from 511 ± 146 μm to 242 ± 119 μm, 277 ± 131 μm, and 402 ± 166 μm at 1, 3, and 6 months after IVT (P < 0.001 for each). Conclusion. Single IVT injection improved VA and CS and reduced CRT at 1 and 3 months of treatment. VA and CS returned to baseline levels at 6 months. PMID:24563794

  2. 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

  3. 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

  4. Effective Treatment with Intravitreal Injection of Bevacizumab for Exudative Retinal Detachment Secondary to Choroidal Metastasis of Non-Small Cell Lung Carcinoma

    PubMed Central

    Yasui, Hirotoshi; Sato, Kazuhide; Takeyama, Yoshihiro; Nishihara, Hiroaki; Maeda, Matsuyoshi; Gonda, Hideo; Suzuki, Ryujiro

    2015-01-01

    Patient: Male, 68 Final Diagnosis: Non-small cell lung cancer Symptoms: — Medication: — Clinical Procedure: TBLB • PET • OCT • fluorescence angiography Specialty: Oncology Objective: Challenging differential diagnosis Background: Visual disturbance caused by cancer metastasis from other organs is one of the largest challenges to cancer patients’ quality of life (QOL). Lung cancer is the most frequent primary site of choroidal metastasis in men, but improvement of visual disturbance has not always been emphasized in lung cancers. Recently intravitreal bevacizumab is a newer modality being tried for local control of choroidal metastases. Case Report: A 68-year-old man was admitted the hospital with complaint of visual disturbance in his left eye. He was diagnosed with lung adenocarcinoma cT2N0M1b (OSS, OTH) stage IV. The ophthalmologic evaluation showed exudative fluid, which caused retinal detachment under the retina. Fluorescence angiography showed granular hyperfluorescence with leakage consistent with a tumor. He received radiotherapy for bone metastasis and systematic chemotherapy with carboplatin, pemetrexed, and bevacizumab, as well as intravitreal injection of bevacizumab 1.25 mg to improve the visual disturbance. His visual symptom and retinal detachment improved until he died. An autopsy revealed that the metastatic lesion in his left eye was totally cured macroscopically and microscopically. Conclusions: We report a case of exudative retinal detachment secondary to a metastatic choroidal tumor from lung adenocarcinoma, which was treated with chemotherapy and intravitreal injection of bevacizumab. Although he finally died of lung cancer, he maintained his visual QOL and autopsy revealed complete cure of the choroidal metastasis. PMID:26460101

  5. 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

  6. Short-term intraocular pressure trends following intravitreal ranibizumab injections for neovascular age-related macular degeneration—the role of oral acetazolamide in protecting glaucoma patients

    PubMed Central

    Murray, C D; Wood, D; Allgar, V; Walters, G; Gale, R P

    2014-01-01

    Purpose To determine the effect of oral acetazolamide on lowering the peak and duration of intraocular pressure (IOP) rise in glaucoma and glaucoma suspect patients, following intravitreal injection of ranibizumab for neovascular age-related macular degeneration. Methods The study was an open-label, parallel, randomised, controlled trial (EudraCT Number: 2010-023037-35). Twenty-four glaucoma or glaucoma suspect patients received either 500 mg acetazolamide or no treatment 60–90 min before 0.5 mg ranibizumab. The primary outcome measure was the difference in IOP immediately after injection (T0) and 5, 10, and 30 min following injection. ANCOVA was used to compare groups, adjusting for baseline IOP. The study was powered to detect a 9-mm Hg difference at T0. Results The IOP at T0 was 2.3 mm Hg higher in the non-treated group (mean 44.5 mm Hg, range (19–86 mm Hg)) compared with the treated group (mean 42.2 mm Hg, range (25–58 mm Hg)), but was not statistically significant after adjusting for baseline IOP (P=0.440). At 30 min, IOP was 4.9 mm Hg higher in the non-treated group (mean 20.6 mm Hg, range (11–46 mm Hg)) compared with the treated group (mean 15.7 mm Hg, range (8–21 mm Hg)). This was statistically significant after adjusting for baseline IOP (P=0.013). Conclusions Although the primary end points were not reached, 500 mg oral acetazolamide, 60–90 min before intravitreal injection, results in a statistically significant reduction in IOP at 3O min post injection. Prophylactic treatment may be considered as an option to minimise neuro-retinal rim damage in high-risk glaucoma patients who are most vulnerable to IOP spikes and undergoing repeated intravitreal injections of ranibizumab. PMID:25081290

  7. Retinal Function and Morphology in the Rabbit Eye after Intravitreal Injection of the TNF Alpha Inhibitor Adalimumab

    PubMed Central

    Ghosh, Fredrik; Andréasson, Sten; Ponjavic, Vesna

    2014-01-01

    Aim To study the effects of the tumor necrosis factor alpha inhibitor adalimumab on rabbit retina after injection into the vitreous body. Methods Forty-eight rabbits of mixed strain (9–12 months old, weighing ≈ 3.5 kg) were randomized into four groups. Adalimumab was injected at one of two concentrations (1.25 mg or 2.5 mg) into the eyes of two groups, and balanced salt solution into the eyes of the third group. The fourth group acted as controls. Full-field electroretinography (ffERG) was performed before injection and 1 and 6 weeks post-injection. At 6 weeks post-injection the rabbits were euthanized and the sectioned retinas were studied. Retinal histology was studied with hematoxylin–eosin staining. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Müller cells. Results No significant difference in ffERG amplitudes or implicit times was observed between the four groups at any time point. Histological and immunohistochemical findings were similar in all groups. Conclusions Injection of adalimumab into the vitreous body of healthy rabbits, at doses up to 2.5 mg, does not appear to be toxic to the rabbit retina. PMID:24897597

  8. INTRAVITREAL DICLOFENAC VERSUS INTRAVITREAL TRIAMCINOLONE FOR THE TREATMENT OF UVEITIC CYSTOID MACULAR EDEMA.

    PubMed

    Soheilian, Masoud; Eskandari, Armen; Ramezani, Alireza; Rabbanikhah, Zahra; Esmaeilpour, Nasim F; Soheilian, Roham

    2013-04-11

    PURPOSE:: To compare the effect of intravitreal diclofenac (IVD) versus intravitreal triamcinolone (IVT) on refractory uveitic cystoid macular edema. METHODS:: In this pilot, randomized, clinical trial, 15 eyes were randomly assigned to IVD group, patients (8 eyes) who received a single intravitreal injection of diclofenac (500 μg/0.1 mL), and IVT group (7 eyes) patients who received a single intravitreal injection of triamcinolone (2 mg). Change in best-corrected visual acuity in logarithm of the minimum angle of resolution at Week 36 was the primary outcome measure. Secondary outcomes included changes in best-corrected visual acuity (BCVA) at 12 weeks and 24 weeks, central macular thickness, macular leakage, and potential injection-related complications. RESULTS:: In the IVD group, BCVA was more than the baseline values in 4 eyes at 36 weeks; however, within-group analysis disclosed no statistically significant changes in the mean BCVA in this group. Nonetheless, in the IVT group, mean BCVA improved significantly at 12, 24, but not at 36 weeks compared with the baseline values. It was 0.86 ± 0.37 at baseline and 0.63 ± 0.48, 0.62 ± 0.42, and 0.43 ± 0.49 logarithm of the minimum angle of resolution at 12, 24, and 36 weeks, respectively. Mean central macular thickness diminished also significantly only in the IVT group. Nevertheless, comparing the mean BCVA and central macular thickness changes, macular leakage, and the occurrence of any injection-related complications, no significant difference was observed between the groups at any of the follow-up visits. CONCLUSION:: This pilot study demonstrated the superiority of IVT over IVD in the treatment of refractory uveitic cystoid macular edema regarding both functional and anatomical outcomes. Further studies are warranted to confirm potential benefit of IVD observed in this study. PMID:23584700

  9. One-year outcome of intravitreal aflibercept injection for age-related macular degeneration resistant to ranibizumab: rapid morphologic recovery and subsequent visual improvement

    PubMed Central

    Hirakata, Toshiaki; Fujinami, Kaoru; Watanabe, Ken; Sasaki, Mariko; Noda, Toru; Akiyama, Kunihiko

    2016-01-01

    Objective To describe the 1-year efficacy of aflibercept in Japanese patients with age-related macular degeneration (AMD) who were resistant to ranibizumab treatment. Design Retrospective case series. Participants Fourteen consecutive eyes of 14 patients with AMD were enrolled who had no substantial response or developed resistance to intravitreal ranibizumab injections. Methods All patients were subcategorized into one of two subtypes of AMD: seven patients with occult choroidal neovascularization (CNV) and seven with polypoidal choroidal vasculopathy (PCV). Serial intravitreal aflibercept (IVA) injections were administered. Comprehensive ophthalmic examinations, including optical coherence tomography, were conducted at baseline and at follow-up examinations at 1, 3, 6, and 12 months after the initial IVA injection. The best-corrected visual acuity converted to logarithm of the minimum angle of resolution (logMAR) and central macular thickness (CMT) at each follow-up visit were compared with the baseline values. The anatomic response was also assessed with absorption or reduction of fluid in the subretina or subretinal pigment epithelial space. Results The logMAR best-corrected visual acuity improved significantly at 3, 6, and 12 months in the total cohort: at 3 and 6 months in patients with occult CNV and at 3 and 12 months in patients with PCV. The CMT decreased significantly at all follow-up visits in the total cohort as well as in both subtypes, except for the CMT at 6 months in PCV patients. The anatomic improvement was also demonstrated in all cases, and pigment epithelial detachments tended to be resolved more rapidly in patients with PCV than in patients with occult CNV. Conclusion Conversion to IVA was effective in patients with AMD resistant to ranibizumab, showing rapid morphologic improvement. The logMAR visual acuity was raised significantly within 12 months, and the clinical course of visual acuity improvement may differ according to the AMD subtypes

  10. 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.

  11. 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

  12. 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. PMID:26440056

  13. 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

  14. 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. PMID:25810725

  15. 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

  16. Intravitreal injection of ranibizumab using a pro re nata regimen for age-related macular degeneration and vision-related quality of life

    PubMed Central

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

    2014-01-01

    Background The purpose of this study was to assess visual function and vision-related quality of life after intravitreal injection of ranibizumab (IVR) using a pro re nata regimen for the treatment of age-related macular degeneration. Methods A prospective study of 54 eyes in 54 patients scheduled to undergo IVR for the treatment of exudative age-related macular degeneration was performed. A self-administered, 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was completed before and 3 and 12 months after the initial IVR treatment. We evaluated logMAR visual acuity and NEI VFQ-25 scores preoperatively and postoperatively. Further, associations between the changes in NEI VFQ-25 scores and patient characteristics were investigated at 12 months. Results Postoperative best-corrected visual acuity improved significantly when compared with the preoperative visual acuity throughout the 12-month period (P<0.05 at 3 and 12 months, respectively). On the other hand, IVR treatment significantly improved the postoperative NEI VFQ-25 mean composite score at both 3 and 12 months (P<0.05, respectively). Better visual acuity at 12 months was associated with a greater improvement in NEI VFQ-25 score at 12 months (P<0.05). Conclusion IVR was well tolerated and improved vision in these patients with age-related macular degeneration, as evaluated at one-year follow-up examinations. IVR also enabled good subjective perception, as indicated by higher composite NEI VFQ-25 scores. Maintaining good visual acuity may be an important factor for improving vision-related quality of life. PMID:25228787

  17. Pharmacokinetics and Safety of Intravitreal Caspofungin

    PubMed Central

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

    2014-01-01

    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. PMID:25246398

  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. Outcomes after Intravitreal Bevacizumab versus Laser Photocoagulation for Retinopathy of Prematurity: A 5-Year Retrospective Analysis

    PubMed Central

    Hwang, Christopher K.; Hubbard, G. Baker; Hutchinson, Amy K.; Lambert, Scott R.

    2014-01-01

    Purpose To determine the relative effectiveness, major complications, and refractive errors associated with intravitreal bevacizumab (IVB) versus panretinal photocoagulation (PRP) to treat Type 1 retinopathy of prematurity (ROP). Subjects Consecutive infants with Type 1 ROP who received either IVB or PRP between January 2008 and December 2012 and had at least six months of follow-up. Design Retrospective case series. Methods The data from infants treated with either IVB or PRP for Type 1 ROP between January 2008 and December 2012 were recorded from two medical centers in Atlanta, Georgia. Main Outcome Measures Recurrence rate, complication rate, refractive error. Results A total of 54 eyes (28 patients) with Type 1 ROP were evaluated: 22 eyes (11 patients) received IVB, and 32 eyes (17 patients) received PRP. Among the 22 eyes treated with IVB, 16 eyes had Zone I ROP and 6 eyes had posterior Zone II ROP. The number of Zone I and Zone II ROP eyes treated with PRP were 5 and 27 eyes, respectively. Mean gestational age, birth weight, postmenstrual age at the initial treatment, and follow-up period for the infants receiving IVB were 24.2 weeks, 668.1 grams, 35.1 weeks, and 21.7 weeks, respectively, and for the infants receiving PRP were 24.8, 701.4 grams, 36.1 weeks, and 34.5 weeks, respectively. ROP recurred in 3/22 (14%) IVB-treated eyes and in 1/32 (3%) PRP-treated eyes. None of IVB-treated eyes progressed to retinal detachment or developed macular ectopia. Only one eye went on to retinal detachment and five eyes developed macular ectopia in PRP-treated eyes. Mean spherical equivalent and postgestational age at the last refraction for IVB-treated eyes were −2.4 D and 22.4 months, respectively, and for PRP-treated eyes were −5.3 D and 37.1 months, respectively. Mean spherical equivalent for Zone I ROP eyes treated with IVB and PRP were −3.7 D and −10.1 D, respectively, and for Zone II ROP eyes were 0.6 D and −4.7 D, respectively. Conclusions Both IVB and

  1. 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

  2. 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

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

    PubMed Central

    Liu, Xiang-Dong; Zhou, Xiao-Dong; Wang, Zhi; Shen, Hong-Jie

    2014-01-01

    AIM To further evaluate the efficacy and safety of intravitreal bevacizumab (IVB) versus macular photocoagulation (MPC) in treatment of diabetic macular edema (DME) by Meta-analysis. METHODS Pertinent publications were identified through systemic searches of PubMed, Medline, EMBASE, and the Cochrane Controlled Trials Register up to 30 November, 2013. Changes in central macular thickness (CMT) in µm and best-corrected visual acuity (BCVA) in logMAR equivalents were extracted at 1, 3, 6, 12 and 24mo after initial treatment, and a Meta-analysis was carried out to compare results between groups receiving IVB and MPC. RESULTS Five randomized controlled trial (RCTs) and one high-quality comparative study were identified and included. Our Meta-analysis revealed that both IVB and MPC resulted in the improvements of CMT and BCVA in eyes with DME at 1mo after initial treatment, with IVB being significantly superior to MPC (P=0.01 and 0.02, respectively). The improvements of both measure outcomes at 3, 6, 12 and 24mo after treatment did not vary significantly between the IVB groups and MPC groups (CMT at 3mo, P=0.85; at 6mo, P=0.29; at 12mo, P=0.56; at 24mo, P=0.71; BCVA at 3mo, P=0.31; at 6mo, P= 0.30; at 12mo, P=0.23; at 24mo, P=0.52). However, the number of observed adverse events was low in all studies. CONCLUSION Current evidence shows IVB treatment trends to be more effective in improvements of macular edema and vision in eyes with DME at an earlier follow up (1mo) compared with MPC. At other time, both interventions have comparable efficacy without statistical significances. PMID:25540764

  4. 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

  5. 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

  6. Intravitreal ketorolac for the treatment of chronic cystoid macular edema after cataract surgery

    PubMed Central

    Tsilimbaris, Miltiadis K; Tsika, Chrysanthi; Kymionis, George D

    2016-01-01

    Purpose To report two cases of chronic postoperative cystoid macular edema, resistant to topical therapy, treated with consecutive intravitreal injections of ketorolac tromethamine. Methods Four daily intravitreal injections of 500 μg/0.05 mL of ketorolac were given to each patient. Complete clinical examination and OCT were performed before every injection, 1, 2, 3 weeks, and 1, 3, and 6 months after the last injection. Fluorescein angiography was performed at baseline examination, 1, 3, and 6 months after the last injection. Results In both cases, the edema regressed and visual acuity increased. At 6 months after the last injection, the leakage was significantly reduced at the fluorescein angiography. Discussion Both cases responded favorably to the consecutive intravitreal administration of ketorolac tromethamine. The long-lasting remission of the macular edema in these chronic cases underlines the therapeutic potential of these agents when delivered intravitreally. PMID:26929630

  7. 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

  8. Determination of doxorubicin in rabbit ocular tissues and pharmacokinetics after intravitreal injection of a single dose of doxorubicin-loaded poly-beta-hydroxybutyrate microspheres.

    PubMed

    Hu, Tao; Le, Qihua; Wu, Zhiyi; Wu, Wei

    2007-01-01

    A validated HPLC method was developed for the quantification of doxorubicin in rabbit ocular tissues using solid phase extraction and ultraviolet detection. Chromatographic separation of doxorubicin in various ocular tissues was performed on a C18 column. The mobile phase was composed of 0.2 M KH2PO4 buffer solution, acetonitrile and triethylamine in volumetric ratio of 70/30/0.2, adjusted to pH 4.0 with orthophosphoric acid. The calibration curve was linear over the range of 0.03-10, 0.03-10, 0.05-10 and 0.05-10 microg/ml in vitreous body, iris, retina/choroids and sclera, respectively. The intra-day and inter-day precisions in all ocular tissues were smaller than 4.95% and 5.73%, and the accuracies were about 100%. The extraction recoveries of doxorubicin in all of the ocular tissues were between 83.47% and 96.33%. After intravitreal administration of doxorubicin-loaded poly-beta-hydroxybutyrate microspheres, doxorubicin level in ocular tissues was much lower than that for administration of free doxorubicin, which was helpful to reduce the associated toxicity to surrounding tissues. Doxorubicin was detectable even after tens of days in the studied ocular tissues. PMID:16884884

  9. Intravitreal pegaptanib for the treatment of ischemic diabetic macular edema

    PubMed Central

    Kiire, Christine A; Morjaria, Rupal; Rudenko, Anna; Fantato, Alexina; Smith, Lewis; Smith, Amy; Chong, Victor

    2015-01-01

    Purpose Pegaptanib has been shown to be effective in treating diabetic macular edema (DME). In the original Phase II/III trial, however, patients with macular ischemia were excluded. In this study, we treated patients with ischemic DME. Methods Macular ischemia was defined as a 30% increase in the area of the foveal avascular zone (FAZ) at 45 seconds on fundus fluorescein angiography. In addition, the participants had diffuse foveal-involving DME with a central subfield thickness (CST) of >300 μm on spectral-domain optical coherence tomography. Five intravitreal pegaptanib injections were given 6 weeks apart. The final study visit was 6 weeks after the fifth injection. The primary outcome was change in the size of FAZ. Secondary outcomes were change in best-corrected visual acuity (BCVA) and the change in CST. Results Thirty participants were enrolled. Three were unable to complete the full course of treatment. Their outcomes were carried forward for the first part of this analysis. There was no statistically significant change in the mean size of the FAZ from baseline to the final visit. Subclassifying participants as those with minimal/moderate ischemia (16 participants, FAZ area <1,000 pixels) and those with more severe ischemia (14 participants, FAZ area >1,000 pixels) also showed no statistically significant change in the mean area of the FAZ. On average, BCVA increased and CST decreased from baseline to the final visit, but these changes were not statistically significant. Using per protocol analysis on those participants who completed the full course of treatment, the mean BCVA increased from 49.2 to 53.9 letters (P=0.046). Conclusion In this study, intravitreal injection of pegaptanib did not significantly alter the size of the FAZ in participants with varying degrees of ischemic DME. There was, however, a significant improvement in mean BCVA in those who completed the treatment course. PMID:26715833

  10. Risk of recurrence of retinopathy of prematurity after initial intravitreal ranibizumab therapy

    PubMed Central

    Chan, Joyce J. T.; Lam, Carol P. S.; Kwok, Madeline K. M.; Wong, Raymond L. M.; Lee, Gary K. Y.; Lau, Winnie W. Y.; Yam, Jason C. S.

    2016-01-01

    We report our experience with the use of intravitreal ranibizumab for the treatment of retinopathy of prematurity (ROP). A retrospective review was performed on 138 consecutive infants screened at a single centre over 18 months. Intravitreal ranibizumab was offered in selected cases requiring treatment, such as aggressive posterior ROP or poor mydriasis. 2 eyes of 1 infant received intravitreal ranibizumab alone and 8 eyes of 5 infants received combined intravitreal ranibizumab and laser therapy. 3 out of 8 eyes treated initially with intravitreal ranibizumab monotherapy had persistent disease requiring laser therapy, and 3 out of 5 eyes with initial regression suffered disease recurrence at a mean of 7.6 weeks post-injection. 2 eyes treated first with laser followed by intravitreal ranibizumab had disease regression without recurrence. Our cohort demonstrate a significant rate of persistent disease and recurrence in ROP eyes treated initially with intravitreal ranibizumab monotherapy, which is greater and earlier than that reported for intravitreal bevacizumab in the BEAT-ROP study. Intravitreal ranibizumab may be useful as an initial treatment in selected cases of ROP when laser therapy as first line is suboptimal. However, close monitoring is important and adjunctive laser therapy may subsequently be needed in a majority of cases. PMID:27256987

  11. Risk of recurrence of retinopathy of prematurity after initial intravitreal ranibizumab therapy.

    PubMed

    Chan, Joyce J T; Lam, Carol P S; Kwok, Madeline K M; Wong, Raymond L M; Lee, Gary K Y; Lau, Winnie W Y; Yam, Jason C S

    2016-01-01

    We report our experience with the use of intravitreal ranibizumab for the treatment of retinopathy of prematurity (ROP). A retrospective review was performed on 138 consecutive infants screened at a single centre over 18 months. Intravitreal ranibizumab was offered in selected cases requiring treatment, such as aggressive posterior ROP or poor mydriasis. 2 eyes of 1 infant received intravitreal ranibizumab alone and 8 eyes of 5 infants received combined intravitreal ranibizumab and laser therapy. 3 out of 8 eyes treated initially with intravitreal ranibizumab monotherapy had persistent disease requiring laser therapy, and 3 out of 5 eyes with initial regression suffered disease recurrence at a mean of 7.6 weeks post-injection. 2 eyes treated first with laser followed by intravitreal ranibizumab had disease regression without recurrence. Our cohort demonstrate a significant rate of persistent disease and recurrence in ROP eyes treated initially with intravitreal ranibizumab monotherapy, which is greater and earlier than that reported for intravitreal bevacizumab in the BEAT-ROP study. Intravitreal ranibizumab may be useful as an initial treatment in selected cases of ROP when laser therapy as first line is suboptimal. However, close monitoring is important and adjunctive laser therapy may subsequently be needed in a majority of cases. PMID:27256987

  12. Successful treatment of melanocytoma associated choroidal neovascular membrane with intravitreal bevacizumab.

    PubMed

    Al-Halafi, Ali M

    2013-04-01

    Melanocytoma of the optic disc is a benign melanocytic tumour that rarely causes visual impairment. We report a rare case of choroidal neovascularization (CNV) in association with optic disc melanocytoma and its response to intravitreal injection of the anti-vascular endothelial growth factor (VEGF), bevacizumab. The choroidal neovascular membrane regressed following a single intravitreal bevacizumab injection with formation of a scar. CNV associated with optic disc melanocytoma is rare. Intravitreal anti-VEGF treatment may be an effective treatment for CNV associated with optic disc melanocytoma. PMID:24227972

  13. Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion.

    PubMed

    Yang, Lily P H; McKeage, Kate

    2014-05-01

    Aflibercept is a fully human, recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF) family members, including VEGF-A, VEGF-B and placental growth factor (P1GF), thereby inhibiting downstream signalling mediated by these ligands. Aflibercept binds all isoforms of VEGF-A with high affinity, and a markedly higher affinity than that of ranibizumab or bevacizumab. A formulation of aflibercept developed specifically for intravitreal injection (Eylea(®)) is approved for use in several countries for the treatment of patients with macular oedema secondary to central retinal vein occlusion (CRVO). In clinical trials (GALILEO and COPERNICUS) in patients with this condition, intravitreal aflibercept 2 mg every month improved best corrected visual acuity (BCVA), as measured by the proportion of study eyes with a gain of ≥15 Early Treatment Diabetic Retinopathy Study letters from baseline, significantly more than sham injections at week 24 (primary analysis). The significant improvements achieved with intravitreal aflibercept compared with sham in the first 6 months were maintained in the second 6 months with as-needed (prn) dosing and monthly monitoring. Continued prn dosing with a reduced monitoring frequency was associated with decreased improvements. More data are needed to confirm the optimal monitoring frequency for use with prn dosing, subsequent to initial monthly injections, in order to maintain long-term efficacy. Intravitreal aflibercept was generally well tolerated in clinical trials and there is little potential for systemic drug accumulation. Thus, intravitreal aflibercept is an effective and generally well tolerated agent that extends the options available for the treatment of macular oedema secondary to CRVO. PMID:24740170

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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. PMID:24075925

  19. Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase III trials

    PubMed Central

    Danis, Ronald P; Sadda, Srinivas; Li, Xiao-Yan; Cui, Harry; Hashad, Yehia; Whitcup, Scott M

    2016-01-01

    Background/aim To assess long-term effects of dexamethasone intravitreal implant (DEX implant) monotherapy on retinal morphology in diabetic macular oedema (DME). Methods Two multicentre, masked, phase III studies with identical protocols randomised patients with DME, best-corrected visual acuity of 34–68 Early Treatment Diabetic Retinopathy Study letters and central subfield retinal thickness (CSRT) ≥300 µm to DEX implant 0.7, 0.35 mg or sham procedure. Patients were followed up for 3 years (39 months if treated at month 36), with retreatment allowed at ≥6-month intervals. Patients needing other macular oedema (ME) therapy exited the study. Changes from baseline in CSRT, macular volume and ME grade, area of retinal thickening, macular leakage, macular capillary loss and diabetic retinopathy severity were assessed. Results After 3 years, more eyes treated with DEX implant 0.7 and 0.35 mg than sham showed improvement (although small) in ME grade (p<0.05 vs sham). DEX implant 0.7 mg delayed time to onset of two-step progression in diabetic retinopathy severity by ∼12 months. DEX implant 0.7 and 0.35 mg produced small, non-sustained reductions in macular leakage but had no significant effect on macular capillary loss. Conclusions DEX implant 0.7 or 0.35 mg, administered at ≥6-month intervals over 3 years, produced sustained retinal structural improvement in DME. Trial registration number NCT00168337 and NCT00168389. PMID:26581718

  20. 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.

  1. Indications for Intravitreal Bevacizumab in Ibadan, Sub-Saharan Africa

    PubMed Central

    T.S, Oluleye; Y, Babalola

    2014-01-01

    Background : Angiogenesis is a contributing factor in some retinal diseases, hence the role of vascular endothelial growth factor (VEGF) as a common pathway in proliferative retinopathies. Bevacizumab has been found to be effective in the treatment of these diseases. The aim of this study was to review all cases of intravitreal bevacizumab given in the retinal unit of the University College Hospital, Ibadan from July, 2010 to June 2012, pointing out the common indications. Methods : After obtaining ethical approval from the University College Hospital/University of Ibadan Review Board for the study, all cases of intravitreal injections of bevacizumab recorded in the retinal register during the study period (July 2010 to June 2012) were retrieved. Age, sex, diagnoses and indication for injection were recorded in the data sheet prepared for the study. Results were analyzed using proportions and percentages. Results : A total of one hundred and thirty four injections of bevacizumab were given in the study period. The most common indication was cystoid macular edema from retinal vein occlusion ([26(19.4%)] followed by wet age related maculopathy [23(17.1%)] and sickle cell retinopathy [(22(16.4)]. Emerging indications included idiopathic polypoidal choroidal vasculopathy [8(6%) and retinal macroaneurism with macular edema [6(4.5%)]. Conclusion : Cystoid macular edema from vascular occlusion and wet age related macular degeneration are the major indications for intravitreal bevacizumab injection in Ibadan. PMID:25493104

  2. Analysis of Inadvertent Intradiscal Injections during Lumbar Transforaminal Epidural Injection

    PubMed Central

    Lee, Sung Mun; Bae, Jin Hong

    2014-01-01

    Background Recently, there have been several case reports and retrospective studies about the incidence of intradiscal (ID) injection during transforaminal epidural steroid injection (TFESI). Inadvertent ID injection is not a rare complication, and it carries the risk of developing diskitis, although there has been no report of diskitis after TFESI. We prospectively evaluated the incidence of inadvertent ID injection during lumbar TFESI and analyzed the contributing factors. Methods Ten patients received 2-level TFESI, and the remaining 229 patients received 1-level TFESI. When successful TFESI was performed, 2 ml of contrast dye was injected under real-time fluoroscopy to check for any inadvertent ID spread. A musculoskeletal radiologist analyzed all magnetic resonance images (MRIs) of patients who demonstrated inadvertent ID injection. When reviewing MRIs, the intervertebral foramen level where ID injection occurred was carefully examined, and any anatomical structure which narrowing the foramen was identified. Results Among the 249 TFESI, we identified 6 ID injections; thus, there was an incidence of 2.4%. Four patients had isthmic spondylolisthesis, and the level of spondylolisthesis coincided with the level of ID injection. We further examined the right or left foramen of the spondylolisthesis level and identified the upward migrated disc material that was narrowing the foramen. Conclusions Inadvertent ID injection during TFESI is not infrequent, and pain physicians must pay close attention to the type and location of disc herniation. PMID:24748946

  3. 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.

  4. 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

  5. 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

  6. Noise analysis of injection-locked semiconductor injection lasers

    SciTech Connect

    Schunk, N.; Peterman, K.

    1986-05-01

    The noise of injection-locked semiconductor lasers is analyzed by rate equations including the spontaneous emission noise. The side mode suppression and the relative intensity noise (RIN) of the locked laser (slave laser) are given for different wavelengths detuning between the master and slave laser and for different linewidth enhancement factors ..cap alpha... For large ..cap alpha.., locking is difficult to achieve, whereas extremely low noise may be obtained for injection-locked lasers with a low linewidth enhancement factor.

  7. Ceramic injection molding material analysis, modeling and injection molding simulation

    NASA Astrophysics Data System (ADS)

    Drummer, D.; Messingschlager, S.

    2014-05-01

    In comparison to unfilled polymers, a ceramic feedstocks has a very high viscosity, a very high heat conductivity and a different pvT-behavior. So far standard simulation tools for plastic injection molding are capable of simulating unfilled or fiber filled compounds with their typical low viscosity and heat conductivity etc. but not for very high ceramic powder filled polymers. This article shows an approach of preparing and adding ceramic feedstocks to standard injection molding tools. Two different feedstocks are used.

  8. 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

  9. 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.

  10. Intravitreal Steroids for the Treatment of Retinal Diseases

    PubMed Central

    Veritti, Daniele; Boscia, Francesco

    2014-01-01

    Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events. PMID:24526927

  11. Intravitreal steroids for the treatment of retinal diseases.

    PubMed

    Sarao, Valentina; Veritti, Daniele; Boscia, Francesco; Lanzetta, Paolo

    2014-01-01

    Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events. PMID:24526927

  12. The Effect of Intravitreal Azithromycin on the Albino Newborn Rabbit Retina

    PubMed Central

    Cam, Duygu; Saatci, Ali Osman; Micili, Serap Cilaker; Ergur, Bekir Ugur; Karabag, Revan Yildirim; Durak, Ismet; Berk, Ayse Tulin

    2016-01-01

    Purpose: To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model. Methods: Twelve, two-week old New Zealand albino rabbits were divided into two groups (six in each). The right eyes of six rabbits received 0.75 mg (0.05 mL) azithromycin and the right eyes of the remaining six rabbits 1.5 mg (0.1 mL) azithromycin intravitreally. Left eyes were served as the control and received the same volume of saline. All eyes were enucleated at the third postinjection week. Retinal histology was examined by light microscopy. Apoptosis of the retinal cells was further evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments. Results: Light microscopy demonstrated no retinal abnormalities in all eyes. However, retinal nuclear DNA fragmentation was evident in both study groups (33.6% with 1.5 mg and 21.4% with 0.75 mg azithromycin) with the TUNEL method. TUNEL staining ratio was statistically higher only in the second group treated with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratio of caspase-3 positive cells in the two study groups was 21.5% and 20.2%, respectively. Caspase-3 staining ratio was statistically higher in both study groups when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two study groups was statistically significant (p=0.028), but there were no statistically significant differences in the two study groups by caspase-3 staining (p=0.247). Conclusion: In newborn rabbits, intravitreal azithromycin injection resulted in an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Immunohistochemical analysis suggested that doses of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the newborn rabbit retina. PMID:27014381

  13. Tyrosine capsid-mutant AAV vectors for gene delivery to the canine retina from a subretinal or intravitreal approach

    PubMed Central

    Mowat, FM; Gornik, KR; Dinculescu, A; Boye, SL; Hauswirth, WW; Petersen-Jones, SM; Bartoe, JT

    2013-01-01

    Recombinant adeno-associated viruses are important vectors for retinal gene delivery. Currently utilized vectors have relatively slow onset and for efficient transduction it is necessary to deliver treatment subretinally, with the potential for damage to the retina. Amino-acid substitutions in the viral capsid improve efficiency in rodent eyes by evading host responses. As dogs are important large animal models for human retinitis pigmentosa, we evaluated the speed and efficiency of retinal transduction using capsid-mutant vectors injected both subretinally and intravitreally. We evaluated AAV serotypes 2 and 8 with amino-acid substitutions of surface exposed capsid tyrosine residues. The chicken beta-actin promoter was used to drive green fluorescent protein expression. Twelve normal adult beagles were injected, 4 dogs received intravitreal injections, 8 dogs received subretinal injections. Capsid-mutant viruses tested included AAV2(quad Y-F) (intravitreal and subretinal), and self-complementary scAAV8(Y733F) (subretinal only). Contralateral control eyes received injections of scAAV5 (subretinal) or scAAV2 (intravitreal). Subretinally delivered vectors had a faster expression onset than intravitreally delivered vectors. Subretinally delivered scAAV8(Y733F) had a faster onset of expression than scAAV5. All subretinally injected vector types transduced the outer retina with high efficiency, and the inner retina with moderate efficiency. Intravitreally delivered AAV2(quad Y-F) had a marginally higher efficiency of transduction of both outer retinal and inner retinal cells than scAAV2. Because of their rapid expression onset and efficient transduction, subretinally delivered capsid-mutant AAV8 vectors may increase the efficacy of gene therapy treatment for rapid photoreceptor degenerative diseases. With further refinement, capsid-mutant AAV2 vectors show promise for retinal gene delivery from an intravitreal approach. PMID:24225638

  14. 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

  15. Selective Gene Transfer to the Retina Using Intravitreal Ultrasound Irradiation

    PubMed Central

    Sonoda, Shozo; Tachibana, Katsuro; Yamashita, Toshifumi; Shirasawa, Makoto; Terasaki, Hiroto; Uchino, Eisuke; Suzuki, Ryo; Maruyama, Kazuo; Sakamoto, Taiji

    2012-01-01

    This paper aims to evaluate the efficacy of intravitreal ultrasound (US) irradiation for green fluorescent protein (GFP) plasmid transfer into the rabbit retina using a miniature US transducer. Intravitreal US irradiation was performed by a slight modification of the transconjunctival sutureless vitrectomy system utilizing a small probe. After vitrectomy, the US probe was inserted through a scleral incision. A mixture of GFP plasmid (50 μL) and bubble liposomes (BLs; 50 μL) was injected into the vitreous cavity, and US was generated to the retina using a SonoPore 4000. The control group was not exposed to US. After 72 h, the gene-transfer efficiency was quantified by counting the number of GFP-positive cells. The retinas that received plasmid, BL, and US showed a significant increase in the number (average ± SEM) of GFP-positive cells (32 ± 4.9; n = 7; P < 0.01 ). No GFP-positive cells were observed in the control eyes (n = 7). Intravitreal retinal US irradiation can transfer the GFP plasmid into the retina without causing any apparent damage. This procedure could be used to transfer genes and drugs directly to the retina and therefore has potential therapeutic value. PMID:22518277

  16. Recent advances in flow injection analysis.

    PubMed

    Trojanowicz, Marek; Kołacińska, Kamila

    2016-04-01

    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. PMID:26906258

  17. Combination of intravitreal bevacizumab and peripheral photocoagulation: an alternative treatment in eales disease.

    PubMed

    Cp, Juarez; Al, Gramajo; Jd, Luna

    2013-01-01

    To report the efficacy of combination therapy (bevacizumab and photocoagulation) in a case of Eales Disease this study has been performed. Bevacizumab (Avastin, 1.25 mg/0.05 ml) was injected intravitreously for the treatment of iris and retinal neovascularization in a 56-year old Hispanic female with photocoagulation treatment to control the recurrence of vitreous haemorrhage. Our results revealed that stabilization of the disease and improvement in visual acuity were achieved without any signs of recurrence. Intravitreal bevacizumab in combination with photocoagulation treatment of ischemic retinal areas may be a good alternative for patients with recurrent vitreous haemorrhage due to Eales disease. PMID:24600639

  18. Combination of Intravitreal Bevacizumab and Peripheral Photocoagulation: An Alternative Treatment in Eales Disease

    PubMed Central

    CP, Juarez; AL, Gramajo; JD, Luna

    2013-01-01

    To report the efficacy of combination therapy (bevacizumab and photocoagulation) in a case of Eales Disease this study has been performed. Bevacizumab (Avastin, 1.25 mg/0.05 ml) was injected intravitreously for the treatment of iris and retinal neovascularization in a 56-year old Hispanic female with photocoagulation treatment to control the recurrence of vitreous haemorrhage. Our results revealed that stabilization of the disease and improvement in visual acuity were achieved without any signs of recurrence. Intravitreal bevacizumab in combination with photocoagulation treatment of ischemic retinal areas may be a good alternative for patients with recurrent vitreous haemorrhage due to Eales disease. PMID:24600639

  19. Fusarium Endophthalmitis following Cataract Surgery: Successful Treatment with Intravitreal and Systemic Voriconazole

    PubMed Central

    Logroño, Juan F. Batlle

    2016-01-01

    Purpose. To report a case of postoperative endophthalmitis caused by Fusarium species successfully treated with intravitreal and systemic voriconazole after treatment failure with amphotericin B. Methods. Clinical case report of a 60-year-old immunocompetent woman who presents with endophthalmitis of unknown origin 4 weeks after uneventful cataract extraction and IOL implantation surgery. IOL explantation, vitrectomy with capsular bag removal, vitreous aspiration for culture, and intravitreal injection of amphotericin B (5 μg/0.1 mL) were performed. Diagnosis was established by culturing the vitreous aspirate on a Sabouraud agar medium and staining with lactophenol blue solution. Five days later, there was no clinical response. The decision was made to administer a single dose of intravitreal voriconazole (2.5 μg/0.1 mL) and oral voriconazole (200 mg BID) for 30 days. Results. Fusarium sp. grew on culture. Treatment with local and systemic voriconazole was started after no improvement with vitrectomy, IOL explantation, and intravitreal amphotericin B. After 1 month of treatment, the infection resolved and best-corrected visual acuity was 20/25. Conclusion. In patients with endophthalmitis caused by Fusarium sp., topical and systemic voriconazole treatment should be considered in cases resistant to intravitreal amphotericin B. PMID:27418989

  20. Ocular Pulse Amplitude and Retinal Vessel Caliber Changes after Intravitreal Dexamethasone Implant

    PubMed Central

    Yilmaz, Ihsan; Perente, Irfan; Kesim, Cem; Saracoglu, Basak; Yazici, Ahmet Taylan; Taskapili, Muhittin

    2016-01-01

    Purpose: The purpose of this study is to evaluate possible changes in ocular pulse amplitude (OPA), retinal arteriole caliber (RAC), and retinal venule caliber (RVC), following the intravitreal injection of dexamethasone implants (DIs). Methods: Thirty-four eyes of 34 patients with macular edema were included. All participants received a full ophthalmologic examination at baseline. RAC and RVC were measured via optical coherence tomography; OPA and intraocular pressure (IOP) were measured via dynamic contour tonometry at baseline, month 1, and month 3. Statistical analysis was performed for before-after comparison of OPA, IOP, RAC, and RVC measurements. Results: The mean OPA (in order to baseline, month 1, month 3) was 2.8 ± 0.8, 2.9 ± 1.0, 2.9 ± 0.9. The mean IOP was 16.8 ± 2.9, 17.3 ± 2.7, 18.4 ± 2.9 mmHg. The mean RAC was 97.8 ± 9.2, 97.2 ± 9.0, 97.6 ± 9.4. The mean RVC was 124.4 ± 8.2, 124.8 ± 8.8, 123.8 ± 8.2. There were no statistically significant changes in RAC (P = 0.688), RVC (P = 0.714), OPA (P = 0.348), and IOP (P = 0.115). There was also no correlation between RAC and OPA (r = 0.12, P = 0.62) or RVC and OPA (r = 0.16, P = 0.68) at the last visit. Conclusion: The intravitreal injection of DI does not significantly affect RAC, RVC, or OPA, which indicates that the treatment does not alter overall retinal-choroidal vasculature or hemodynamics.

  1. Intravitreal bevacizumab in the treatment of vasoproliferative retinal tumours

    PubMed Central

    Rogers, C; Damato, B; Kumar, I; Heimann, H

    2014-01-01

    Aim To evaluate the efficacy of intravitreal bevacizumab in the treatment of retinal vasoproliferative tumours (VPT). Materials and Methods Six eyes of 6 patients with VPT who received intravitreal bevacizumab were retrospectively reviewed. All patients received between one and three injections of intravitreal bevacizumab depending upon response to treatment. Best-corrected visual acuity (BCVA), tumour size, and presence of co-pathology or sequelae were noted pre- and postoperatively and then analysed. Subsequent retreatments were performed in patients with recurrent or persistent VPT according to the ophthalmologist's discretion. Retreatments included photodynamic therapy with verteporfin, ruthenium-106 plaque brachytherapy, or endoresection of tumour. Results The mean follow-up duration was 33.3 months (range 10–66 months). At baseline, the mean logMAR BCVA was 1.45 (Snellen equivalent of 6/165); range 0.10–1.90 (6/8—CF). Following bevacizumab treatment the mean logMAR BCVA was 0.98 (Snellen equivalent of 6/57); range 0.5–1.9 (Snellen equivalent of 6/19 to CF). Therefore, there was no statistically significant change in visual acuity. The mean tumour thickness reduced from 2.4 to 2.1 mm following treatment with bevacizumab. However, this did not reach the statistical significance of P<0.05. Despite the visual improvement following bevacizumab therapy, five out of six patients had recurrence of tumour activity during the follow-up period and required further intervention in order to achieve sustained regression. Conclusions Intravitreal bevacizumab appeared to result in temporary reduction of tumour thickness in 3 out of 6 VPT patients. However, neither the reduction in tumour thickness nor the change in visual acuity were statistically significant and intravitreal bevacizumab monotherapy had limited effectiveness in causing long-term regression of the lesions. Additional therapy was indicated in five out of six patients to establish long-term regression

  2. Evaluation of the effectiveness and safety of glucocorticoids intravitreal implant therapy in macular edema due to retinal vein occlusion

    PubMed Central

    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. PMID

  3. Intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks: A report of two patients

    PubMed Central

    Ozkaya, Abdullah; Alkin, Zeynep; Faiz, Miray; Yazici, Ahmet Taylan; Demirok, Ahmet

    2013-01-01

    The aim of this study is to report clinical course of choroidal neovascularization secondary to angioid streaks (AS) in two patients who underwent intravitreal bevacizumab therapy. Fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT) revealed the diagnosis of subfoveal classic choroidal neovascularization (CNV) in the right eye in patient 1 and in the left eye in patient 2. After three consecutive bevacizumab injections, visual acuity improved from 20/40 to 20/25 in patient 1 and from 20/80 to 20/50 in patient 2. After 3 months of therapy, additional bevacizumab injection was administered when the lesion showed recurrence. After a follow-up time of 24-months, patient 1 received 14 intravitreal bevacizumab injections; patient 2 received only 4 injections. Visual acuities remained stable at 20/32 and 20/50 in patient 1 and patient 2, respectively. Though, the patients of CNV secondary to AS showed similar clinical appearance at the beginning, this report provides the data for different responses to intravitreal bevacizumab therapy. While fewer injections were required to control the disease in one patient, the other patient needed much more injections for stabilization of the CNV. Further studies are required to understand the cause of varied treatment responses in those patients. PMID:25473350

  4. Multiple-injection high-throughput gas chromatography analysis.

    PubMed

    Schafer, Wes; Wang, Heather; Welch, Christopher J

    2016-08-01

    Multiple-injection techniques have been shown to be a simple way to perform high-throughput analysis where the entire experiment resides in a single chromatogram, simplifying the data analysis and interpretation. In this study, multiple-injection techniques are applied to gas chromatography with flame ionization detection and mass detection to significantly increase sample throughput. The unique issues of implementing a traditional "Fast" injection mode of multiple-injection techniques with gas chromatography and mass spectrometry are discussed. Stacked injections are also discussed as means to increase the throughput of longer methods where mass detection is unable to distinguish between analytes of the same mass and longer retentions are required to resolve components of interest. Multiple-injection techniques are shown to increase instrument throughput by up to 70% and to simplify data analysis, allowing hits in multiple parallel experiments to be identified easily. PMID:27292909

  5. Intravitreal bevacizumab monotherapy for choroidal neovascularisation secondary to choroidal osteoma.

    PubMed

    Papastefanou, V P; Pefkianaki, M; Al Harby, L; Arora, A K; Cohen, V M L; Andrews, R M; Sagoo, M S

    2016-06-01

    PurposeThe purpose of this study is to present the outcomes of a series of patients with choroidal neovascular membrane (choroidal neovascularisation (CNV)) secondary to a choroidal osteoma undergoing anti-VEGF monotherapy.Patients and methodsRetrospective series of patients with choroidal neovascularization secondary to choroidal osteoma. All patients underwent clinical and imaging assessment (fundus photo, B-scan ultrasonography, fluorescein angiography, and optical coherence tomography-where available), and were managed with intravitreal anti-VEGF injections (Bevacizumab). Visual acuity and central retinal thickness were recorded pre treatment and at the end of the follow-up period.ResultsEight patients were included in this study. Of this, 6/8 had predominantly classic or classic and 2/8 patients had minimally classic or occult CNV. Each patient received 3-10 injections of bevacizumab. Median follow-up was 9 months (3-15 months). Visual acuity improved in 5 patients, by 2-6 Snellen lines. CNV completely regressed in 5 cases and partially regressed in 3 cases. Mean CRT reduction was 122 μm (6 to -230 μm).ConclusionIntravitreal bevacizumab can be an effective treatment modality in the management of vision threatening CNV secondary to choroidal osteoma. PMID:27034203

  6. Intraocular Pressure Changes in Non-Glaucomatous Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Agents

    PubMed Central

    Kiddee, Weerawat; Montriwet, Mayuree

    2015-01-01

    Purpose To study the prevalence of sustained intraocular pressure (IOP) elevation associated with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. Methods Prospective comparative study. Non-glaucomatous patients scheduled to receive intravitreal injection of anti-VEGF therapy were recruited from an outpatient eye clinic, Songklanagarind Hospital between April 2013 and March 2014. The IOP was measured by Goldmann applanation tonometer before and at 1 hour, 1 week, 1 month, 3 months, and 6 months after injection. The IOP was compared using the repeated measures analysis. Sustained IOP elevation was defined as either an IOP > 21 mmHg or an increase from baseline ≥ 5 mmHg on two consecutive visits. Results Seventy eyes of 54 patients met the inclusion criteria. The most common diagnosis was diabetic macular edema (48%). The mean IOP ± standard deviation (SD) before treatment was 13.7 ± 2.8 mmHg. The means ± SDs after treatment at 1 hour, 1 week, 1 month, 3 months, and 6 months were 11.3 ± 2.6, 13.7 ± 3.6, 14.1 ± 3.3, 14.0 ± 2.3, and 13.7 ± 2.4 mmHg, respectively. A mean of IOP difference at 1 hour postinjection and at baseline was −2.36 ± 2.5 mmHg (P < 0.001). Four of 70 treated eyes (5.7%) developed sustained IOP elevation (IOP ≥ 5 mmHg from baseline on two consecutive visits). The IOP returned to baseline levels after 1 month, in three eyes. One eye had sustained IOP elevation at 3 and 6 months follow-up. Thereafter, IOP returned to baseline level. There was no need of anti-glaucoma medication. Conclusions After receiving intravitreal injection of anti-VEGF agent, a small proportion of non-glaucomatous eyes developed a sustained IOP elevation without requiring IOP-lowering treatment. At 1 hour postinjection, there was a significant reduction of the mean IOP compared with the baseline level. PMID:26360382

  7. 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

  8. Feline ocular tumors following ciliary body ablation with intravitreal gentamicin.

    PubMed

    Duke, Felicia D; Strong, Travis D; Bentley, Ellison; Dubielzig, Richard R

    2013-07-01

    Practitioners approach chemical ciliary body ablation (CBA) in cats with caution. In 1994, an academic letter proposed a potential link between intraocular gentamicin injections for glaucoma and the appearance of ocular tumors in cats (Veterinary and Comparative Ophthalmology, 4, 1994, 166). There is an historic perceived risk for the development of feline ocular post-traumatic sarcoma following gentamicin ciliary body ablation, and many clinicians refrain from chemical ablation in cats for this reason. A recent study discussed the possibility of a correlation between intravitreal gentamicin and tumor promotion in dogs (Veterinary Ophthalmology, 16, 2013, 159). We searched the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database for cases of cats diagnosed with ocular tumors following ciliary body ablation. Of eight cases with historic gentamicin injection, five had malignant tumors: three post-traumatic sarcomas and two melanomas. PMID:23701585

  9. Pharmacokinetics of intravitreal antibiotics in endophthalmitis

    PubMed Central

    2014-01-01

    Intravitreal antibiotics are the mainstay of treatment in the management of infectious endophthalmitis. Basic knowledge of the commonly used intravitreal antibiotics, which includes their pharmacokinetics, half-life, duration of action and clearance, is essential for elimination of intraocular infection without any iatrogenic adverse effect to the ocular tissue. Various drugs have been studied over the past century to achieve this goal. We performed a comprehensive review of the antibiotics which have been used for intravitreal route and the pharmacokinetic factors influencing the drug delivery and safety profile of these antibiotics. Using online resources like PubMed and Google Scholar, articles were reviewed. The articles were confined to the English language only. We present a broad overview of pharmacokinetic concepts fundamental for use of intravitreal antibiotics in endophthalmitis along with a tabulated compendium of the intravitreal antibiotics using available literature. Recent advances for increasing bioavailability of antibiotics to the posterior segment with the development of controlled drug delivery devices are also described. PMID:25667683

  10. 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

  11. 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.

  12. Micelle formulation of Hexadecyloxypropyl-Cidofovir (HDP-CDV) as an intravitreal long-lasting delivery system

    PubMed Central

    Ma, Feiyan; Nan, Kaihui; Lee, SuNa; Beadle, James R.; Hou, Huiyuan; Freeman, William R.; Hostetler, Karl Y.; Cheng, Lingyun

    2014-01-01

    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. PMID:25513956

  13. 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.

  14. 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. PMID:26416040

  15. Intravitreal clearance and volume of distribution of compounds in rabbits: In silico prediction and pharmacokinetic simulations for drug development.

    PubMed

    del Amo, Eva M; Vellonen, Kati-Sisko; Kidron, Heidi; Urtti, Arto

    2015-09-01

    The aims of this research were to (1) create a curated universal database of intravitreal volumes of distribution (Vss, ivt) and clearances (CL ivt) of small molecular weight compounds and macromolecules and (2) to develop quantitative structure property relationship (QSPR) and pharmacokinetic models for the estimation of vitreal drug concentrations based on the compound structure. Vss, ivt and CL ivt values were determined from the available literature on intravitreal drug administration using compartmental models and curve fitting. A simple QSPR model for CL ivt of small molecular weight compounds was obtained with two descriptors: Log D7.4 and hydrogen bond donor capacity. The model predicted the internal and external test sets reliably with a mean fold error of 1.50 and 1.33, respectively (Q(2)Y=0.62). For 80% of the compounds the Vss, ivt was 1.18-2.28 ml; too narrow range for QSPR model building. Integration of the estimated Vss, ivt and predicted CL ivt parameters into pharmacokinetic simulation models allows prediction of vitreous drug concentrations after intravitreal administration. The present work presents for the first time a database of CL ivt and Vss, ivt values and the dependence of the CL ivt values on the molecular structure. The study provides also useful in silico tools to investigate a priori the intravitreal pharmacokinetic profiles for intravitreally injected candidate compounds and drug delivery systems. PMID:25603198

  16. 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

  17. Comparative role of intravitreal ranibizumab versus bevacizumab in choroidal neovascular membrane in age-related macular degeneration

    PubMed Central

    Biswas, Partha; Sengupta, Subhrangshu; Choudhary, Ruby; Home, Subhankar; Paul, Ajoy; Sinha, Sourav

    2011-01-01

    Context: Ranibizumab and bevacizumab are used widely for treating patients with choroidal neovascular membrane (CNVM) secondary to age-related macular degeneration (AMD). Aims: To determine and compare the efficacy and safety of intravitreal ranibizumab and bevacizumab in treatment of CNVM due to AMD. Settings and Design: Prospective comparative case series carried out in an eye institute and eye department of a hospital in Kolkata, India. Materials and Methods: One hundred and four eyes with CNVM due to AMD were randomized into two groups. Group A (n=54; 24 occult) received monthly intravitreal ranibizumab injections (0.5 mg in 0.05 ml) and Group B (n=50; 22 occult) received monthly bevacizumab injections (1.25 mg in 0.05 ml) for 3 consecutive months and then as per study criteria. Data analysis done using SPSS software. P-value of <0.05 was considered statistically significant. Results: The mean best corrected visual acuity (BCVA) in the ranibizumab group increased from 58.19 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 64 ETDRS letters at month 3 (P<0.001). In bevacizumab group mean BCVA increased from 56.80 to 61.72 ETDRS letters at month 3 (P<0.001). At the end of 18 months, there was no statistically significant difference between groups A and B with respect to change in BCVA (P=0.563) or central macular thickness (CMT; P=0.281), as measured by optical coherence tomography (Stratus OCT 3000). No significant sight-threatening complications developed. Conclusions: Ranibizumab and bevacizumab are equally safe and efficacious in treating CNVM due to AMD. PMID:21586838

  18. Canine ocular tumors following ciliary body ablation with intravitreal gentamicin.

    PubMed

    Duke, Felicia D; Strong, Travis D; Bentley, Ellison; Dubielzig, Richard R

    2013-03-01

    Iridociliary tumors are the second most common primary ocular tumor in dogs and are usually benign. A review of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database in 2009 suggested a potential correlation between malignant iridociliary epithelial tumors and ciliary body ablation by intravitreal gentamicin injection for the treatment of glaucoma. The purpose of this case series was to determine whether there is evidence of such a correlation in the COPLOW collection. Mining of the COPLOW database revealed that a significant number (39.5%) of canine globes with a history of ciliary body ablation were subsequently diagnosed with primary ocular tumors at enucleation, most commonly iridociliary epithelial tumors and melanocytic tumors. It is possible that neoplasia was present but unrecognized at the time of ciliary body ablation. These tumors had a higher than expected incidence of malignancy. These cases underscore the importance of reserving ciliary body ablation with gentamicin for disease-free eyes. PMID:22812389

  19. ANATOMIC AND PHARMACOKINETIC PROPERTIES OF INTRAVITREAL BEVACIZUMAB AND RANIBIZUMAB AFTER VITRECTOMY AND LENSECTOMY

    PubMed Central

    CHRISTOFORIDIS, JOHN B.; CARLTON, MICHELLE M.; WANG, JILLIAN; JIANG, ANGELA; PRATT, CEDRIC; ABDEL-RASOUL, MAHMOUD; HINKLE, GEORGE H.; KNOPP, MICHAEL V.

    2014-01-01

    Purpose To determine the anatomic characteristics and pharmacokinetic properties of intravitreally placed bevacizumab and ranibizumab after pars plana lensectomy or pars plana vitrectomy and to compare these with nonoperated control eyes in a rabbit model. Methods Three groups of six Dutch-belted rabbits each underwent pars plana vitrectomy, pars plana lensectomy, or served as nonsurgical controls. Twelve days after surgery, 3 rabbits from each group underwent intravitreal injection in one eye with 1.25 mg/0.05 mL I-124–bevacizumab or 0.5 mg/0.05 mL I-124-ranibizumab. Serial imaging with PET/CT were obtained on Days 0, 2, 5, 7, 14, 21, 28, and 35. Measured radioactivity emission in becquerels/milliliter was used to calculate the half-lives for each agent. Results The intravitreally placed radiolabeled agents were contained within the vitreous cavity for the duration of the study. The average clearance half-lives with standard error for bevacizumab and ranibizumab after correction for radioactive decay were, respectively, 4.22 ± 0.07 days and 2.81 ± 0.05 days in unoperated eyes, 2.30 ± 0.09 days (P < 0.0001) and 2.13 ± 0.05 days (P < 0.0001) after vitrectomy, and 2.08 ± 0.07 days (P = 0.0001) and 1.79 ± 0.05 days (P < 0.0001) after lensectomy. Conclusion Intravitreal retention was longer for bevacizumab than ranibizumab within all study groups and was significantly reduced after vitrectomy and lensectomy for both agents. Consideration for more frequent intravitreal anti–vascular endothelial growth factor dosing regimens may be made for patients whose treated eyes have undergone previous vitrectomy or who are aphakic. PMID:23407351

  20. Resolution of Persistent Cystoid Macular Edema due to Central Retinal Vein Occlusion in a Vitrectomized Eye following Intravitreal Implant of Dexamethasone 0.7 mg

    PubMed Central

    Reibaldi, Michele; Russo, Andrea; Zagari, Marco; Toro, Mario; Grande De, Vittorio; Cifalinò, Valentina; Rametta, Stefania; Faro, Salvatore; Longo, Antonio

    2012-01-01

    We report the case of a 62-year-old woman with a history of vitreoretinal surgery for vitreous hemorrhage secondary to central retinal vein occlusion (CRVO). Because of the persistence of macular edema (ME), she received 2 intravitreal injections of bevacizumab 0.5 mg (Avastin®, Genentech/Roche) three months after vitrectomy, without functional or anatomical improvement. Six months after vitrectomy, she therefore received an intravitreal implant of dexamethasone 0.7 mg (Ozurdex®). An improvement in her best-corrected visual acuity and central macular thickness, as measured by optical coherence tomography, was detected 7 days after the injection, and complete resolution of the ME and retinal hemorrhages was observed 6 months after the injection. Dexamethasone intravitreal implant might be an effective treatment option in ME secondary to CRVO, also in vitrectomized eyes. PMID:22615698

  1. Comparison of dexamethasone intravitreal implant and intravitreal triamcinolone acetonide for the treatment of pseudophakic cystoid macular edema in diabetic patients

    PubMed Central

    Dang, Yalong; Mu, Yalin; Li, Lin; Mu, Yahui; Liu, Shujing; Zhang, Chun; Zhu, Yu; Xu, Yimin

    2014-01-01

    ). Conclusion Both IVTA and DEX implants could effectively restore visual function and recover morphological change in diabetic patients with PCME for at least 6 months, but repeated intravitreal injection was required in the IVTA group. DEX implant is well tolerated. We suggest that intravitreal injection of DEX implant is a promising new therapeutic option for diabetic patients with PCME. PMID:25258512

  2. 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

  3. 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

  4. Analysis of PWR RCS Injection Strategy During Severe Accident

    SciTech Connect

    Wang, S.-J.; Chiang, K.-S.; Chiang, S.-C.

    2004-05-15

    Reactor coolant system (RCS) injection is an important strategy for severe accident management of a pressurized water reactor (PWR) system. Maanshan is a typical Westinghouse PWR nuclear power plant (NPP) with large, dry containment. The severe accident management guideline (SAMG) of Maanshan NPP is developed based on the Westinghouse Owners Group (WOG) SAMG.The purpose of this work is to analyze the RCS injection strategy of PWR system in an overheated core condition. Power is assumed recovered as the vessel water level drops to the bottom of active fuel. The Modular Accident Analysis Program version 4.0.4 (MAAP4) code is chosen as a tool for analysis. A postulated station blackout sequence for Maanshan NPP is cited as a reference case for this analysis. The hot leg creep rupture occurs during the mitigation action with immediate injection after power recovery according to WOG SAMG, which is not desired. This phenomenon is not considered while developing the WOG SAMG. Two other RCS injection methods are analyzed by using MAAP4. The RCS injection strategy is modified in the Maanshan SAMG. These results can be applied for typical PWR NPPs.

  5. Successful Management of Diffuse Unilateral Subacute Neuroretinitis with Anthelmintics, and Intravitreal Triamcinolone followed by Laser Photocoagulation

    PubMed Central

    Lima, Behzad Safarpour; Ramezani, Alireza; Soheilian, Masoud; Rastegarpour, Ali; Roshandel, Danial; Sayanjali, Shima

    2016-01-01

    Purpose: Diffuse unilateral subacute neuroretinitis (DUSN), a form of posterior uveitis, is secondary to the presence of a highly motile nematode in the intraretinal or subretinal space. Herein, we report a case of DUSN that was successfully managed by an intravitreal injection of triamcinolone and laser therapy. Case Report: A middle-aged man with complaint of decreased vision and marked unilateral vitritis and neuroretinitis. Fluorescein angiography revealed disc leakage, vessel wall staining, and diffuse track-like transmission defects of the RPE. Optical coherence tomography confirmed the subretinal location of the worm. The patient received oral thiabendazole and an intravitreal injection of triamcinolone acetonide. After 10 days, media haziness decreased, and a live motile subretinal worm was identified. Direct laser photocoagulation was performed to destroy the worm. After two months, a localized chorioretinal scar developed and no further active inflammation and subretinal worms were detected. Conclusion: Intravitreal steroids can be used safely in cases with DUSN and may help detect the causative worm for applying laser photocoagulation. PMID:27195096

  6. 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

  7. Analysis of injection tests in liquid-dominated geothermal reservoirs

    SciTech Connect

    Benson, S.M.

    1984-12-01

    The objective was to develop procedures for analyzing nonisothermal injection test data during the early phases of injection. In particular, methods for determining the permeability-thickness of the formation, skin factor of the well and tracking the movement of the thermal front have been developed. The techniques developed for interpreting injection pressure transients are closely akin to conventional groundwater and petroleum techniques for evaluating these parameters. The approach taken was to numerically simulate injection with a variety of temperatures, reservoir parameters and flowrates, in order to determine the characteristic responses due to nonisothermal injection. Two characteristic responses were identified: moving front dominated behavior and composite reservoir behavior. Analysis procedures for calculating the permeability-thickness of the formation and the skin factor of the well have been developed for each of these cases. In order to interpret the composite reservior behavior, a new concept has been developed; that of a ''fluid skin factor'', which accounts for the steady-state pressure buildup due to the region inside the thermal front. Based on this same concept, a procedure for tracking the movement of the thermal front has been established. The results also identify the dangers of not accounting the nonisothermal effects when analyzing injection test data. Both the permeability-thickness and skin factor of the well can be grossly miscalculated if the effects of the cold-region around the well are not taken into consideration. 47 refs., 30 figs., 14 tabs.

  8. Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy

    PubMed Central

    Brito, Isis A. S.; Zacharias, Leandro C.; Pimentel, Sérgio Luis G.

    2015-01-01

    Radiation retinopathy (RR) is a progressive, chronic condition directly related to the amount of radiation administered to the retina. We report a 37-year-old patient with medulloblastoma that was treated with external beam radiation and presented to us with bilateral cystoid macular edema. He was treated with monthly bevacizumab injections only in his worst seeing eye. There was a significant improvement in his fellow eye, with marked retinal thickness reduction. Therefore, we present clinical evidence of systemic absorption and fellow eye activity of the drug (bevacizumab). One must be aware of distant side effects after intravitreal injections. PMID:26635985

  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. 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)

  11. Thermostructural analysis of a scramjet fuel-injection strut

    NASA Technical Reports Server (NTRS)

    Wieting, A. R.; Thornton, E. A.

    1978-01-01

    Results of a thermal/structural design analysis study of a fuel injection strut for an airframe integrated hydrogen cooled scramjet are presented. It is indicated that a feasible thermal/structural concept has been identified for the static load conditions and that thermal stresses dominate the response. It is suggested that the response of the concept to dynamic loads be investigated.

  12. Failure of intravitreal bevacizumab in the treatment of choroidal metastasis

    PubMed Central

    Maudgil, A; Sears, K S; Rundle, P A; Rennie, I G; Salvi, S M

    2015-01-01

    Background Metastasis to choroid is the most common intraocular malignancy, arising most frequently from carcinoma of breast in women and lung in men. Recent case reports have described successful use of intravitreal bevacizumab to achieve local control of such tumours. Materials and methods Five cases of choroidal metastases from varying primaries: breast, lung, and colon were treated with intravitreal bevacizumab, and tumour response observed and documented with serial photographs and B-scans. Results Four of the five tumours were seen to progress despite intravitreal bevacizumab treatment. Conclusions Intravitreal bevacizumab as the primary treatment of choroidal metastases is not recommended and should not delay more effective alternative treatments. PMID:25771814

  13. A Homemade Autosampler/Injector Commutator for Flow Injection Analysis

    PubMed Central

    de Figueiredo, Eduardo Costa; de Souza, Leandro Ruela; de Magalhães, Cristiana Schmidt; Wisniewski, Célio

    2006-01-01

    An autosampler/injector commutator for flow injection analysis (FIA) was constructed with electronic components of used equipments. The apparatus is controlled by commercially available multifunctional interface (PCL711B) connected to a personal computer, and the software was written in Visual Basic language. The system was applied to water analysis and it presented satisfactory results. The low cost and simplicity are the principal characteristics of the autosampler/injector commutator. PMID:17671617

  14. High dose intravitreal foscarnet in the treatment of cytomegalovirus retinitis in AIDS.

    PubMed Central

    Diaz-Llopis, M; España, E; Muñoz, G; Navea, A; Chipont, E; Cano, J; Menezo, J L; Romero, F J

    1994-01-01

    The efficacy and tolerance of high dose intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS was studied. Foscarnet in a dose of 2400 micrograms was injected directly into the vitreous of 11 patients (15 eyes). Five patients had active retinitis (eight eyes, 53.3%), and received a 3 week induction therapy of six injections as the first step. Six patients had initial inactive retinitis (seven eyes, 46.7%), and received only maintenance therapy which consisted of a weekly injection. The main indications for intravitreal therapy were: myelosuppression, kidney toxicity, catheter related sepsis, or refusal of intravenous therapy. The patients were followed for a mean period of 16 weeks (range 8-28 weeks) and received a total of 304 injections. Vitreous foscarnet levels were measured by high performance liquid chromatography. After a 3 week course of induction therapy, complete resolution of the active retinitis was seen in 62.5% (5/8 cases), while 37.5% (3/8 cases) had partial resolution. No cases failed to respond or progress. The rate of relapse on maintenance therapy was 33% (five of 15 eyes) by 20 weeks, and two of these eyes did not respond to reinduction and progressed in involvement of the macula or optic nerve. Neither important local complications nor intraocular drug toxicity were observed. Vitreous foscarnet levels in two different patients were 896 mumol/l and 74.9 mumol/l at 22 3/4 hours and 42 1/2 hours after the injection. Intravitreal foscarnet appears to be a safe, effective, and useful alternative in patients with intolerance to intravenous and viral therapy. PMID:8123619

  15. 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

  16. Flow Injection as a Teaching Tool for Gravimetric Analysis

    NASA Astrophysics Data System (ADS)

    Sartini, Raquel P.; Zagatto, Elias A. G.; Oliveira, Cláudio C.

    2000-06-01

    A flow-injection system to carry out gravimetric analysis is presented. Students are faced with an instrumental approach for gravimetric procedures. Crucibles, muffle furnaces, and desiccators are not required. A flowing suspension is established by simultaneously injecting an aqueous sample and a precipitating reagent into two merging carrier streams. The precipitate is accumulated on a minifilter hanging under the plate of an analytical balance and is weighed inside the main stream. Since Archimedes' principle holds, a drying step is not needed. After measurement, the precipitate is dissolved and disposed of. As an application, the determination of phosphate based on precipitation with ammonium and magnesium ions in slightly alkaline medium is chosen. The proposed system is very stable and well suited for demonstration. When applied to analysis of fertilizer extracts with 0.10-1.00% w/v P, it yields precise results (RSD < 0.042) in agreement with an official spectrophotometric method.

  17. Mathematical analysis of intermittent gas injection model in oil production

    NASA Astrophysics Data System (ADS)

    Tasmi, Silvya, D. R.; Pudjo, S.; Leksono, M.; Edy, S.

    2016-02-01

    Intermittent gas injection is a method to help oil production process. Gas is injected through choke in surface and then gas into tubing. Gas forms three areas in tubing: gas column area, film area and slug area. Gas column is used to propel slug area until surface. A mathematical model of intermittent gas injection is developed in gas column area, film area and slug area. Model is expanding based on mass and momentum conservation. Using assume film thickness constant in tubing, model has been developed by Tasmi et. al. [14]. Model consists of 10 ordinary differential equations. In this paper, assumption of pressure in gas column is uniform. Model consist of 9 ordinary differential equations. Connection of several variables can be obtained from this model. Therefore, dynamics of all variables that affect to intermittent gas lift process can be seen from four equations. To study the behavior of variables can be analyzed numerically and mathematically. In this paper, simple mathematically analysis approach is used to study behavior of the variables. Variables that affect to intermittent gas injection are pressure in upstream valve and in gas column. Pressure in upstream valve will decrease when gas mass in valve greater than gas mass in choke. Dynamic of the pressure in the gas column will decrease and increase depending on pressure in upstream valve.

  18. Joint aspiration and injection and synovial fluid analysis.

    PubMed

    Courtney, Philip; Doherty, Michael

    2009-04-01

    Joint aspiration/injection and synovial fluid (SF) analysis are both invaluable procedures for the diagnosis and treatment of joint disease. This chapter addresses: (1) the indications, the technical principles and the expected benefits and risks of aspiration and injection of intra-articular corticosteroid; and (2) practical aspects relating to SF analysis, especially in relation to crystal identification. Intra-articular injection of long-acting insoluble corticosteroids is a well-established procedure that produces rapid pain relief and resolution of inflammation in most injected joints. The knee is the most common site to require aspiration, although any non-axial joint is accessible for obtaining SF. The technique requires a knowledge of basic anatomy and should not be unduly painful for the patient. Provided sterile equipment and a sensible, aseptic approach are used, it is very safe. Analysis of aspirated SF is helpful in the differential diagnosis of arthritis and is the definitive method for diagnosis of septic arthritis and crystal arthritis. The gross appearance of SF can provide useful diagnostic information in terms of the degree of joint inflammation and presence of haemarthrosis. Microbiological studies of SF are the key to the confirmation of infectious conditions. Increasing joint inflammation is associated with increased SF volume, reduced viscosity, increasing turbidity and cell count, and increasing ratio of polymorphonuclear: mononuclear cells, but such changes are non-specific and must be interpreted in the clinical setting. However, detection of SF monosodium urate and calcium pyrophosphate dihydrate crystals, even from un-inflamed joints during intercritical periods, allow a precise diagnosis of gout and of calcium pyrophosphate crystal-related arthritis. PMID:19393565

  19. Efficacy of combined intravitreal bevacizumab and triamcinolone for branch retinal vein occlusion

    PubMed Central

    Ali, Rasha I; Kapoor, Kapil G; Khan, Adeel N; Gibran, Syed K

    2014-01-01

    Purpose: To evaluate the efficacy of combined treatment with intravitreal bevacizumab (IVB) and triamcinolone acetate (IVT) for patients with macular edema secondary to branch retinal vein occlusion (BRVO). Materials and Methods: Retrospective analysis of 20 eyes injected with 1.25 mg IVB and 2 mg IVT for clinically identified BRVO within 8 weeks of onset. All patients lacked concomitant ocular pathology and completed 6 months’ follow-up. Clinical examination including LogMAR visual acuity (VA) and central macular thickness (CMT) by spectralis optical coherence tomography (OCT) was performed preoperatively and at 1, 3 and 6 months post-operatively. Results: Mean patient age was 61.3 years with a mean BRVO diagnosis time of 3 weeks at presentation. VA improved from logMAR 1.08 preoperatively to Mean logMAR VA of 0.55 ± 0.17 at 1 month (P < 0.001), 0.56 ± 0.21 at 3 months (P < 0.001), and 0.38 ± 0.1 at 6 months (P < 0.001) Mean CMT improved from 482 ± 107 μm preoperatively to 319 ± 53 μm at 1 month (P < 0.001), 344 ± 89 μm at 3 months (P < 0.001), and 241 ± 29 μm at 6 months (P < 0.001). Mean IOP preoperatively was 16.5 mmHg, 21 mmHg at 1 month, and 15 mmHg at 6 months. Six out of 20 patients (30%) were re-injected with IVB and IVT at 3 months. Conclusions: Early combined treatment with IVB and IVT is effective in improving anatomic and functional outcomes in patients with macular edema secondary to BRVO. PMID:24178408

  20. 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

  1. Flow injection analysis with amperometric detection of naltrexone in pharmaceuticals.

    PubMed

    Fernández-Abedul, M T; Costa-García, A

    1997-09-01

    Flow injection analysis (FIA) with amperometric detection using a carbon paste electrode is applied to the determination of naltrexone. The sample solution was injected into the carrier stream of 0.1 M perchloric acid, being determined by oxidation at +1.0 V vs. Ag/AgCl/sat. KCl using a flow rate of 4 ml min-1. A relative standard deviation of 1.5% was calculated for a concentration level of 10(-5) M (n = 17) without carrying out a carbon paste electrode pretreatment. Calibration curves were found to be linear between 2 x 10(-8) and 10(-5) M (almost three orders of magnitude) and the method has a detection limit of 2 x 10(-8) M. A simple and reproducible procedure is proposed for the determination of naltrexone in pharmaceuticals. The results compared favourably with those obtained by an HPLC-UV method. PMID:9447547

  2. Sustained Release Intravitreal Liquid Drug Delivery Using Triamcinolone Acetonide for Cystoid Macular Edema in Retinal Vein Occlusion

    PubMed Central

    Lim, Jennifer I.; Fung, Anne E.; Wieland, Mark; Hung, Dean; Wong, Vernon

    2013-01-01

    Purpose To investigate side effects seen with this formulation and to search for evidence of effectiveness after a single intravitreal injection of IBI-20089 in eyes with cystoid macular edema (CME) secondary to retinal vein occlusion. Design Prospective phase 1 clinical trial Participants 10 patients with chronic CME due to retinal vein occlusion Methods Patients received a single intravitreal injection of IBI-20089 using a sequential dose escalation schedule. Each cohort consisted of five patients who received the intravitreal injection of the sustained liquid drug delivery system containing either 6.9 mg (25 ul) triamcinolone acetonide (TA) (Cohort 1) or 13.8 mg (50 ul) TA (Cohort 2). At each study visit, best corrected visual acuity testing, slit lamp biomicroscopy, intraocular pressure (IOP) measurement, dilated ophthalmoscopy, fundus photography and optical coherence tomography (OCT) were performed. Patients also underwent laboratory testing and physical examinations to monitor for any systemic adverse events. Main Outcome measures OCT central subfield thickness, ocular and systemic adverse events Results In Cohort 1, mean baseline OCT central subfield thickness (CST) was 477 microns (μ) and decreased to 369 μ at day 1 (p< 0.06), 387 μ at day 30 (p= 0.18) and 251 μ at day 360 (p=0.46). In Cohort 2, mean baseline OCT CST was 518 μ, and decreased to 404 μ at day 1 (p=0.134), 289 μ at day 30 (p=0.003), 207 μ at day180 (p=0.004) and 278 μ at day 360 (p=0.009). Related adverse events included elevation of IOP in three patients; two due to neovascular glaucoma (not related to study drug) and one which required a glaucoma tube shunt. Conclusion A single intravitreal injection of IBI-20089 resulted in a controlled and sustained delivery of a TA. Side effects included elevated IOP in three eyes, two of which had neovascular glaucoma. PMID:21397950

  3. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant.

    PubMed

    Giannaccare, Giuseppe; Fresina, Michela; Pazzaglia, Alberto; Versura, Piera

    2016-01-01

    Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional

  4. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant

    PubMed Central

    Giannaccare, Giuseppe; Fresina, Michela; Pazzaglia, Alberto; Versura, Piera

    2016-01-01

    Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional

  5. Effects of intravitreal ropivacaine on retinal thickness and integrity in the guinea pig

    PubMed Central

    Olmez, Gonul; Soker Cakmak, Sevin; Ipek Soker, Sevda; Nergiz, Yusuf; Yildiz, Fethin

    2005-01-01

    Background: Retrobulbar anesthesia is widely used for ocular surgery.Ocular complications are possible when retrobulbar anesthesia is accidentally injected intravitreally. Objective: The aim of this study was to determine the relative retinal toxicitiesof ropivacaine hydrochloride, a local anesthetic, using various concentrations in guinea pigs. Methods: This randomized, investigator-masked, experimental study wasconducted at the Department of Anesthesiology, Dicle University, Diyarbakir, Turkey. The right eyes of 18 guinea pigs were assigned to 1 of 3 treatment groups: 1%, 0.75%, or 0.5% ropivacaine. The right eye of each animal was injected intravitreally with 0.1 mL of 1%, 0.75%, or 0.5% ropivacaine. The left eye of each animal was injected with a balanced saline solution (control). The guinea pigs were euthanized 7 days after injection, and the retinal structures were examined using light microscopy. The total thickness of each retina was measured using an ocular micrometer. Results: No histologic abnormalities were observed in the control eyes.Retinal damage of most of the retinal section was seen in the eyes receiving study drug. The eyes injected with 0.5% ropivacaine had a generally intact appearance, with the exception of some atrophy and disorganization. Overall, the eyes injected with 1% ropivacaine had significantly more extensive retinal thinning compared with the eyes injected with 0.75% or 0.5% ropivacaine (both, P < 0.01). In the eyes injected with 0.75% or 1% ropivacaine, disorganization of the structure of the retinal layers and atrophy were noted on histopathology. The mean total thicknesses of the retina were significantly less in all ropivacaine-treated eyes compared with that in the controls (P < 0.001) Conclusions: In this small experimental study, ropivacaine had concentration-dependent toxic effects on guinea pig retinas. PMID:24672138

  6. Choroidal Neovascularization Associated with Punctate Inner Choroidopathy: Combination of Intravitreal Anti-VEGF and Systemic Immunosuppressive Therapy

    PubMed Central

    Hohberger, Bettina; Rudolph, Michael; Bergua, Antonio

    2015-01-01

    Purpose Choroidal neovascularization (CNV) associated with punctate inner choroidopathy (PIC) is a rare clinical entity, yet still a challenge for medical treatment. A case of a young myopic woman developing CNV secondary to unilateral PIC is presented. Clinical morphology, diagnostic procedure and follow-up are reported. Case Report A 29-year-old woman presented with multiple yellowish dots at the posterior pole. No other signs of inflammation could be seen. Angiography with fluorescein yielded hyperfluorescent signals in the affected areas with a diffuse leak, and SD-OCT showed a slightly elevated retinal pigment epithelial layer, consistent with the diagnosis of PIC. Additionally a classic CNV was observed. Results Anti-inflammatory therapy with local prednisolone acetate eye drops in combination with intravitreal injection of anti-vascular endothelial growth factor (VEGF, bevacizumab) yielded an increased best-corrected visual acuity. As CNV reappeared, systemic medication with prednisone and azathioprine in combination with two further intravitreal injections of anti-VEGF stabilized CNV and increased visual acuity again. Conclusion Combined therapy of immunosuppression with intravitreal anti-VEGF injections can be considered as therapeutic strategy in the management of recurrent CNV associated with PIC. PMID:26955337

  7. Quantitation of glycerophosphorylcholine by flow injection analysis using immobilized enzymes.

    PubMed

    Mancini, A; Del Rosso, F; Roberti, R; Caligiana, P; Vecchini, A; Binaglia, L

    1996-09-20

    A method for quantitating glycerophosphorylcholine by flow injection analysis is reported in the present paper. Glycerophosphorylcholine phosphodiesterase and choline oxidase, immobilized on controlled porosity glass beads, are packed in a small reactor inserted in a flow injection manifold. When samples containing glycerophosphorylcholine are injected, glycerophosphorylcholine is hydrolyzed into choline and sn-glycerol-3-phosphate. The free choline produced in this reaction is oxidized to betain and hydrogen peroxide. Hydrogen peroxide is detected amperometrically. Quantitation of glycerophosphorylcholine in samples containing choline and phosphorylcholine is obtained inserting ahead of the reactor a small column packed with a mixed bed ion exchange resin. The time needed for each determination does not exceed one minute. The present method, applied to quantitate glycerophosphorylcholine in samples of seminal plasma, gave results comparable with those obtained using the standard enzymatic-spectrophotometric procedure. An alternative procedure, making use of co-immobilized glycerophosphorylcholine phosphodiesterase and glycerol-3-phosphate oxidase for quantitating glycerophosphorylcholine, glycerophosphorylethanolamine and glycerophosphorylserine is also described. PMID:8905629

  8. Esophageal Metastasis to the Iris Effectively Palliated Using Stereotactic Body Radiation Therapy and Adjuvant Intravitreal Chemotherapy: Case Report and Literature Review

    PubMed Central

    Dhakal, Sughosh; Lema, Gareth M.C.; DiLoreto, David A.; Katz, Alan W.

    2012-01-01

    We report a case of isolated iris metastasis from esophageal adenocarcinoma that was successfully managed with local application of stereotactic body radiation therapy (SBRT) and adjunctive intravitreal therapy. A 53-year-old man with locally advanced esophageal adenocarcinoma achieved a complete clinical and radiographic response after surgery and chemotherapy. Four months later, he developed headache and decreased vision and was diagnosed with metastasis to the iris by slit-lamp examination. The decrease in vision was secondary to cystoid macular edema. The metastatic tumor and the patient's symptoms resolved after treatment with SBRT and intravitreal injections of bevacizumab and triamcinolone. We conclude that SBRT combined with intravitreal chemotherapy is an effective and well-tolerated palliative treatment for metastasis of esophageal adenocarcinoma to the iris. PMID:23275779

  9. High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration

    PubMed Central

    Lee, Dong Kyu; Kim, Soon Hyun; You, Yong Sung

    2016-01-01

    Purpose 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. Methods 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. Results 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. Conclusions Increasing the dose of bevacizumab in refractory PED may be a possible treatment option. PMID:27478353

  10. Systemic and Intravitreal Delivery of Dendrimers to Activated Microglia/Macrophage in Ischemia/Reperfusion Mouse Retina

    PubMed Central

    Kambhampati, Siva P.; Clunies-Ross, Alexander J. M.; Bhutto, Imran; Mishra, Manoj K.; Edwards, Malia; McLeod, D. Scott; Kannan, Rangaramanujam M.; Lutty, Gerard

    2015-01-01

    Purpose Microglial activation and associated neuroinflammation play a key role in the pathogenesis of many diseases of the retina, including viral infection, diabetes, and retinal degeneration. Strategies to target activated microglia and macrophages and attenuate inflammation may be valuable in treating these diseases. We seek to develop dendrimer-based formulations that target retinal microglia and macrophages in a pathology-dependent manner, and deliver drugs, either intravenously or intravitreally. Methods Retinal uptake of cyanine dye (Cy5)-conjugated dendrimer (D-Cy5) was assessed in normal and ischemia/reperfusion (I/R) mouse eyes. Microglia/macrophage uptake of the dendrimer was assessed with immunofluorescence using rabbit Iba-1 antibody with Cy3-tagged secondary antibody (microglia/macrophage). Uptake in retina and other organs was quantified using fluorescence spectroscopy. Results Clearance of D-Cy5 from normal eyes was almost complete by 72 hours after intravitreal injection and 24 hours after intravenous delivery. In eyes with activated microglia after I/R injury, D-Cy5 was retained by activated microglia/macrophage (Iba1+ cells) up to 21 days after intravitreal and intravenous administration. In I/R eyes, the relative retention of intravitreal and intravenous D-Cy5 was comparable, if a 30-fold higher intravenous dose was used. Conclusions Intravitreal and systemic dendrimers target activated microglia and show qualitatively similar retinal biodistribution when administered by either route. Results provide proof-of-concept insights for developing dendrimer drug formulations as treatment options for retinal diseases associated with microglia or macrophage activation such as age-related macular degeneration, diabetic retinopathy, and retinal degenerations. PMID:26193917

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

    PubMed Central

    Zhang, Hai-Tao; Yang, Yu-Xin; Xu, Ying-Ying; Yang, Rui-Min; Wang, Bao-Jun; Hu, Jun-Xi

    2014-01-01

    AIM To explore the efficacy of preoperative intravitreal bevacizumab (IVB) injection combined with Ahmed glaucoma valve (AGV) implantation in the treatment of neovascular glaucoma (NVG). METHODS This retrospective study included 35 eyes from 35 patients who underwent preoperative IVB and AGV implantation for treatment of NVG. Findings such as intraocular pressure (IOP) number of anti-glaucoma medications, visual acuity (VA), surgical success rates, and complications were recorded. RESULTS After AGV implantation, IOP was 18.2±4.0 mm Hg, 15.5±3.3 mm Hg and 9.8±2.6 mm Hg at 6, 12 and 36mo, significantly decreased compared with pre-IOP (P<0.01). The number of anti-glaucoma medications was 0.9±0.5, 0.8±0.9 and 0.8±0.6 at 6, 12 and 36mo, significantly decreased compared to pre-treatment (P<0.01). At last visit, there were 19 eyes with stable VA, 4 with VA improvement, 12 with diminished VA and 3 with complete loss light perception. There were 7 cases that failed during 3-year fellow up period. Cumulative probabilities of valve survival by Kaplan-Meier analysis were 82.9%, 74.1% and 71.0% at 12, 24 and 36mo, respectively. Cox stepwise regression analysis found that the survival time was significant associated with the pre-visual acuity <2/400 (P<0.05). Post-operative complications occurred in 8 eyes, of which hyphema presented in 2 eyes, choroidal effusion in 2 eyes. CONCLUSION The procedure of preoperative IVB and AGV implantation should be one of treatments for NVG because of its safety and effectiveness. PMID:25349803

  12. 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

  13. Evaluation of Intravitreal Ranibizumab on the Surgical Outcome for Diabetic Retinopathy With Tractional Retinal Detachment.

    PubMed

    Dong, Feng; Yu, Chenying; Ding, Haiyuan; Shen, Liping; Lou, Dinghua

    2016-02-01

    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 treatment of

  14. 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.

  15. Hypotension Associated With Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity.

    PubMed

    Wu, Lu-Hsuan; Yang, Yea-Huei Kao; Lin, Chyi-Her; Lin, Yuh-Jyh; Cheng, Ching-Lan

    2016-02-01

    Intravitreal bevacizumab therapy in preterm infants for retinopathy of prematurity (ROP) can be associated with hypotension. We report twin preterm infants who developed hypotension within 1 day after intravitreal bevacizumab therapy for ROP. Before receiving the medication, their clinical statuses were stable and similar. The dose, procedure, and premedication were the same; however, twin B presented with hypotension for 3 days. Although bevacizumab-related hypotension has been described in product information (incidence rate 7%-15%), this is the first case report of intravitreal bevacizumab for ROP inducing hypotension. Physicians should be aware of intravitreal bevacizumab therapy-related hypotension when treating ROP. We suggest conducting a postmarketing active surveillance on the systemic adverse effects of this regimen in preterm infants. PMID:26743817

  16. 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

  17. 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

  18. 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.

  19. Longitudinal Changes in Retinal Nerve Fiber Layer Thickness after Intravitreal Anti-vascular Endothelial Growth Factor Therapy

    PubMed Central

    Jo, Young-Joon; Kim, Woo-Jin; Shin, Il-Hwan

    2016-01-01

    Purpose To determine the effects of intravitreal anti-vascular endothelial growth factor (VEGF) on thickness of the retinal nerve fiber layer (RNFL) in patients with age-related macular degeneration. Methods Twenty eyes of 20 patients diagnosed with age-related macular degeneration who underwent intravitreal anti-VEGF injection were studied. Postinjection RNFL thickness was measured using optical coherence tomography. Average thickness, four-quadrant RNFL thicknesses, and intraocular pressure (IOP) in affected eyes were measured before and 6 and 12 months after anti-VEGF injection for comparison. RNFL thickness and IOP in affected and normal fellow eyes were also compared. Given that macular lesions can affect RNFL thickness, the changes in thickness were evaluated by dividing the 12 clock-hour RNFL into the pathologic areas adjacent to the lesion and the non-pathologic area. Results The mean clock-hour segment in the pathologic area was 4.8 hours. A significantly thicker RNFL was exhibited in temporal quadrants and pathologic areas (p = 0.043 and 0.048, respectively) in affected eyes before injection compared to the baseline RNFL thickness in normal eyes. No significant differences were found in RNFL thickness or IOP between affected and normal eyes after injection. The changes over time in the temporal and pathologic areas were statistically significant at 6 and 12 months after injection compared to baseline data (p < 0.05). No significant differences were displayed in RNFL thickness in the other three quadrants or in non-pathologic areas in either affected or normal eyes. Sequential changes in RNFL thickness in affected eyes were not significant. Conclusions Repeat intravitreal anti-VEGF treatment did not have a significant effect on RNFL thickness. RNFL thickness significantly decreased with time in the pathologic areas and in the temporal segment adjacent to exudative macular lesions. The reduction in RNFL thickness was most likely associated with changes in

  20. Residual aqueous ozone determination by gas diffusion flow injection analysis

    SciTech Connect

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

    1985-08-01

    A method for the determination of residual aqueous ozone utilizing the technique of gas diffusion flow injection analysis and the redox reagents potassium indigo trisulfonate and bis(terpyridine)iron(II) is described. The system uses a commercially available gas diffusion cell fitted with a microporous Teflon membrane to significantly reduce or eliminate potential interferences such as chlorine and oxidized forms of manganese. Detection limits of 0.03 mg/L ozone are possible with sensitivities and linear ranges comparable to the manual method. Selectivity is significantly improved and chlorine interference is reduced to 0.008 mg/L of apparent ozone for each part per million of chlorine present while oxidized manganese interference is completely eliminated. This method provides a sample throughput of 65 samples per hour. 30 references, 2 figures, 2 tables.

  1. 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.

  2. Intravitreal bevacizumab in the successful management of choroidal metastases secondary to lung and breast cancer unresponsive to systemic therapy: a case series

    PubMed Central

    Fenicia, V; Abdolrahimzadeh, S; Mannino, G; Verrilli, S; Balestrieri, M; Recupero, S M

    2014-01-01

    Purpose Management of choroidal metastases is commonly with systemic chemotherapy; however, if tumours are refractory to treatment and vision is endangered, local therapy modalities are feasible. A novel option is the use of intravitreal bevacizumab. This report presents three cases of choroidal metastatic tumours secondary to lung and breast cancer treated with intravitreal bevazizumab. Patients and methods Three patients with choroidal metastases secondary to lung and breast tumours were treated at the Ophthalmology Unit, University of Rome ‘Sapienza', S.Andrea Hospital from January 2009 to August 2012. All patients developed vision loss with diagnosis of chorioidal metastasis during systemic chemotherapy. Off label intravitreal bevacizumab treatment was performed with two 1.25 mg injections in two patients and four injections in one patient at 30-day intervals. Results Vision improved, subretinal fluid resolved, and choroidal tumour regression was obtained in all cases. Follow-up was 6, 9, and 12 months and there were no complications related to treatment. Conclusions Intravitreal bevacizumab administration represented an efficacious therapeutic option with rapid effect in the treatment of choroidal metastatic tumours unresponsive to systemic therapy. It can have a role in the management of these tumours by preventing vision loss and improving the quality of life of patients. PMID:24763241

  3. Analysis of thermally induced permeability enhancement in geothermal injection wells

    SciTech Connect

    Benson, S.M.; Daggett, J.S.; Iglesias, E.; Arellano, V.; Ortiz-Ramirez, J.

    1987-02-01

    Reinjection of spent geothermal brine is a common means of disposing of geothermal effluents and maintaining reservoir pressures. Contrary to the predictions of two-fluid models (two-viscosity) of nonisothermal injection, an increase of injectivity, with continued injection, is often observed. Injectivity enhancement and thermally-affected pressure transients are particularly apparent in short-term injection tests at the Los Azufres Geothermal Field, Mexico. During an injection test, it is not uncommon to observe that after an initial pressure increase, the pressure decreases with time. As this typically occurs far below the pressure at which hydraulic fracturing is expected, some other mechanism for increasing the near-bore permeability must explain the observed behavior. This paper focuses on calculating the magnitude of the nearbore permeability changes observed in several nonisothermal injection tests conducted at the Los Azufres Geothermal Field.

  4. Controlled Release of Dexamethasone From an Intravitreal Delivery System Using Porous Silicon Dioxide

    PubMed Central

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

    2016-01-01

    Purpose The current study aims to evaluate a porous silicon-based drug delivery system meant for sustained delivery of dexamethasone (Dex) to the vitreous and retina. Methods Dexamethasone was grafted covalently into the pore walls of fully oxidized porous silicon particles (pSiO2-COO-Dex), which then was evaluated for the pharmacological effect of the payload on cultured ARPE19 cells before intravitreal injection. The Dex release profile was investigated in a custom designed dynamic dissolution chamber to mimic the turnover of vitreous fluid in rabbit eyes. Ocular safety, in vivo release, and pharmacodynamics were evaluated in rabbit eyes, and the human VEGF-induced rabbit retinal vascular permeability model. Results Loading efficiency of Dex was 69 ± 9 μg per 1 mg of the pSiO2-COO-Dex particles. Dynamic in vitro release demonstrated a sustained mode when compared to free Dex, with the drug half-life extended by 5 times. The released Dex was unaltered and biologically active. In vivo drug release in rabbit eyes revealed a mode similar to the release seen in vitro, with a vitreous half-life of 11 days. At 2 and 4 weeks after a single intravitreal injection of pSiO2-COO-Dex particles (mean 2.71 ± 0.47 mg), intravitreal 500 ng of VEGF did not induce significant retinal vessel dilation or fluorescein leakage, while these events were observed in the eyes injected with empty pSiO2 particles or with free Dex. The retinal vessel score from fluorescein angiography for the control eyes was double the score for the eyes injected with pSiO2-COO-Dex. No adverse reaction was observed for the eyes injected with drug-loaded pSi particles during the course of the study. Conclusions The porous silicon-based Dex delivery system (pSiO2-COO-Dex) can be administered safely into vitreous without toxicity. Dex release from the porous silicon particles was sustained for 2 months and was effective against VEGF-induced retinal vessel reaction. PMID:26882530

  5. 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

  6. Randomized Clinical Trial Evaluating Intravitreal Ranibizumab or Saline for Vitreous Hemorrhage from Proliferative Diabetic Retinopathy

    PubMed Central

    Bhavsar, Abdhish R.; Torres, Karisse; Beck, Roy W.; Bressler, Neil M.; Ferris, Frederick L.; Friedman, Scott M.; Glassman, Adam R.; Maturi, Raj K.; Melia, Michele; Singer, Michael A.; Stockdale, Cynthia R.

    2014-01-01

    Objective To evaluate intravitreal ranibizumab compared with intravitreal saline injections on vitrectomy rates for vitreous hemorrhage (VH) from proliferative diabetic retinopathy (PDR). Main Outcome Cumulative probability of vitrectomy within 16 weeks. Methods Study eyes had VH from PDR precluding panretinal photocoagulation (PRP) completion. Eyes were randomly assigned to 0.5-mg ranibizumab (N = 125) or saline (N = 136) at baseline, 4, and 8 weeks. Results Cumulative probability of vitrectomy by 16 weeks was 12% with ranibizumab versus 17% with saline (difference 4%, 95% confidence interval −4%–13%) and of complete PRP without vitrectomy by 16-weeks was 44% and 31% respectively (P = 0.05). The mean (±SD) visual acuity improvement from baseline to 12 weeks was 22±23 letters and 16±31 letters respectively (P = 0.04). Recurrent VH occurred within 16 weeks in 6% and 17% respectively (P = 0.01). One eye developed endophthalmitis after saline. Conclusions Overall the 16 week vitrectomy rates were lower than expected in both groups. This study suggests little likelihood of a clinically important difference between ranibizumab and saline on the rate of vitrectomy by 16 weeks in eyes with VH from PDR. Short term secondary outcomes including visual acuity improvement, increased PRP completion rates, and reduced recurrent VH rates suggest biologic activity of ranibizumab. Long term benefits remain unknown. Whether vitrectomy rates after saline or ranibizumab are different than observation alone cannot be determined from this study. Application to Clinical Practice Intravitreal ranibizumab does not appear to reduce vitrectomy rates compared with saline for VH from PDR. PMID:23370902

  7. Intravitreal ranibizumab for bilateral choroidal neovascularisation in a patient with angioid streaks

    PubMed Central

    Yilmaz, Ihsan; Ozkaya, Abdullah; Alkin, Zeynep; Yazici, Ahmet Taylan

    2014-01-01

    Angioid streaks are described as irregular lines deep into the retina, configured in a radiating fashion which results from breaks in Bruch’s membrane. Optic nerve head drusen are acellular, globular deposits located within the optic nerve head. Angioid streaks and optic nerve head drusen may coexist in patients with pseudoxanthoma elasticum. Both disorders may cause choroidal neovascularisation. In this case report we aimed to present a 48-year-old man with pseudoxanthoma elasticum. The patient had bilateral choroidal neovascularisation secondary to angioid streaks and was treated with intravitreal ranibizumab injections. Visual acuity was increased and maintained at the same level during the follow-up time. There was no complication related to the injection. PMID:25073527

  8. Spectral Analysis Software for the Compact Toroid Injection Experiment

    NASA Astrophysics Data System (ADS)

    Belknap, Donald

    2009-11-01

    The Compact Toroid Injection Experiment (CTIX) operated by UC Davis functions by producing a spheromak-like plasma which is accelerated via a coaxial railgun. In order to examine features of the plasma such as impurities and temperature, the spectrum of the plasma is measured during a shot. Because of the number of shots that may be taken in a single day, a computer analysis program is an expedient method of analyzing the spectra. A graphic user interface (GUI) was designed to allow the user to easily read the spectral images from an archived data file and interactively perform functions such as CCD camera tilt correction, background subtraction, and wavelength calibration. The code for the GUI, background subtraction, wavelength calibration, and tilt correction algorithms are written in a high-level programming language, Igor, to allow for easy extension by CTIX scientists. The code can be extended to add features that can perform analysis on large numbers of spectra. Results of CTIX shots and calibration spectra will be presented.

  9. Simultaneous determination of three species with a single-injection step using batch injection analysis with multiple pulse amperometric detection.

    PubMed

    Freitas, Jhonys Machado; Oliveira, Thiago da Costa; Gimenes, Denise Tofanello; Munoz, Rodrigo Alejandro Abarza; Richter, Eduardo Mathias

    2016-01-01

    In this work, the possibility of simultaneous determination of three compounds with a single-injection step using batch injection analysis with multiple pulse amperometric detection (BIA-MPA) is demonstrated for the first time. A sequence of three potential pulses (+1.25 V, +1.60 V, and +1.80 V) was applied with the acquisition of three separate amperograms. 8-Chlorotheophylline was detected selectively at +1.25 V, both 8-chlorotheophylline and pyridoxine at +1.60V and 8-chlorotheophylline, pyridoxine, and diphenhydramine at +1.80 V. Subtraction between the currents detected at the three amperograms (with the help of correction factors) was used for the selective determination of pyridoxine and diphenhydramine. The proposed method is simple, inexpensive, fast (60 injections h(-1)), and present selectivity for the determination of the three compounds in pharmaceutical samples, with results similar to those obtained by HPLC (95% confidence level). PMID:26695316

  10. Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration.

    PubMed

    Rodríguez Villanueva, Javier; Bravo-Osuna, Irene; Herrero-Vanrell, Rocío; Molina Martínez, Irene Teresa; Guzmán Navarro, Manuel

    2016-09-20

    Successful therapy for chronic diseases affecting the posterior segment of the eye requires sustained drug concentrations at the site of action for extended periods of time. To achieve this, it is necessary to use high systemic doses or frequent intraocular injections, both associated with serious adverse effects. In order to avoid these complications and improve patient's quality of life, an experimental study has been conducted on the preparation of a new generation of biodegradable poly(D,L-lactide-co-glycolide) (50:50) (PLGA) polymer microspheres (MSs) loaded with Dxm, vitamin E and/or human serum albumin (HSA). Particles were prepared according to a S/O/W encapsulation method and the 20-40μm fraction was selected. This narrow size distribution is suitable for minimally invasive intravitreal injection by small calibre needles. Characterisation of the MSs showed high Dxm loading and encapsulation efficiency (> 90%) without a strong interaction with the polymer matrix, as revealed by DSC analysis. MSs drug release studies indicated a small burst effect (lower than 5%) during the first five hours and subsequently, drug release was sustained for at least 30days, led by diffusion and erosion mechanisms. Dxm release rate was modulated when solid state HSA was incorporated into MSs formulation. SDS-PAGE analysis showed that the protein maintained its integrity during the encapsulation process, as well as for the release study. MSs presented good tolerance and lack of cytotoxicity in macrophages and HeLa cultured cells. After 12months of storage under standard refrigerated conditions (4±1°C), MSs retained appropriate physical and chemical properties and analogous drug release kinetics. Therefore, we conclude that these microspheres are promising pharmaceutical systems for intraocular administration, allowing controlled release of the drug. PMID:26987610

  11. Development, Characterizations and Biocompatibility Evaluations of Intravitreal Lipid Implants

    PubMed Central

    Tamaddon, Lana; Mostafavi, Abolfazl; Riazi-esfahani, Mohammad; Karkhane, Reza; Aghazadeh, Sara; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid; Asadi Amoli, Fahimeh

    2014-01-01

    Background: The treatment of posterior eye diseases is always challenging mainly due to inaccessibility of the region. Many drugs are currently delivered by repeated intraocular injections. Objectives: The purpose of this study was to investigate the potential applications of natural triglycerides as alternative carriers to synthetic polymers in terms of drug release profile and also biocompatibility for intraocular use. Materials and Methods: In vitro/in vivo evaluations of intravitreal implants fabricated from the physiological lipid, glyceride tripalmitate containing clindamycin phosphate as a model drug was performed. The micro-implants with average diameter of 0.4 mm were fabricated via a hot melt extrusion method. The extrudates were analyzed using scanning electron microscopy, differential scanning calorimetry, and in vitro drug dissolution studies. For biocompatibility, the implants were implanted into rabbit eyes. Clinical investigations including fundus observations, electroretinography as well as histological evaluations were performed. Results: In vitro tests guaranteed usefulness of the production method for preparing the homogenous mixture of the drug and lipid without affecting thermal and crystalinity characteristics of the components. In vitro releases indicated a bi-phasic pattern for lower lipid ratios, which were completed by the end of day three. With higher lipid ratios, more controlled release profiles were achieved until about ten days for a lipid ratio of 95%. Clinical observations did not show any abnormalities up to two months after implantation into the rabbit eye. Conclusions: These results suggest that although the implant could not adequately retard release of the present drug model yet, due to good physical characteristics and in vivo biocompatibility, it can represent a suitable device for loading wide ranges of therapeutics in treatment of many kinds of retinochoroidal disorders. PMID:24872944

  12. The Efficacy and Safety of Current Treatments in Diabetic Macular Edema: A Systematic Review and Network Meta-Analysis

    PubMed Central

    Zhang, Lu; Wang, Wen; Gao, Yan; Lan, Jie; Xie, Lixin

    2016-01-01

    Purpose To compare the efficacy and safety of current treatments in diabetic macular edema (DME). Methods PubMed, Embase and CENTRAL were systematically reviewed for randomized controlled trials of current treatments in DME through August 2015. Data on the mean change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) were extracted, and adverse events (AEs) were collected. Results A total of 21 trials were included in our network meta-analysis. Intravitreal ranibizumab improved BCVA most significantly (OR: +7.01 95%CI (2.56 to 11.39)) in 6 months and intravitreal aflibercept (+8.19 (5.07 to 11.96)) in 12 months. Intravitreal triamcinolone combined with LASER decreased CMT most significantly (-111.34 (-254.61 to 37.93)) in 6 months and intravitreal aflibercept (-110.83 (-190.25 to -35.27)) in 12 months. Compared with the relatively high rate of ocular AEs in the groups with administration of steroids, systematic AEs occurred more frequently in the groups with vascular endothelial growth factor inhibitors involved. Conclusions Our analysis confirms that intravitreal aflibercept is most favorable with both BCVA improvement and CMT decrease than other current therapies in the management of DME within 12 months. Vascular endothelial growth factor inhibitors for DME should be used with caution due to systematic AEs. Combined intravitreal triamcinolone with LASER has a stronger efficacy in decreasing CMT than the other interventions in the early stage after injection. More high-quality randomized controlled trials will be necessary. PMID:27434498

  13. Coating nanocarriers with hyaluronic acid facilitates intravitreal drug delivery for retinal gene therapy.

    PubMed

    Martens, Thomas F; Remaut, Katrien; Deschout, Hendrik; Engbersen, Johan F J; Hennink, Wim E; van Steenbergen, Mies J; Demeester, Jo; De Smedt, Stefaan C; Braeckmans, Kevin

    2015-03-28

    Retinal gene therapy could potentially affect the lives of millions of people suffering from blinding disorders. Yet, one of the major hurdles remains the delivery of therapeutic nucleic acids to the retinal target cells. Due to the different barriers that need to be overcome in case of topical or systemic administration, intravitreal injection is an attractive alternative administration route for large macromolecular therapeutics. Here it is essential that the therapeutics do not aggregate and remain mobile in the vitreous humor in order to reach the retina. In this study, we have evaluated the use of hyaluronic acid (HA) as an electrostatic coating for nonviral polymeric gene nanomedicines, p(CBA-ABOL)/pDNA complexes, to provide them with an anionic hydrophilic surface for improved intravitreal mobility. Uncoated polyplexes had a Z-averaged diameter of 108nm and a zeta potential of +29mV. We evaluated polyplexes coated with HA of different molecular weights (22kDa, 137kDa and 2700kDa) in terms of size, surface charge and complexation efficiency and noticed their zeta potentials became anionic at 4-fold molar excess of HA-monomers compared to cationic monomers, resulting in submicron ternary polyplexes. Next, we used a previously optimized ex vivo model based on excised bovine eyes and fluorescence single particle tracking (fSPT) microscopy to evaluate mobility in intact vitreous humor. It was confirmed that HA-coated polyplexes had good mobility in bovine vitreous humor, similar to polyplexes functionalized with polyethylene glycol (PEG), except for those coated with high molecular weight HA (2700kDa). However, contrary to PEGylated polyplexes, HA-coated polyplexes were efficiently taken up in vitro in ARPE-19 cells, despite their negative charge, indicating uptake via CD44-receptor mediated endocytosis. Furthermore, the HA-polyplexes were able to induce GFP expression in this in vitro cell line without apparent cytotoxicity, where coating with low molecular

  14. Remote calorimetric detection of urea via flow injection analysis.

    PubMed

    Gaddes, David E; Demirel, Melik C; Reeves, W Brian; Tadigadapa, Srinivas

    2015-12-01

    The design and development of a calorimetric biosensing system enabling relatively high throughput sample analysis are reported. The calorimetric biosensor system consists of a thin (∼20 μm) micromachined Y-cut quartz crystal resonator (QCR) as a temperature sensor placed in close proximity to a fluidic chamber packed with an immobilized enzyme. Layer by layer enzyme immobilization of urease is demonstrated and its activity as a function of the number of layers, pH, and time has been evaluated. This configuration enables a sensing system where a transducer element is physically separated from the analyte solution of interest and is thereby free from fouling effects typically associated with biochemical reactions occuring on the sensor surface. The performance of this biosensing system is demonstrated by detection of 1-200 mM urea in phosphate buffer via a flow injection analysis (FIA) technique. Miniaturized fluidic systems were used to provide continuous flow through a reaction column. Under this configuration the biosensor has an ultimate resolution of less than 1 mM urea and showed a linear response between 0-50 mM. This work demonstrates a sensing modality in which the sensor itself is not fouled or contaminated by the solution of interest and the enzyme immobilized Kapton® fluidic reaction column can be used as a disposable cartridge. Such a system enables reuse and reliability for long term sampling measurements. Based on this concept a biosensing system is envisioned which can perform rapid measurements to detect biomarkers such as glucose, creatinine, cholesterol, urea and lactate in urine and blood continuously over extended periods of time. PMID:26479269

  15. 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. PMID:27274319

  16. 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 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. PMID:27274319

  17. DETERMINATION OF PH BY FLOW INJECTION ANALYSIS AND BY FIBER OPTRODE ANALYSIS

    EPA Science Inventory

    Two new procedures for measuring pH have been developed. The first measures pH colorimetrically using a proprietary indicator dye mixture in a flow injection analysis (FIA) procedure. The second measures pH using a fiber optic chemical sensor (FOCS) specifically developed for pH ...

  18. Two-year results of intravitreal ranibizumab for polypoidal choroidal vasculopathy with recurrent or residual exudation

    PubMed Central

    Saito, M; Iida, T; Kano, M; Itagaki, K

    2013-01-01

    Aim To clarify the 2-year efficacy of ranibizumab for patients with polypoidal choroidal vasculopathy (PCV) with recurrent or residual exudation from branching vascular networks after previous photodynamic therapy (PDT). Methods We retrospectively reviewed 26 eyes of 26 Japanese patients (22 men, 4 women) in this pilot study. All eyes had PCV with complete regression of polypoidal lesions resulting from PDT detected by indocyanine green angiography (ICGA), but recurrent or residual leakage from branching vascular networks on fluorescein angiography and evidence of persistent fluid on optical coherence tomography (OCT). Three consecutive intravitreal injections of ranibizumab (0.5 mg/0.05 ml) were administered to all eyes. Results The mean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) improved significantly from 0.55 at baseline to 0.35 at 12 months (P<0.0001) and 0.43 at 24 months (P=0.0012). The mean increases in the BCVA 12 and 24 months after baseline were 1.95 and 1.23 lines, respectively. The mean central retinal thickness significantly decreased from 295 μm at baseline to 189 μm at 12 months (P<0.0038) and 163 μm at 24 months (P<0.001). The mean numbers of intravitreal ranibizumab (IVR) injections at months 12 and 24, including the initial treatments, were 5.8 and 8.8, respectively. Five (19.2%) eyes had recurrent polypoidal lesions on ICGA at a mean of 15.7 months after baseline. At month 24, OCT showed no exudation in 17 (65.4%) of the 26 eyes. No adverse events developed. Conclusions IVR injections maintained or improved the VA and retinal thickness at 24 months in eyes with PCV with recurrent or residual exudation from branching vascular networks after previous PDT. PMID:23743532

  19. Morphologic Changes in Patient with Drusen and Drusenoid Pigment Epithelial Detachment after Intravitreal Ranibizumab for Choroidal Neovascular Membrane : A Case Report.

    PubMed

    Kim, Sukjin; Oh, Jeongjae; Kim, Kiseok

    2016-01-01

    The authors present a case of morphologic changes of drusen and drusenoid pigment epithelial detachment (DPED) after treating choroidal neovascularization (CNV) using ranibizumab in age-related macular degeneration (AMD). A 71-year-old woman has noticed mild visual acuity deterioration in the right eye for several months. She was presented with some drusen and DPED associated with CNV. This patient was given intravitreal injection of 0.5 mg of ranibizumab five times at monthly intervals for treating CNV. DPED in the temporal and drusen in the superior to macula were diminished, which continued up to 2 months. Intravitreal ranibizumab injection may have influenced with diminishment of drusen and DPED. After 2 months, CNV was recurred. PMID:27014379

  20. Morphologic Changes in Patient with Drusen and Drusenoid Pigment Epithelial Detachment after Intravitreal Ranibizumab for Choroidal Neovascular Membrane : A Case Report

    PubMed Central

    Kim, Sukjin; Oh, Jeongjae; Kim, Kiseok

    2016-01-01

    The authors present a case of morphologic changes of drusen and drusenoid pigment epithelial detachment (DPED) after treating choroidal neovascularization (CNV) using ranibizumab in age-related macular degeneration (AMD). A 71-year-old woman has noticed mild visual acuity deterioration in the right eye for several months. She was presented with some drusen and DPED associated with CNV. This patient was given intravitreal injection of 0.5 mg of ranibizumab five times at monthly intervals for treating CNV. DPED in the temporal and drusen in the superior to macula were diminished, which continued up to 2 months. Intravitreal ranibizumab injection may have influenced with diminishment of drusen and DPED. After 2 months, CNV was recurred. PMID:27014379

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

    PubMed Central

    Wang, Mei-Zi; Feng, Kang; Lu, Yao; Qian, Fang; Lu, Xin-Rong; Zang, Si-Wen; Zhao, Lin

    2016-01-01

    AIM To investigate the predictive factors for short-term effects of intravitreal bevacizumab injections on central subfield foveal thickness (CSFT) in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS This was a retrospective study in 60 eyes treated with intravitreal bevacizumab injections for ME due to CRVO. Follow-up was three months. The Early Treatment Diabetic Retinopathy Study (ETDRS) score and CSFT measured by spectral-domain optical coherence tomography (SD-OCT) were used to observe the changes in best-corrected visual acuity (BCVA). Baseline BCVA, CSFT, age, CRVO duration and the presence of cystoid macular edema (CME) or subretinal fluid (SRF) were analyzed as potential predictive factors of the effects of intravitreal bevacizumab injections. RESULTS BCVA improved from 0.9 logMAR at baseline to 0.6 logMAR at 3mo, which was associated with a significant reduction in CSFT from 721 µm to 392 µm 3mo after injection. About 50% of CME cases and more than 90% of SRF cases responded to treatment with a complete resolution at 3mo. Age (P=0.036) and low baseline CSFT (P=0.037) were associated with a good 3-month prognosis. Patients >60 years old achieved better CME resolution (P=0.031) and lower CSFT at 3mo (305 µm vs 474 µm, P=0.003). CONCLUSION Intravitreal bevacizumab significantly improved visual acuity and CSFT in patients with CRVO after 3mo. Older age and lower baseline CSFT were good predictors of short-term CSFT outcomes. The retinal thickness response to bevacizumab might depend on the resolution of CME rather than SRF. PMID:26949616

  2. The effect of intravitreal vascular endothelial growth factor on inner retinal oxygen delivery and metabolism in rats.

    PubMed

    Blair, Norman P; Wanek, Justin; Teng, Pang-yu; Shahidi, Mahnaz

    2016-02-01

    Vascular endothelial growth factor (VEGF) is stimulated by hypoxia and plays an important role in pathologic vascular leakage and neovascularization. Increased VEGF may affect inner retinal oxygen delivery (DO2) and oxygen metabolism (MO2), however, quantitative information is lacking. We tested the hypotheses that VEGF increases DO2, but does not alter MO2. In 10 rats, VEGF was injected intravitreally into one eye, whereas balanced salt solution (BSS) was injected into the fellow eye, 24 h prior to imaging. Vessel diameters and blood velocities were determined by red-free and fluorescent microsphere imaging, respectively. Vascular PO2 values were derived by phosphorescence lifetime imaging of an intravascular oxyphor. Retinal blood flow, vascular oxygen content, DO2 and MO2 were calculated. Retinal arterial and venous diameters were larger in VEGF-injected eyes compared to control eyes (P < 0.03), however no significant difference was observed in blood velocity (P = 0.21). Thus, retinal blood flow was greater in VEGF-injected eyes (P = 0.007). Retinal vascular PO2 and oxygen content were similar between control and VEGF-injected eyes (P > 0.11), while the arteriovenous oxygen content difference was marginally lower in VEGF-injected eyes (P = 0.05). DO2 was 950 ± 340 and 1380 ± 650 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.005). MO2 was 440 ± 150 and 490 ± 190 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.31). Intravitreally administered VEGF did not alter MO2 but increased DO2, suggesting VEGF may play an offsetting role in conditions characterized by retinal hypoxia. PMID:26518179

  3. Incidence of Endophthalmitis after Intravitreal Anti-vascular Endothelial Growth Factor: Experience in Saudi Arabia

    PubMed Central

    Al-Rashaed, Saba; Alsulaiman, Sulaiman M.; Alrushood, Abdulaziz Adel; Almasaud, Jluwi; Arevalo, J. Fernando

    2016-01-01

    Purpose: To report the incidence of endophthalmitis, the clinical and microbiological aspects, after intravitreal (IVT) injection of anti-vascular endothelial growth factor. Methods: A chart review was performed of patients diagnosed with endophthalmitis after receiving IVT injections of bevacizumab (Avastin) and ranibizumab (Lucentis) presenting to King Khaled Eye Specialist Hospital (KKESH) from May 2006 to December 2012. Endophthalmitis was diagnosed clinically as an intraocular infection with vitreous involvement that required treatment with IVT antibiotics or had undergone pars plana vitrectomy (PPV) to remove the suspected microorganism. Main outcome measures were the incidence of endophthalmitis and the clinical and microbiological features. Results: Seven cases of endophthalmitis were identified, there was 1 (0.004%) case of endophthalmitis of 22674 IVT injections performed at KKESH. All cases were after IVT bevacizumab. Three (42.85%) cases were culture-positive and caused by Staphylococcus epidermidis. The initial management was vitreous tap and IVT injection of antibiotics followed by PPV in 6 (85.7%) cases. One (14.3%) case underwent evisceration. Visual acuity improved at last visit in only 2 (28.6%) cases. The rate of endophthalmitis was 0.0004% for bevacizumab. Conclusions: The rate of endophthalmitis after IVT bevacizumab and ranibizumab was very low. We recommend following a standardized injection protocol, adherence to sterile techniques, and proper patient follow-up are determinant factors for low incidence rates. In addition, endophthalmitis after IVT bevacizumab and ranibizumab have poor visual outcomes despite prompt treatment. PMID:26957840

  4. Analysis of nonisothermal injection and falloff tests in layered reservoirs

    SciTech Connect

    Halfman, S.E.; Benson, S.M.

    1985-03-01

    The effects of reservoir layering and gravity segregation on nonisothermal injection and falloff tests are investigated. Results show that layering does not affect injection or falloff data if all the layers are permeable and accept fluids from the wellbore. In such cases, the average permeability, skin factor, and distance to the thermal front can be calculated using the techniques developed for homogeneous reservoirs. Special considerations have to be taken for cases where several layers are impermeable or are permeable but do not accept fluids of the well face. In the first case (impermeable layers), knowledge of the total thickness of the permeable layers is required for the existing techniques to be applied successfully. In the second case, the existing techniques cannot be applied, but characteristic responses from injection and falloff test are seen; therefore, this case can be identified easily. 13 refs., 8 figs.

  5. Radiation analysis of the ITER pellet injection system

    SciTech Connect

    Gouge, M.J. ); Gomes, I.C.; Gomes, L.T.; Stevens, P.N, )

    1991-03-01

    The results of neutronics calculations for the pellet injection system of the International Thermonuclear Experimental Reactor (ITER) are described. Hands-on maintenance of components in the pellet injection room results in a considerable simplification of maintenance support equipment and in greater system availability. The basic configuration of the pellet injection system includes small-diameter guide tubes with which the pellet may have several small-angle collisions before reaching the plasma. The pellet injector port through which the guide tubes pass will be shared with ITER plasma diagnostics, so the calculation takes into account penetrations to accommodate numerous channels for a neutron spectrometer and neutron and gamma-ray cameras. The conservative assumption of steady-state operation of ITER for 1000 days was taken as the baseline for calculating the activation of components in the pellet injection room. The plasma configuration is based on the current ITER guidelines, the first wall configuration is based on the most recently updated configuration, and the blanket configuration is based on the US proposal for the blanket. The plasma, coils, and blanket regions were analyzed with the Monte Carlo code MCNP. The transport of neutrons through the penetrations was also performed with MCNP. The pellet injection room was modeled with the two-dimensional discrete ordinates code DORT, which was also used for the transport of neutrons during operation and of gamma rays caused by activation. The activation calculations were carried out with the REBATE code. Results from this study indicate that restricted personnel access to the pellet injection room is possible, so limited hands-on maintenance can be performed on the majority of the components in the room.

  6. Serum levels of intravitreal bevacizumab after vitrectomy, lensectomy and non-surgical controls

    PubMed Central

    Christoforidis, John B.; Xie, Zhiliang; Jiang, Angela; Wang, Jillian; Pratt, Cedric; Gemensky-Metzler, Anne; Abdel-Rasoul, Mahmoud; Roy, Sashwati; Liu, Zhongfa

    2013-01-01

    Purpose To determine serum level differences of intravitreally-placed bevacizumab after vitrectomy and lensectomy-vitrectomy and to compare these with non-operated eyes in a rabbit model. Methods Five Dutch-belted rabbits underwent pars plana vitrectomy (PPV), 5 rabbits underwent pars plana lensectomy (PPL) and 5 rabbits served as non-surgical controls. Twelve days following the surgical procedures, each operated eye underwent an intravitreal injection consisting of 1.25 mg/0.05 mL bevacizumab. Serum levels from each rabbit were drawn on days 2, 4, 7, 10, 14, 21, 28 and 35 and were measured with ELISA immunoassay. Results The average peak serum concentration (Cmax) was highest for the PPL group (11.33 µg ± 3.48 mL), and was similar between the PPV (5.35 µg ± 2.69 mL) and non-surgical control groups (5.35 µg ± 0.69 mL). The average time to maximal plasma concentration (Tmax) in days was earliest for the PPL group (2.8 ± 0.47), followed by the PPV (5.6 ± 0.84) and non-surgical control groups (6.4 ± 0.71). The PPL group had higher serum levels than the other 2 groups until day 7 that was significant only at day 2 (p<0.0001). After day 4 there were no significant differences or trends between any of the 3 groups. The half-life (T1/2) was fastest for the PPL group (1.41±0.21 days) followed by the PPV (2.80±3.35 days) and non-surgical control groups (6.69±10.4 days). Conclusions Serum bevacizumab levels were initially elevated following lensectomy and vitrectomy compared to non-surgical eyes following intravitreal injection. The half-life of bevacizumab was prolonged in non-surgical eyes presumably due to a slower release from the vitreous cavity. PMID:23548066

  7. Intravitreal Phacoemulsification Using Torsional Handpiece for Retained Lens Fragments

    PubMed Central

    Kumar, Vinod; Takkar, Brijesh

    2016-01-01

    Purpose: To evaluate the results of intravitreal phacoemulsification with torsional hand piece in eyes with posteriorly dislocated lens fragments. Methods: In this prospective, interventional case series, 15 eyes with retained lens fragments following phacoemulsification were included. All patients underwent standard three-port pars plana vitrectomy and intravitreal phacoemulsification using sleeveless, torsional hand piece (OZiL™, Alcon's Infiniti Vision System). Patients were followed up for a minimum of six months to evaluate the visual outcomes and complications. Results: The preoperative best-corrected visual acuity (BCVA) ranged from light perception to 0.3. No complications such as thermal burns of the scleral wound, retinal damage due to flying lens fragments, or difficult lens aspiration occurred during intravitreal phacoemulsification. Mean post-operative BCVA at the final follow-up was 0.5. Two eyes developed cystoid macular edema, which was managed medically. No retinal detachment was noted. Conclusion: Intravitreal phacoemulsification using torsional hand piece is a safe and effective alternative to conventional longitudinal phacofragmentation.

  8. QUANTITATIVE ANALYSIS OF ALKYL OF PHOSPHATES USING AUTOMATED COOL ON-COLUMN AQUEOUS INJECTION

    EPA Science Inventory

    A gas chromatographic method of analysis for trimethyl and triethyl phosphates was developed that used direct aqueous injection. utomated, cool, on-column injection was investigated because of the large number of samples to be analyzed and the realization that the best inlet syst...

  9. Separation window dependent multiple injection (SWDMI) for large scale analysis of therapeutic antibody N-glycans.

    PubMed

    Kovács, Zsuzsanna; Szarka, Máté; Szigeti, Márton; Guttman, András

    2016-09-01

    There is a growing demand in the biopharmaceutical industry for large scale N-glycosylation analysis of biotherapeutics, especially monoclonal antibodies. To fulfill this high throughput analysis requirement with single column separation systems in most instances require finishing the entire analysis cycle including conditioning, injection and separation between sample injections. While in liquid chromatography it represents a challenge, multiple sample injection in capillary electrophoresis has already been demonstrated for one or two sample components by utilizing the concept of introducing sequential sample and buffer zones into the capillary tubing before the start of the separation process. It was also demonstrated in CE-MS mode, mostly to follow one sample component, identified by precise mass measurement. Here we introduce a novel multiple injection approach for rapid large scale capillary electrophoresis analysis of samples with biopharmaceutical interest supporting multicomponent optical detection with laser induced fluorescence. In Separation Window Dependent Multiple Injection (SWDMI) mode, the samples are consecutively injected in predefined time intervals, based on the window that covers the separation of all sample components. As a practical example, this newly developed SWDMI protocol was applied to rapid and large scale analysis of APTS labeled monoclonal antibody N-glycans using a short (20cm effective length) capillary column. Full analysis of 96 samples (injected from a well plate) was obtained in 4h, in contrast to consecutive individual separation cycle processing of the same samples that required 12h. PMID:27337190

  10. Adaptive Injection-locking Oscillator Array for RF Spectrum Analysis

    SciTech Connect

    Leung, Daniel

    2011-04-19

    A highly parallel radio frequency receiver using an array of injection-locking oscillators for on-chip, rapid estimation of signal amplitudes and frequencies is considered. The oscillators are tuned to different natural frequencies, and variable gain amplifiers are used to provide negative feedback to adapt the locking band-width with the input signal to yield a combined measure of input signal amplitude and frequency detuning. To further this effort, an array of 16 two-stage differential ring oscillators and 16 Gilbert-cell mixers is designed for 40-400 MHz operation. The injection-locking oscillator array is assembled on a custom printed-circuit board. Control and calibration is achieved by on-board microcontroller.