Home About us Contact
|
Home About us Contact | ||
|
|
||
Intravitreal Injection (intravitreal + injection)
Kinds of Intravitreal Injection Selected AbstractsOcular Changes after Intravitreal Injection of Methanol, Formaldehyde, or Formate in RabbitsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2001Yoriko Hayasaka One hundred ,l of 1% methanol, 1% or 0.1% formaldehyde, or 1% formate was injected in the vitreous cavity of the right eyes of rabbits. The eyes were examined by biomicroscopy and ophthalmoscopy weekly. One month after injection, the eyes were enucleated and examined histologically. One week after treatment the animals that received 0.1% formaldehyde showed retinal vessel dilation, and the rabbits that received 1% formaldehyde showed mild posterior subcapsular cataract and retinal vessel dilation and haemorrhages. One month after treatment, the animals that received 0.1% or 1% formaldehyde developed mild posterior subcapsular cataract and retinal lesions. Animals that received 1% methanol or 1% formate showed nearly normal optical media and fundi. Histologically disorganized retina and optic nerve were seen in eyes that received 0.1% or 1% formaldehyde. Eyes that received 1% methanol or 1% formate appeared histologically normal. Our findings indicate that intravitreal injection of formaldehyde causes retinal and optic nerve damage, while methanol and formate are not or less toxic to ocular tissues. [source] Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Yvonne de Kozak Abstract In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1,2,days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17,-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class,II+ inflammatory cells and low expression of TNF-,, IL-1,, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-, production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis. [source] Evidence for the involvement of purinergic P2X7 receptors in outer retinal processingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006Theresa Puthussery Abstract Extracellular ATP mediates fast excitatory neurotransmission in many regions of the central nervous system through activation of P2X receptors. Although several P2X receptor subunits have been identified in the mammalian retina, little is known about the functional role of these receptors in retinal signalling. The purpose of the present study was to investigate whether purinergic P2X7 receptors are involved in outer retinal processing by assessing receptor localization, degradation of extracellular ATP and the effect of functional activation of P2X7 receptors on the electroretinogram (ERG). Using light and electron microscopy, we demonstrated that P2X7 receptors are expressed postsynaptically on horizontal cell processes as well as presynaptically on photoreceptor synaptic terminals in both the rat and marmoset retina. Using an enzyme cytochemical method, we showed that ecto-ATPases are active in the outer plexiform layer of the rat retina, providing a mechanism by which purinergic synaptic transmission can be rapidly terminated. Finally, we evaluated the role of P2X7 receptors in retinal function by assessing changes to the ERG response of rats after intravitreal delivery of the P2X7 receptor agonist benzoyl benzoyl ATP (BzATP). Intravitreal injection of BzATP resulted in a sustained increase (up to 58%) in the amplitude of the photoreceptor-derived a-wave of the ERG. In contrast, BzATP caused a transient reduction in the rod- and cone-derived postreceptoral responses. These results provide three lines of evidence for the involvement of extracellular purines in outer retinal processing. [source] STAT3 activation in photoreceptors by leukemia inhibitory factor is associated with protection from light damageJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Yumi Ueki Abstract Members of the interleukin-6 cytokine family, including leukemia inhibitory factor (LIF), signal through gp130. The neuroprotective role of gp130 activation has been widely demonstrated in both CNS and PNS, but the mechanism by which this is accomplished is not well established. We investigated temporal and cell-specific activation of signaling pathways induced by LIF in the mature mouse retina. Intravitreal injection of LIF preserved photoreceptor function and prevented photoreceptor cell death from light-induced oxidative damage in a dose-dependent manner (2 days post-injection). A therapeutic dose of LIF induced rapid and sustained activation of signal transducer and activator of transcription (STAT) 3. Activated STAT3 was localized to all the retinal neurons and glial cells, including photoreceptors. Activation of extracellular signal-regulated kinase 1 and 2 was robust but transient in Müller glial cells, and undetectable at the time of light exposure. Akt was not activated by LIF. We also show that at the time of neuroprotection, STAT3 but not extracellular signal-regulated kinase 1 and 2 or the Akt pathways was active in LIF-treated retinas, and activated STAT3 was clearly localized in transcriptionally active areas of photoreceptor nuclei. Our data suggest that photoreceptor protection in response to LIF can be directly mediated by activation of STAT3 in photoreceptors. [source] Feline immunodeficiency virus vectors.THE JOURNAL OF GENE MEDICINE, Issue 5 2002Gene transfer to mouse retina following intravitreal injection Abstract Background Transduction of the murine retinal pigmented epithelium (RPE) with adenovirus vectors requires technically difficult and invasive subretinal injections. This study tested the hypothesis that recombinant vectors based on feline immunodeficiency virus (FIV) could access the retina following intravitreal injection. Methods FIV vectors expressing E. coli ,-galactosidase (FIV,gal) were injected alone, or in combination with adenovirus vectors expressing eGFP, into the vitreous of normal mice and eyes evaluated for transgene expression. In further studies, the utility of FIV-mediated gene transfer to correct lysosomal storage defects in the anterior and posterior chambers of eyes was tested using recombinant FIV vectors expressing ,-glucuronidase. FIV,gluc vectors were injected into ,-glucuronidase-deficient mice, an animal model of mucopolysacharridoses type VII. Results The results of this study show that similar to adenovirus, both corneal endothelium and cells of the iris could be transduced following intravitreal injection of FIV,gal. However, in contrast to adenovirus, intravitreal injection of FIV,gal also resulted in transduction of the RPE. Immunohistochemistry following an intravitreal injection of an AdeGFP (adenovirus expressing green fluorescent protein) and FIV,gal mixture confirmed that both viruses mediated transduction of corneal endothelium and cells of the iris, while only FIV,gal transduced cells in the retina. Using the ,-glucuronidase-deficient mouse, the therapeutic efficacy of intravitreal injection of FIV,gluc (FIV expressing ,-glucuronidase) was tested. Intravitreal injection of FIV,gluc to the eyes of ,-glucuronidase-deficient mice resulted in rapid reduction (within 2,weeks) of the lysosomal storage defect within the RPE, corneal endothelium, and the non-pigmented epithelium of the ciliary process. Transgene expression and correction of the lysosomal storage defect remained for at least 12,weeks, the latest time point tested. Conclusion These studies demonstrate that intravitreal injection of FIV-based vectors can mediate efficient and lasting transduction of cells in the cornea, iris, and retina. Copyright © 2002 John Wiley & Sons, Ltd. [source] 3415: Treatment of postoperative macular edemaACTA OPHTHALMOLOGICA, Issue 2010I PETROPOULOS Purpose Cystoid macular edema (CME) is a frequent complication of a number of interventions in ophthalmology, such as cataract surgery (Irvine-Gass syndrome), laser procedures, and trabeculectomy. The purpose of this talk is to present the latest bibliographic data regarding the appropriate treatment of postoperative CME. Methods A review of the existing literature concerning the treatment of postoperative CME is performed. Characteristic personal cases are presented. Results In more than two-thirds of the cases, postoperative CME resolves spontaneously within weeks or months. Prophylactic topical treatment with indomethacin or flurbiprofen seems to reduce the frequency of clinical and angiographic CME, but its beneficial effect on final visual acuity is not established. Curative therapy includes topical corticosteroids; topical non-steroidal anti-inflammatory drugs (e.g. ketorolac); oral acetazolamide; sub-Tenon or intravitreal injection of triamcinolone acetonide; intravitreal injection of anti-VEGF drugs; and pars plana vitrectomy. The indications, role, and efficacy of each of the above treatment modalities are discussed, based on the latest bibliographic data. Conclusion Most cases of postoperative CME are mild and resolve spontaneously. In refractory cases, sub-Tenon or intravitreal injection of triamcinolone acetonide can be effective, but the risk of ocular hypertony is high. Intravitreal injection of anti-VEGF drugs offers promising results, yet large-scale randomized studies are necessary to validate their utility. Finally, pars plana vitrectomy is the treatment of choice when vitreomacular traction and/or epiretinal membrane is present. [source] 4367: Intravitreal injection of anti-VEGF and diagnosis of primary intraocular-central nervous system lymphomaACTA OPHTHALMOLOGICA, Issue 2010J GAMBRELLE Purpose We report the case of the diagnosis of primary intraocular- central nervous system (CNS) lymphoma in a patient treated by anti-VEGF. Methods An 88-year old female, with a medical history of bilateral ARMD treated by intravitreal injections of ranibizumab for 1 year, was referred to our department for bilateral vitritis diagnosed 10 days after the last anti-VEGF injection. A complete vitritis work-up including aqueous humour analysis, magnetic resonance imaging of the brain and vitreous biopsy enabled us to confirm the diagnosis of primary intraocular-CNS lymphoma. Results To the best of our knowledge, this is the first report of the diagnosis of primary intraocular-CNS lymphoma in a patient treated by anti-VEGF for ARMD. In our opinion, the occurrence of lymphoma in this case was coincidental and not due to the anti-VEGF injections. The differential diagnosis of vitritis in elderly patients is relatively large. Endophthalmitis or uveitis has been described after anti-VEGF injections. In such a situation, there is actually a risk of overlooking a diagnosis of intraocular lymphoma in the mistaken belief that the observed vitritis may be a reaction to administred anti-VEGFs. If no direct time-relationship with the anti-VEGF injections can be found, a classic vitritis work-up should be performed. Anti-VEGF treatment did not impede cytological diagnosis in our patient. Conclusion Although in some none-CNS non-Hodgkin lymphomas (NHL) systemic anti-VEGF therapy is added to chemotherapy schedules, the use of anti-VEGF did not halt the spread of the lesion within the eye in this case. It can, therefore, be presumed that local anti-VEGF therapy has no adjuvant effect in primary intraocular lymphoma. [source] The present role of corticosteroids in uveitisACTA OPHTHALMOLOGICA, Issue 2009M KHAIRALLAH Corticosteroids are the most widely used anti-inflammatory and immunosuppressant drugs in ophthalmology in general, and remain the mainstay of therapy for patients with uveitis. An infectious etiology for intraocular inflammation should be adequately excluded or appropriately covered with anti-infectious therapy before administration of corticosteroid therapy. Topical corticosteroids alone are usually effective in the management of anterior uveitis and have little activity against intermediate or posterior uveitis. Ocular adverse effects of topical steroid therapy mainly include ocular hypertension and cataract. The use of periocular steroid injections (subconjunctival, anterior or posterior subtenon, orbital floor) are important modalities in the management of anterior uveitis refractory to topical treatment and intermediate or posterior uveitis, particularly unilateral cases. Systemic corticosteroids remain the initial drug of choice for most patients with severe bilateral intermediate or posterior uveitis. Therapy is initiated with 1.0 to 2.0 mg/Kg of oral prednisone or prednisolone as a single morning dose, followed by a slow taper. Use of intravenous pulse steroid therapy is an important option in acute, severe, bilateral posterior segment inflammation. In several cases, the level of systemic steroid required to control the inflammation is too high and unacceptable. Immunosuppressive drugs as steroid-sparing agents are indicated is such cases. Intravitreal injection of triamcinolone acetonide and slow-release intraocular devices are therapeutic options that can be used in selected uveitis cases refractory to conventional therapy and biologic agents. [source] Intravitreal injection of bevacizumab for cystoid macular edema in retinitis pigmentosaACTA OPHTHALMOLOGICA, Issue 4 2007Gustavo Barreto Melo No abstract is available for this article. [source] Macular oedema in central retinal vein occlusion treated with intravitreal triamcinoloneACTA OPHTHALMOLOGICA, Issue 3 2006Christopher D. Gelston Abstract. Purpose:,To investigate the efficacy of intravitreal triamcinolone as treatment for macular oedema in central retinal vein occlusion (CRVO). Methods:,We conducted a retrospective comparative case series of nine patients with macular oedema associated with CRVO (six non-ischaemic and three ischaemic) treated with an intravitreal injection of 4 mg triamcinolone acetonide, compared with 10 control (observation) patients (six non-ischaemic and four ischaemic). Examination included visual acuity (VA) tests and complete ophthalmic examinations at baseline, 1, 2 and 6 months postoperatively. Results:,The mean baseline VA was 20/161 for CRVO treatment group patients and 20/75 for observation group patients (p = 0.15). No significant difference in VA between CRVO treatment group patients (20/99) and controls (20/282) was observed at the final 6-month visit (p = 0.33). Subgroup analysis of the non-ischaemic CRVO treatment patients compared with the non-ischaemic controls also showed no significant difference at the 6-month visit (20/59 and 20/100, respectively; p = 0.20). At 6 months, five of the six non-ischaemic treated patients had VA , 20/100, compared with five of the six non-ischaemic control patients. All patients tolerated the procedure well, but there was a significant increase in intraocular pressure by the 2-month visit (p = 0.015). Conclusions:,Intravitreal injection of triamcinolone may not be effective for treatment of macular oedema in all CRVO patients or all non-ischaemic CRVO patients. A trend towards VA improvement was noted but was not statistically significant. Although our treatment was not hindered by severe complications, there was a significant increase in IOP in the 2 months following treatment. [source] Intravitreal anti-vascular endothelial growth factor therapy with bevacizumab for tuberous sclerosis with macular oedemaACTA OPHTHALMOLOGICA, Issue 3 2010Wataru Saito Abstract. Purpose:, To describe two patients with macular oedema secondary to tuberous sclerosis complex (TSC) who were treated with intravitreal bevacizumab injection. Methods:, Interventional case reports. Bevacizumab 1.25 mg was injected into the vitreous of two patients with TSC-associated macular oedema / exudative retinal detachment. Vascular endothelial growth factor (VEGF) concentration in the vitreous fluid was measured by enzyme-linked immunosorbent assay (ELISA) in one of these patients. Results:, Patient 1: a 22-year-old woman with TSC was diagnosed as having multiple retinal hamartomas in both eyes. Eleven years later, the patient developed macular oedema with epiretinal membrane formation in the right eye. The patient underwent pars-plana vitrectomy with retinal photocoagulation for retinal tumours. VEGF concentration in the vitreous fluid was high compared to that in patients without retinal vascular diseases. Recurrent macular oedema disappeared by intravitreal injection of bevacizumab. Patient 2: a 32-year-old woman with TSC-associated retinal hamartoma, temporally showing macular exudative retinal detachment, developed neovascularization originated from the tumour. By intravitreal bevacizumab injection, the tumour size reduced markedly with regression of neovascularization. Conclusion:, These results suggest that VEGF derived from retinal hamartomas causes macular oedema associated with TSC. Intravitreal injections of bevacizumab may be a useful therapeutic option for macular oedema secondary to TSC. [source] Ocular toxicity of fluoroquinolonesCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 6 2007Andrew M Thompson FRANZCO Abstract The ocular toxicity of fluoroquinolones and the risks of their use in the treatment of ocular infection were reviewed. Systematic identification, selection, review and synthesis of published English-language studies relating to fluoroquinolone use and safety in animals and humans was conducted. Although not free of complications, fluoroquinolones are generally safe when used to treat ocular infection. Ocular toxicity appears to be dose-dependent and results from class-effects and specific fluoroquinolone structures. Phototoxicity and neurotoxicity have been reported, and toxic effects on ocular collagen may be associated with Achilles tendinopathy. Corneal precipitation may provide an advantageous drug depot but delay healing and result in corneal perforation in approximately 10% of cases. Although human toxicity studies are limited, the current recommended dose for intracameral injection of ciprofloxacin is less than 25 ,g. Intravitreal injections of ciprofloxacin 100 ,g, ofloxacin 50 ,g/mL, trovafloxacin 25 ,g or less, moxifloxacin 160 ,g/0.1 mL or less and pefloxacin 200 ,g/0.1 mL are considered safe. [source] A review of antiviral therapies in the treatment of cytomegalovirusDERMATOLOGIC THERAPY, Issue 3 2000Adrienne M. Hinkle ABSTRACT: Cytomegalovirus (CMV) is a member of the herpesvirus family that is very prevalent world wide based on serologic testing. In immunocompromised persons CMV produces high rates of morbidity and mortality. Congenital CMV is the leading infectious cause of fetal abnormalities in the United States. Infection of human immunodeficiency virus (HIV) seropositive persons or transplant patients with CMV can produce retinitis, encephalitis, pneumonitis, hepatitis, gastrointestinal ulcerations, and cutaneous lesions. Three intravenous therapies are available for CMV infections: ganciclovir; foscarnet and cidofovir. Most recently a fourth antiviral agent was approved for intravitreal injection. This drug, fomivirsen, is the first antisense oligonucleotide available for therapeutic use. A number of other antiviral drugs and vaccines are currently under study. [source] Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Yvonne de Kozak Abstract In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1,2,days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17,-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class,II+ inflammatory cells and low expression of TNF-,, IL-1,, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-, production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis. [source] Expression of glial fibrillary acidic protein and glutamine synthetase by Müller cells after optic nerve damage and intravitreal application of brain-derived neurotrophic factorGLIA, Issue 2 2002Hao Chen Abstract Müller glia play an important role in maintaining retinal homeostasis, and brain-derived neurotrophic factor (BDNF) has proven to be an effective retinal ganglion cell (RGC) neuroprotectant following optic nerve injury. The goal of these studies was to investigate the relation between optic nerve injury and Müller cell activation, and to determine the extent to which BDNF affects the injury response of Müller cells. Using immunocytochemistry and Western blot analysis, temporal changes in the expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) were examined in rats after optic nerve crush alone, or in conjunction with an intravitreal injection of BDNF (5 ,g). GFAP protein levels were normal at 1 day post-crush, but increased ,9-fold by day 3 and remained elevated over the 2-week period studied. Müller cell GS expression remained stable after optic nerve crush, but the protein showed a transient shift in its cellular distribution; during the initial 24-h period post-crush the GS protein appeared to translocate from the cell body to the inner and outer glial processes, and particularly to the basal endfeet located in the ganglion cell layer. BDNF alone, or in combination with optic nerve crush, did not have a significant effect on the expression of either GFAP or GS compared with the normal retina, or after optic nerve crush alone, respectively. The data indicate that although BDNF is a potent neuroprotectant in the vertebrate retina, it does not appear to have a significant influence on Müller cell expression of either GS or GFAP in response to optic nerve injury. GLIA 38:115,125, 2002. © 2002 Wiley-Liss, Inc. [source] Adenosine A2a receptor-mediated inhibition of rod opsin mRNA expression in tiger salamanderJOURNAL OF NEUROCHEMISTRY, Issue 3 2002Peter D. Alfinito Abstract The neuromodulator adenosine mediates dark-adaptive changes in retinal photoreceptors through A2a receptors. In cold-blooded vertebrates, opsin mRNA expression is lower at night than during the day. In the present study, we tested whether adenosine could inhibit opsin mRNA expression in cultured rod cells and if endogenous adenosine acts to suppress opsin mRNA in the intact retina at night. Semi-quantitative in situ hybridization showed that treatment with 100 nm of the A2a/A2b agonist N,6 -[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) reduced opsin mRNA 41% in cultured rod cells. The effect of DPMA was blocked by 10 µm of the A2a antagonist 8-(3-chlorostyryl)caffeine (CSC) but not by 10 µm of the A2b antagonist alloxazine. One micromolar adenosine alone had no effect on opsin mRNA. However, in the presence of the adenosine deaminase inhibitor erythro -9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA), 1 µm adenosine reduced opsin mRNA 61%. EHNA alone reduced opsin mRNA by 26%. Consistent with an A2a receptor mechanism, 100 nm forskolin (adenylate cyclase agonist) decreased opsin mRNA 34%. Finally, northern blots showed that intravitreal injection of 10 µm CSC at night increased opsin I mRNA 38%. Thus, endogenous adenosine suppresses rod opsin I mRNA expression at night; in vitro results indicate this reduction occurs through A2a -like receptor binding and stimulation of adenylate cyclase activity. [source] Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye dropsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2007Thorsteinn Loftsson Delivery of steroids to the retina is currently undertaken with invasive injections into the vitreous cavity. This paper describes a non-invasive method to deliver steroids in therapeutic levels to the retina in rabbits. Dexamethasone was formulated as somewhat water-soluble dexamethasone/,-cyclodextrin (,CD) microparticles in a low-viscosity aqueous eye drop suspension. The mean (± standard deviation) diameter of the particles was 20.4 ± 10.3 ,m, with no particles larger than 60 ,m. The aqueous suspension formulation was tested in rabbits and compared with an aqueous dexamethasone eye drop solution containing randomly methylated ,-cyclodextrin (RM,CD). The dexamethasone concentration was identical in both formulations (15 mg mL,1). The drug was administered to the left eye but determined in both eyes. The amount reaching different eye tissues via the topical route was determined by subtracting the amount found in the right eye from the amount found in the left eye. Two hours after single application of the dexamethasone/,CD eye drops to rabbits the mean (± s.d.) concentration in vitreous was 29 ± 16 ng g,1, 86% of which reached vitreous via the topical route and in retina the concentration was 57 ± 22 ng g,1 (49% via topical route). For the RM,CD the values were 22.6 ± 9 and 66 ± 49 ng g,1 (73 and 14% via topical route), respectively. These steroid levels are comparable with the dexamethasone concentration achieved 1 month after intravitreal injection. The aqueous dexamethasone/,CD eye drop formulation was chemically stable during 7 months storage and well tolerated with no visible short-term side effects. [source] Sustained ocular delivery of tilisolol to rabbits after topical administration or intravitreal injection of lipophilic prodrug incorporated in liposomesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2001Shigeru Kawakami To improve the retention time of tilisolol in the precorneal area or vitreous body, we prepared liposomes incorporating the O -palmitoyl prodrug of tilisolol. O -Palmitoyl tilisolol was completely incorporated in the liposomes. After topical administration of O -palmitoyl tilisolol liposomes to the rabbit eye, O -palmitoyl tilisolol rapidly disappeared from the tear fluid. The inclusion of 2% carmellose sodium slightly prolonged the retention of O -palmitoyl tilisolol in the tear fluid. After intravitreal injection of O -palmitoyl tilisolol liposomes, there was a relatively prolonged retention of O -palmitoyl tilisolol in the vitreous body. At 24 and 48 h after intravitreal injection of O -palmitoyl tilisolol liposomes, the tilisolol concentration in the vitreous body was significantly higher compared with the concentration after intravitreal injection of tilisolol liposomes. [source] MRI in ocular drug deliveryNMR IN BIOMEDICINE, Issue 9 2008S. Kevin Li Abstract Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Feline immunodeficiency virus vectors.THE JOURNAL OF GENE MEDICINE, Issue 5 2002Gene transfer to mouse retina following intravitreal injection Abstract Background Transduction of the murine retinal pigmented epithelium (RPE) with adenovirus vectors requires technically difficult and invasive subretinal injections. This study tested the hypothesis that recombinant vectors based on feline immunodeficiency virus (FIV) could access the retina following intravitreal injection. Methods FIV vectors expressing E. coli ,-galactosidase (FIV,gal) were injected alone, or in combination with adenovirus vectors expressing eGFP, into the vitreous of normal mice and eyes evaluated for transgene expression. In further studies, the utility of FIV-mediated gene transfer to correct lysosomal storage defects in the anterior and posterior chambers of eyes was tested using recombinant FIV vectors expressing ,-glucuronidase. FIV,gluc vectors were injected into ,-glucuronidase-deficient mice, an animal model of mucopolysacharridoses type VII. Results The results of this study show that similar to adenovirus, both corneal endothelium and cells of the iris could be transduced following intravitreal injection of FIV,gal. However, in contrast to adenovirus, intravitreal injection of FIV,gal also resulted in transduction of the RPE. Immunohistochemistry following an intravitreal injection of an AdeGFP (adenovirus expressing green fluorescent protein) and FIV,gal mixture confirmed that both viruses mediated transduction of corneal endothelium and cells of the iris, while only FIV,gal transduced cells in the retina. Using the ,-glucuronidase-deficient mouse, the therapeutic efficacy of intravitreal injection of FIV,gluc (FIV expressing ,-glucuronidase) was tested. Intravitreal injection of FIV,gluc to the eyes of ,-glucuronidase-deficient mice resulted in rapid reduction (within 2,weeks) of the lysosomal storage defect within the RPE, corneal endothelium, and the non-pigmented epithelium of the ciliary process. Transgene expression and correction of the lysosomal storage defect remained for at least 12,weeks, the latest time point tested. Conclusion These studies demonstrate that intravitreal injection of FIV-based vectors can mediate efficient and lasting transduction of cells in the cornea, iris, and retina. Copyright © 2002 John Wiley & Sons, Ltd. [source] Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogramTHE JOURNAL OF PHYSIOLOGY, Issue 10 2008Deb Kumar Mojumder Voltage-gated sodium channels (Nav channels) in retinal neurons are known to contribute to the mammalian flash electroretinogram (ERG) via activity of third-order retinal neurons, i.e. amacrine and ganglion cells. This study investigated the effects of tetrodotoxin (TTX) blockade of Nav channels on the b-wave, an ERG wave that originates mainly from activity of second-order retinal neurons. ERGs were recorded from anaesthetized Brown Norway rats in response to brief full-field flashes presented over a range of stimulus energies, under dark-adapted conditions and in the presence of steady mesopic and photopic backgrounds. Recordings were made before and after intravitreal injection of TTX (,3 ,m) alone, 3,6 weeks after optic nerve transection (ONTx) to induce ganglion cell degeneration, or in combination with an ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 200 ,m) to block light-evoked activity of inner retinal, horizontal and OFF bipolar cells, or with the glutamate agonist N -methyl- d -aspartate (NMDA, 100,200 ,m) to reduce light-evoked inner retinal activity. TTX reduced ERG amplitudes measured at fixed times corresponding to b-wave time to peak. Effects of TTX were seen under all background conditions, but were greatest for mesopic backgrounds. In dark-adapted retina, b-wave amplitudes were reduced only when very low stimulus energies affecting the inner retina, or very high stimulus energies were used. Loss of ganglion cells following ONTx did not affect b-wave amplitudes, and injection of TTX in eyes with ONTx reduced b-wave amplitudes by the same amount for each background condition as occurred when ganglion cells were intact, thereby eliminating a ganglion cell role in the TTX effects. Isolation of cone-driven responses by presenting test flashes after cessation of a rod-saturating conditioning flash indicated that the TTX effects were primarily on cone circuits contributing to the mixed rod,cone ERG. NMDA significantly reduced only the additional effects of TTX on the mixed rod,cone ERG observed under mesopic conditions, implicating inner retinal involvement in those effects. After pharmacological blockade with CNQX, TTX still reduced b-wave amplitudes in cone-isolated ERGs indicating Nav channels in ON cone bipolar cells themselves augment b-wave amplitude and sensitivity. This augmentation was largest under dark-adapted conditions, and decreased with increasing background illumination, indicating effects of background illumination on Nav channel function. These findings indicate that activation of Nav channels in ON cone bipolar cells affects the b-wave of the rat ERG and must be considered when analysing results of ERG studies of retinal function. [source] Ocular Changes after Intravitreal Injection of Methanol, Formaldehyde, or Formate in RabbitsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2001Yoriko Hayasaka One hundred ,l of 1% methanol, 1% or 0.1% formaldehyde, or 1% formate was injected in the vitreous cavity of the right eyes of rabbits. The eyes were examined by biomicroscopy and ophthalmoscopy weekly. One month after injection, the eyes were enucleated and examined histologically. One week after treatment the animals that received 0.1% formaldehyde showed retinal vessel dilation, and the rabbits that received 1% formaldehyde showed mild posterior subcapsular cataract and retinal vessel dilation and haemorrhages. One month after treatment, the animals that received 0.1% or 1% formaldehyde developed mild posterior subcapsular cataract and retinal lesions. Animals that received 1% methanol or 1% formate showed nearly normal optical media and fundi. Histologically disorganized retina and optic nerve were seen in eyes that received 0.1% or 1% formaldehyde. Eyes that received 1% methanol or 1% formate appeared histologically normal. Our findings indicate that intravitreal injection of formaldehyde causes retinal and optic nerve damage, while methanol and formate are not or less toxic to ocular tissues. [source] Effect of caffeic acid phenethyl ester on treatment of experimentally induced methicillin-resi,stant Staphylococcus epidermidis endophthalmitis in a rabbit modelCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2007Özlem Y Abstract This study investigated the anti-inflammatory effects of caffeic acid phenethyl ester (CAPE), a natural bee-produced compound, and compared it with corticosteroids in the treatment of experimentally induced methicillin-resistant Staphylococcus epidermidis (MRSE) endophthalmitis in addition to intravitreal antibiotics. An experimental endophthalmitis model was produced in 24 New Zealand albino rabbits by unilateral intravitreal injection of 0.1,ml of 4.7,×,104 colony-forming units (CFU) methicillin-resistant S. epidermidis. The animals were then divided randomly into three treatment groups and a control group, group 1 (six rabbits), received only intravitreal vancomycin (1.0,mg/0.1,ml); group 2 (six rabbits), received both intravitreal vancomycin (1.0,mg/0.1,ml) and intravitreal dexamethasone (400,µg/0.1,ml) and group 3 (six rabbits), received both intravitreal vancomycin (1.0,mg/0.1,ml) and subtenon CAPE (10,mg/0.3,ml) after 24,h post-infection. No treatment was given to the control group. Treatment efficacy was assessed by clinical examination, vitreous culture and histopathology. There were no statististically significant differences between clinical scores of all groups in examinations at 24 and 48,h post-infection (p,=,0.915 and p,=,0.067 respectively), but in examinations at 72,h post-infection and after 7 days post-infection, although the clinical scores of treatment groups were not significantly different from each other, they were significantly lower than the control group (p,<,0.05). The culture results of all groups were sterile. As a result, CAPE was found to be as effective as dexamethasone in reducing inflammation in the treatment of experimental MRSE endophthalmitis when used with antibiotics. More studies are needed to determine the optimal administration route and effective dosage of this compound. Copyright © 2006 John Wiley & Sons, Ltd. [source] Combined intravitreal bevacizumab and triamcinolone in exudative age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 6 2010Jost B. Jonas Acta Ophthalmol. 2010: 88: 630,634 Abstract. Purpose:, We report on the combined application of intravitreal bevacizumab and triamcinolone acetonide for treatment of exudative age-related macular degeneration (AMD). Methods:, The clinical interventional case-series study included 16 patients (16 eyes) with exudative AMD who had previously received 3.5 ± 1.8 mono-injections of bevacizumab (1.5 mg) without significant improvement in visual acuity (VA) or reduction in macular exudation. All patients underwent a combined intravitreal injection of bevacizumab (1.5 mg) and triamcinolone acetonide (about 20 mg). Main outcome measures were VA and macular thickness as determined by optical coherence tomography. All patients were re-examined at 2,3 months after the intervention. Results:, Visual acuity improved significantly (p = 0.03) from 0.80 ± 0.40 logMAR prior to the combined injection to 0.65 ± 0.42 logMAR at 3 months after the injection. An improvement of , 1 Snellen line was found in eight subjects, an increase of , 2 lines in five subjects, and an improvement of , 3 lines in two subjects. One patient lost 1 line and one patient lost 3 lines. Central retinal thickness decreased significantly from 272 ± 62 ,m to 220 ± 47 ,m (p = 0.03). At the 6-month follow-up examination, central retinal thickness had increased again to 319 ± 142 ,m, which was not significantly (p = 0.30) different from baseline measurements. Conclusions:, The combined intravitreal application of bevacizumab and triamcinolone may temporarily be helpful in the treatment of exudative AMD if previous intravitreal bevacizumab mono-injections have failed to improve vision and reduce macular oedema. [source] Reducing the incidence of early postoperative vitreous haemorrhage by preoperative intravitreal bevacizumab in vitrectomy for diabetic tractional retinal detachmentACTA OPHTHALMOLOGICA, Issue 6 2010Ling Yeung Acta Ophthalmol. 2010: 88: 635,640 Abstract. Purpose:, This study aimed to evaluate whether preoperative intravitreal injection of bevacizumab reduces early postoperative vitreous haemorrhage (VH) in vitrectomy for diabetic tractional retinal detachment. Methods:, We conducted a retrospective chart review of a consecutive, interventional case series. This included 29 eyes (27 patients) in the bevacizumab group and 40 eyes (37 patients) in the non-bevacizumab group. For statistical analysis, each patient was assigned to one of four groups according to the haemostatic modalities used (group 1, none; group 2, only long-acting gas; group 3, only preoperative intravitreal bevacizumab; group 4, both long-acting gas and preoperative intravitreal bevacizumab). The primary outcome measure was the incidence of early postoperative VH. The secondary outcome measure was visual acuity (VA) at 1 month. Results:, The incidence of early postoperative VH was highest in group 1 (63%), followed by group 2 (21%), group 3 (20%) and group 4 (5%). Group 3 showed the best visual recovery in the first month. All eyes in group 3 reached VA , 1/100 at 1 month after the operation, compared with 44%, 29% and 42% in groups 1, 2 and 4, respectively. Conclusions:, Preoperative intravitreal injection of bevacizumab may be useful for reducing early postoperative VH in vitrectomy for diabetic tractional retinal detachment. Eyes receiving preoperative intravitreal bevacizumab without the use of long-acting gas achieved the best visual recovery at 1 month after the operation. [source] Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin®) in neovascular age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 6 2010Philippe Bonnin Acta Ophthalmol. 2010: 88: 641,645 Abstract. Purpose:, Angiogenic inhibitors, alone or combined with other therapies, are believed to represent a promising treatment for neovascularization in age-related macular degeneration (wet AMD). They can maintain or improve visual acuity (VA), at least for the first 2 years. However, evolution to retinal atrophy cannot be ruled out and it may be useful to assess the effects of antiangiogenic therapy on retinal and choroidal circulation. Methods:, We carried out a pilot study in 15 patients with wet AMD. Time-averaged mean blood flow velocities (BFVs) in the central retinal, temporal posterior ciliary and ophthalmic arteries (CRA, TPCA and OA) were measured by ultrasound imaging before and 4 weeks after a single intravitreal injection of 1.25 mg bevacizumab in 0.05 ml. Patients underwent two ophthalmic examinations, before and 4 weeks after injection, including VA measurement and optical coherence tomography (OCT3) examination. Results:, In treated eyes, bevacizumab injection was followed by a significant improvement in VA (from 20/125 to 20/80; p = 0.0214), and a decrease in mean central macular thickness (from 392 ± 96 ,m to 271 ± 50 ,m; p = 0.0038). Mean BFV decreased by 10% in the CRA (p = 0.0226), 20% in the TPCA (p = 0.0026) and 20% in the OA (p = 0.0003). No effect was observed in fellow eyes. Conclusions:, Intravitreal bevacizumab acutely improved VA and reduced central macular thickness in wet AMD. Ultrasound imaging revealed that BFVs decreased in all retrobulbar arteries, suggesting that after local diffusion, bevacizumab exerts a short-term regional effect. Bevacizumab might therefore induce hypoperfusion of the whole eye, which may correspond to a vascular side-effect. [source] The role of CTGF in the diabetic rat retina and its relationship with VEGF and TGF-,2, elucidated by treatment with CTGFsiRNAACTA OPHTHALMOLOGICA, Issue 6 2010Hongwei Yang Acta Ophthalmol. 2010: 88: 652,659 Abstract. Purpose:, The critical association of connective tissue growth factor (CTGF) with diabetic retinopathy (DR) remains to be clarified. We detected alterations in the gene and protein expression of CTGF and related cytokines, including vascular endothelial growth factor (VEGF) and transforming growth factor-,2 (TGF-,2), and their response to small interfering RNA (siRNA) targeting the CTGF (CTGFsiRNA) in the retina of diabetic rats. The relationships between CTGF, VEGF and TGF-,2 levels, as well as the degree of apoptosis in the diabetic retina, were also investigated. Methods:, Diabetes was induced in rats by the ,-cell toxin streptozotocin (STZ). Retinas were obtained from control and diabetic rats and similar animals treated with CTGFsiRNA by intravitreal injection. mRNA level and protein expression of CTGF, VEGF and TGF-,2 were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, and located by immunohistochemistry. Retinal apoptosis was detected by TUNEL staining. Results:, The levels of CTGF, VEGF and TGF-,2 and the number of TUNEL-positive nuclei were significantly higher in diabetic retinas than in control retinas (p < 0.01). The level of CTGF rose at 8 weeks, earlier than levels of VEGF and TGF-,2, which rose at 12 weeks after the onset of diabetes. The difference was significant (p < 0.05). siRNA-mediated inhibition of CTGF mRNA inhibited retinal VEGF and TGF-,2 and also resulted in a significant decrease in apoptosis. Significant correlations were found between CTGF and VEGF (p = 0.009), CTGF and TGF-,2 (p = 0.01), and apoptosis and these three cytokines (p < 0.01) in the rat retina early in diabetes. Conclusions:, These results suggest that the diabetes-mediated increase in CTGF upregulates VEGF and TGF-,2 expression and induces apoptosis in the retina. This elevation may be inhibited by treatment with CTGFsiRNA. Connective tissue growth factor may serve as a potential target for the prevention and treatment of DR. [source] 2222: Hydrogen sulphide: a new CNS mediatorACTA OPHTHALMOLOGICA, Issue 2010N OSBORNE The recent discovery that hydrogen sulphide (H2S) is an endogenously produced gaseous secondary messenger capable of modulating many physiological processes, much like nitric oxide, prompted us to investigate the potential role of H2S as a retinal neuroprotective agent. In the current study we use dithiolethiones (kindly provided by Dr. Piero Del Soldato, Milan, Italy) as H2S donors and show that such substances attenuate the effect of retinal ischemia as well as oxidative and light-induced injury to a transformed line of cells (RGC-5 cells) in culture. Ischemia was delivered to rats by elevation of the intraocular pressure above the systolic blood pressure. Partial damage to the retina after seven days was determined by a combination of procedures which included analysis of electroretinograms, immunohistochemistry and changes in the retinal content of proteins and mRNAs known to be associated with ganglion cell function and apoptosis. Most of the changes caused by ischemia were significantly attenuated by intravitreal injection of a H2S donor directly after ischemia. Both light (400-700nm, intensity 1000 lux) and hydrogen peroxide caused death to RGC-5 cells in culture over a period of 24-48 hours in a time and dose-dependent manner, respectively. Light and hydrogen peroxide-induced RGC-5 cell death is by different forms of apoptosis but they are both attenuated by the H2S donor, ACS1. These initial findings demonstrate that donors of H2S may be value in the treatment of various retinal dysfunctions where oxidative stress, light or ischemia is implicated as causative fact [source] 3415: Treatment of postoperative macular edemaACTA OPHTHALMOLOGICA, Issue 2010I PETROPOULOS Purpose Cystoid macular edema (CME) is a frequent complication of a number of interventions in ophthalmology, such as cataract surgery (Irvine-Gass syndrome), laser procedures, and trabeculectomy. The purpose of this talk is to present the latest bibliographic data regarding the appropriate treatment of postoperative CME. Methods A review of the existing literature concerning the treatment of postoperative CME is performed. Characteristic personal cases are presented. Results In more than two-thirds of the cases, postoperative CME resolves spontaneously within weeks or months. Prophylactic topical treatment with indomethacin or flurbiprofen seems to reduce the frequency of clinical and angiographic CME, but its beneficial effect on final visual acuity is not established. Curative therapy includes topical corticosteroids; topical non-steroidal anti-inflammatory drugs (e.g. ketorolac); oral acetazolamide; sub-Tenon or intravitreal injection of triamcinolone acetonide; intravitreal injection of anti-VEGF drugs; and pars plana vitrectomy. The indications, role, and efficacy of each of the above treatment modalities are discussed, based on the latest bibliographic data. Conclusion Most cases of postoperative CME are mild and resolve spontaneously. In refractory cases, sub-Tenon or intravitreal injection of triamcinolone acetonide can be effective, but the risk of ocular hypertony is high. Intravitreal injection of anti-VEGF drugs offers promising results, yet large-scale randomized studies are necessary to validate their utility. Finally, pars plana vitrectomy is the treatment of choice when vitreomacular traction and/or epiretinal membrane is present. [source] 3416: Surgical therapy of macular edemaACTA OPHTHALMOLOGICA, Issue 2010CJ POURNARAS Purpose Persistent macular oedema (ME) is the main cause of poor visual outcome during the evolution of retinal ischemic microangiopathies and traction related macular distortion. Among multiples treatment approaches, vitreoretinal surgery is applied with the goal to achieve the release of a traction related component of macular oedema . Methods Vitrectomy with peeling of the posterior hyaloid, epiretinal membranes, vitreoretinal tractions and/or internal limiting membrane removal, were studied in numerous nonrandomized cases series. Results Pars plana vitrectomy has been shown to reduce macular oedema with significant change in best corrected visual acuity, in epiretinal membranes, vitreoretinal traction syndrome and ischemic microangiopathies related macular thickening central, hemiretinal, branch retinal vein occlusion and diabetic macular edema). Evidence to date does not support any therapeutic benefit from radial optic neurotomy and arteriovenous crossing sheathotomy for BRVO and CRVO related macular oedema. Conclusion In the era of intravitreal injection of steroids and anti VEGF substances, vitrectomy seems to have a beneficial effect in traction related, selected pathologies associated to chronic macular edema. [source] | |||||||||||||