A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits

Kamei, Motohiro; Misono, Kinio; Lewis, Hilel

doi:10.1016/s0002-9394(99)00239-1

Cited by 147 publications

(96 citation statements)

References 19 publications

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“…It has been reported that rTPA has retinal toxicity 18 and does not cross the intact rabbit retina. 19 Several reports have shown that pneumatic displacement therapy for SMH is equally effective with and without the use of rTPA. 9,20 Our recent report showed no significant therapeutic difference between an anti-VEGF monotherapy group and anti-VEGF combined with pneumatic displacement group.…”

Section: Discussionmentioning

confidence: 99%

Intravitreal anti-vascular endothelial growth factor monotherapy for large submacular hemorrhage secondary to neovascular age-related macular degeneration

Kim

Cho

Yoo

et al. 2015

Eye

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Section: Discussionmentioning

confidence: 99%

Intravitreal anti-vascular endothelial growth factor monotherapy for large submacular hemorrhage secondary to neovascular age-related macular degeneration

Kim

Cho

Yoo

et al. 2015

Eye

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“…[16][17][18][19] Additionally, experimental studies have shown conflicting results as to whether t-PA injected intravitreally can access the subretinal space in sufficient quantities to liquefy submacular blood clots. [20][21][22] Furthermore, Ohji et al 23 have reported success in pneumatic displacement of subretinal haemorrhage with intravitreal injection of gas alone, without t-PA. The conflicting results and potential toxicity of the technique have raised the question of whether adjunctive intravitreal injection of t-PA is in fact safe and superior to gas alone in the management of submacular haemorrhage.…”

Section: Introductionmentioning

confidence: 99%

Effects of intravitreal gas with or without tissue plasminogen activator on submacular haemorrhage in age-related macular degeneration

et al. 2007

Eye

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Purpose To compare the anatomic and functional outcomes of treating thick submacular haemorrhage with intravitreal gas injection with and without tissue plasminogen activator (t-PA) in patients with age-related macular degeneration. Methods A review of age-related macular degeneration patients with submacular haemorrhage who underwent intravitreal gas injection with and without t-PA at a tertiary referral centre was conducted. Main outcome measures were best and final postoperative visual acuity. Results A total of 53 eyes of 53 patients were included, 28 eyes received intravitreal t-PA and gas injection (t-PA and gas group) and 25 eyes received intravitreal gas injection alone (gas-alone group). Incidence of best visual acuity improvement was significantly higher in the t-PA and gas group than in the gas-alone group (60.7 vs 32.0%; P ¼ 0.037). However, subgroup analysis demonstrated that the difference was significant only in eyes with haemorrhage duration of more than 14 days (46.2 vs 8.3%; P ¼ 0.035). Incidence of final visual acuity improvement was not significantly different between the two groups (42.9 vs 28.0%; P ¼ 0.39). The complications of vitreous haemorrhage and endophthalmitis were similar between the two groups. Multiple logistic regression analysis demonstrated that shorter haemorrhage duration (o14 days) was the main factor predictive of best visual acuity improvement (OR ¼ 9.02, P ¼ 0.015). Whether t-PA was used was of borderline significance (OR ¼ 4.96, P ¼ 0.046). AbstractConclusions Intravitreal t-PA was valuable for submacular haemorrhage only in eyes with relatively old haemorrhage. For eyes with recent onset of haemorrhage, t-PA is suggested only if initial gas injection failed to displace submacular haemorrhage.

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“…This barrier restricts the permeation of large and hydrophilic molecules. In addition, there is some evidence that neural retina is also a diffusional barrier for macromolecules, [1][2][3] but the barrier properties of neural retina in terms of permeant size and charge are not known. The neural retina is a multilayer consisting of various cell types.…”

Section: Introductionmentioning

confidence: 99%

Neural retina limits the nonviral gene transfer to retinal pigment epithelium in an in vitro bovine eye model

Pitkänen

Pelkonen

Ruponen

et al. 2004

AAPS J

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We investigated the permeation of liposomal and polymeric gene delivery systems through neural retina into retinal pigment epithelium (RPE) and determined the roles of various factors in permeation and subsequent uptake of the delivery systems by RPE. Anterior parts and vitreous of fresh bovine eyes were removed. Retina was left intact or peeled away. Complexes of ethidium monoazide (EMA)-labeled plasmid DNA and cationic carriers (polyethyleneimine, poly-Llysine, DOTAP liposomes) were pipetted on the retina or RPE. Two hours later the neural retina was removed, if present, and the RPE cells were detached. Contaminants were removed by sucrose centrifugation, and the RPE cells were analyzed for DNA uptake by flow cytometry. Cellular uptake of FITC-dextrans (molecular weight [mw] 20 000, 500 000 and 2 000 000), FITC-poly-L-lysine (mw 20 000), FITClabeled oligonucleotide (15-mer), and naked EMA-labeled plasmid DNA was determined after pipetting the solutions on the RPE or neural retina. Location of the fluorescent materials in the retina was visualized with fluorescence microscopy. Neural retina decreased the cellular uptake of DNA complexes by an order of magnitude, the uptake of FITC-dextrans slightly, whereas delivery of polycationic FITC-poly-L-lysine to RPE was almost completely inhibited. Neural retina decreased the cellular uptake of FITColigonucleotides, while the uptake of uncomplexed plasmid was always negligible. Conclusions from FACS and fluorescence microscopy were similar: delivery of polymeric and liposomal DNA complexes into RPE are limited by the neural retina. This is due to the size and positive charge of the complexes.

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A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits

Cited by 147 publications

References 19 publications

Intravitreal anti-vascular endothelial growth factor monotherapy for large submacular hemorrhage secondary to neovascular age-related macular degeneration

Intravitreal anti-vascular endothelial growth factor monotherapy for large submacular hemorrhage secondary to neovascular age-related macular degeneration

Effects of intravitreal gas with or without tissue plasminogen activator on submacular haemorrhage in age-related macular degeneration

Neural retina limits the nonviral gene transfer to retinal pigment epithelium in an in vitro bovine eye model

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