tPA Injection Research Articles

Intravitreal Tissue Plasminogen Activator and Pneumatic Displacement of Submacular Hemorrhage Secondary to Retinal Artery Macroaneurysm

To assess the efficacy of treating submacular hemorrhages secondary to retinal arterial macroaneurysm with intravitreous tissue plasminogen activator (tPA) and gas. Six consecutive patients (6 eyes) with submacular hemorrhage secondary to retinal arterial macroaneurysm were included in this study. Tissue plasminogen activator, at a dose of 50 microg/0.1 mL, was injected through the pars plana into the vitreous cavity. Gas (0.3-0.5 mL of perfluoropropane) instillation followed tPA injection, either immediately after injection or sometime during the next day. Best postoperative visual acuity improved in 5 of 6 eyes (83%) and was unchanged in 1 of 6 (17%) eyes. In 5 of 6 (83%) eyes, the procedure resulted in complete or partial displacement of submacular hemorrhage out of the foveal area. Intravitreous injection of tPA and gas, followed by prone positioning of the patient, is an effective and simple treatment of submacular hemorrhage secondary to retinal arterial macroaneurysm. No complication occurred in this series.

Retinal Toxicity of Commercial Tissue Plasminogen Activator Is Mediated by the Induction of Nitric Oxide in the Mouse Retinal Primary Cells

Purpose: Tissue plasminogen activator (tPA) is an efficient thrombolytic agent, but the dose-dependent retinal toxicity of intravitreal injection of commercial tPA (containing l-arginine) has been reported. Here, we sought to investigate the mechanism of tPA-induced cell death in mouse retinal cell cultures and the role of nitric oxide (NO). Methods: Primary retinal cell cultures were maintained using glial conditioned medium (GCM) solution. Mouse retinal cell death was observed by using Hoechst-propidium iodide staining. Mouse retinal cell death was also measured by lactate dehydrogenase (LDH) assay. The formation of NO was measured using Griess reagent. Results: tPA-induced cell death was detected in mouse retinal cell cultures by Hoechst-propidium iodide staining or LDH assay. l-Arginine seems to be the major factor in retinal toxicity of commercial tPA (containing l-arginine). The formation of NO was markedly increased in mouse retinal cell cultures treated with tPA (containing l-arginine) or l-arginine. NO inhibitor reduced the cell death induced by commercially available tPA or l-arginine. Conclusions: This study suggests that l-arginine from commercial tPA (containing l-arginine) induces the majority of cell death in mouse retinal cell cultures and that its cytotoxicity may depend on the induction of NO.

Antinociceptive Properties of Mixture of α-Amyrin and β-Amyrin Triterpenes: Evidence for Participation of Protein Kinase C and Protein Kinase A Pathways

The mixture of the two pentacyclic triterpenes alpha-amyrin and beta-amyrin, isolated from the resin of Protium kleinii and given by intraperitoneal (i.p.) or oral (p.o.) routes, caused dose-related and significant antinociception against the visceral pain in mice produced by i.p. injection of acetic acid. Moreover, i.p., p.o., intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of alpha,beta-amyrin inhibited both neurogenic and inflammatory phases of the overt nociception caused by intraplantar (i.pl.) injection of formalin. Likewise, alpha,beta-amyrin given by i.p., p.o., i.t., or i.c.v. routes inhibits the neurogenic nociception induced by capsaicin. Moreover, i.p. treatment with alpha,beta-amyrin was able to reduce the nociception produced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesia caused by glutamate. On the other hand, in contrast to morphine, alpha,beta-amyrin failed to cause analgesia in thermal models of pain. The antinociception caused by the mixture of compounds seems to involve mechanisms independent of opioid, alpha-adrenergic, serotoninergic, and nitrergic system mediation, since it was not affected by naloxone, prazosin, yohimbine, DL-p-chlorophenylalanine methyl ester, or L-arginine. Interestingly, the i.p. administration of alpha,beta-amyrin reduced the mechanical hyperalgesia produced by i.pl. injection of carrageenan, capsaicin, bradykinin, substance P, prostaglandin E2, 8-Br-cAMP, and TPA in rats. However, the mixture of compounds failed to alter the binding sites of [3H]bradykinin, [3H]resiniferatoxin, or [3H]glutamate in vitro. It is concluded that the mixture of triterpene alpha-amyrin and beta-amyrin produced consistent peripheral, spinal, and supraspinal antinociception in rodents, especially when assessed in inflammatory models of pain. The mechanisms involved in their action are not completely understood but seem to involve the inhibition of protein kinase A- and protein kinase C-sensitive pathways.

Results of intravitreal tissue plasminogen activator and expansile gas injection for submacular haemorrhage in Thais

To study the results of intravitreal tissue plasminogen activator (tPA) and expansile gas injection for submacular haemorrhage in Thai patients. The medical records of Thai patients who presented with submacular haemorrhage between January 1998 and December 2002 were reviewed. The inclusion criteria were acute onset of bleeding (<1 month), treatment with intravitreal injection of tPA solution (50-100 mug in 0.1 ml) and expansile gas (0.3-0.4 ml of 100% perfluoropropane or sulphur hexafluoride), and at least 6 months of follow-up. Our main outcome measures were best final postoperative visual acuity and surgical complications. A total of 19 eyes of 19 patients completed the inclusion criteria with a mean duration of 13.1 days. The causes of haemorrhage were age-related macular degeneration in 15 eyes (78.9%), idiopathic choroidal neovascularization in two eyes (10.5%), and traumatic, and valsalva retinopathy in one eye each (5.2%). After a mean follow-up of 13 months (range 6-39 months), postoperative visual acuity improved two lines or greater in 12 eyes (63.2%), stabilized in six eyes (31.6%) and worsened in one (5.2%). The final visual acuity measured 20/63 or better in 10 eyes (52.6%). The surgical complications were breakthrough vitreous haemorrhage (three eyes) and cataracts (three eyes), and two had retinal detachments. The treatment of submacular haemorrhage with intravitreal injection of tPA and expansile gas improved visual acuity in more than half of the patients. In all, 10 in 19 eyes demonstrated final visual acuity at a functional level.

Management of macular edema in branch retinal vein occlusion with sheathotomy and recombinant tissue plasminogen activator.

The common adventitial sheath that surrounds the retinal venule and arteriole at the crossing site plays a crucial role in branch retinal vein occlusion (BRVO). The purpose of this study was to report the surgical recanalization of the occluded vein using a bimanual technique and recombinant tissue plasminogen activator (tPA) and its effect on final visual acuity. Arteriovenous sheathotomy was performed, using a bimanual technique, followed by fluid-air exchange and injection of 25 mg of recombinant tPA over the area of the occluded vein. Intraoperative sectioning of the common arteriovenous sheath was achieved in all 40 patients. Thrombus release was observed in 11 cases (27.5%) and was correlated with early surgery (P < 0.001) and better final visual recovery (P < 0.06). Optical coherence tomography showed macular thickness that decreased by greater than 40% in 31 patients (77.5%) compared with preoperatively, and correlated to postoperative visual acuity (P < 0.001). The mean visual acuity increased from 20/100 to 20/40, with 70% of patients gaining three or more lines of visual acuity (Pearson 0.378, P = 0.016). Surgical venous decompression and injection of recombinant tPA may effectively manage macular edema secondary to BRVO, thus improving anatomic and visual outcome. Early surgical intervention may obtain maximum final visual recovery.

Extension of ischemic therapeutic time window by a free radical scavenger, Edaravone, reperfused with tPA in rat brain

3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) is a free radical scavenger. We tested the hypothesis that combination treatment of Edaravone and recombinant tissue plasminogen activator (tPA) extends the therapeutic time window. Male Wistar rats were subjected to 1.5-, 3.0- or 4.5-hour middle cerebral artery (MCA) occlusion (MCAO) by a nylon thread. Animals were randomly divided into four groups. The Sham group rats were operated without MCAO and drug injection. In the Vehicle-treated group the same volume of saline was given every 1.5 hours from just after MCAO to just before reperfusion. In the Vehicle + tPA-treated group saline injection was given as above and tPA (5 mg/kg, i.v.) was given once just after reperfusion. Edaravone+tPA-treated group: Edaravone (3 mg/kg, i.v.) was given every 1.5 hours instead of saline and tPA injection as above. Survival rate, infarct size and evidence of apoptosis and hemorrhage were examined in the animals. Combining administration of Edaravone+tPAsignificantly increased survival rate after 3 hours of transient MCAO, and reduced infarct volume after 1.5 hours of transient MCAO compared with the vehicle or vehicle+tPAgroups. In Edaravone+tPA-treated group, the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) and 4-hydroxynonenal (4-HNE) positive cells were reduced at 16 hours after 3 hours of transient MCAO, but not in advanced glycation end products (AGEs) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Hemorrhage rate and the area decreased in the Edaravone+tPA-treated group. The combination therapy of Edaravone+tPA increased survival rate, and reduced the infarct volume and hemorrhage with reduction of lipid peroxidation. Therefore, Edaravone combination is expected to extend the therapeutic time window of tPA in the clinical situation.

Prevention of Symptomatic Vasospasm After Aneurysmal Subarachnoid Hemorrhage by Intraoperative Cisternal Fibrinolysis Using Tissue-Type Plasminogen Activator Combined With Continuous Cisternal Drainage

The efficacy of intraoperative cisternal irrigation using tissue-type plasminogen activator (tPA) combined with continuous cisternal drainage was assessed for the prevention of symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). Seventy consecutive patients underwent direct surgery for aneurysm clipping within 48 hours of SAH and had computed tomography (CT) findings classified as Fisher group III or IV with densities of more than 65 Hounsfield units (HU). Fibrinolysis of the cisternal clots was performed during surgery using 1.6 mg tPA in 55 cases or 3.2 mg tPA in 15 cases. If postoperative CT within 24 hours of surgery showed areas with density more than 65 HU, additional tPA (0.8 mg/day) was administered into the cisternal catheter until the high density areas disappeared. The cisternal drainage catheters were left in place until day 14. Additional tPA injection was necessary in four of the 55 patients receiving 1.6 mg tPA. Symptomatic vasospasm occurred in three patients (4.3%) and two patients had low density areas on CT. Permanent deficit (hemiparesis) due to cerebral vasospasm remained in only one patient. Intraoperative cisternal irrigation with tPA combined with cisternal drainage is safe and effective for the prevention of symptomatic vasospasm following SAH.

Intravitreal tissue plasminogen activator in the management of central retinal vein occlusion.

To evaluate the role of intravitreal tissue plasminogen activator (tPA) in the management of central retinal vein occlusion (CRVO) in patients with symptoms for <3 days. We evaluated the visual outcome of a consecutive series of patients with CRVO following intravitreal tPA injection. All patients presented with visual acuity worse than 20/50 within 3 days from the onset of symptoms. Main outcome measures included percentage of patients whose final vision improved to 20/50 or better and change in percentage of patients with vision of 20/200 or worse before and after treatment. Twelve patients received intravitreal tPA for CRVO. Nine patients (75%) had best-corrected visual acuity of 20/200 or worse at presentation compared with 4 patients (33%) at the last follow-up after treatment. Five (55%) of these 9 patients had final visual acuity that improved to 20/50 or better. The remaining four patients did not have improvement or their vision continued to worsen. All 4 patients had fluorescein angiographic evidence of >10 disk areas of capillary nonperfusion at presentation. Overall, 8 (67%) of 12 patients had final visual acuity of 20/50 or better. No side effects related to tPA injection were observed. Our data suggest that intravitreal tPA injection may have a beneficial role in the management of CRVO when used within a few days of the onset of symptoms in patients with no angiographic evidence of severe capillary nonperfusion even if initial visual acuity is 20/200 or worse.

Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor–related protein

The regulation of cerebrovascular permeability is critical for normal brain homeostasis, and the “breakdown” of the blood-brain barrier (BBB) is associated with the development of vasogenic edema and intracranial hypertension in a number of neurological disorders. In this study we demonstrate that an increase in endogenous tissue-type plasminogen activator (tPA) activity in the perivascular tissue following cerebral ischemia induces opening of the BBB via a mechanism that is independent of both plasminogen (Plg) and MMP-9. We also show that injection of tPA into the cerebrospinal fluid in the absence of ischemia results in a rapid dose-dependent increase in vascular permeability. This activity is not seen with urokinase-type Plg activator (uPA) but is induced in Plg–/– mice, confirming that the effect is Plg-independent. However, the activity is blocked by antibodies to the LDL receptor–related protein (LRP) and by the LRP antagonist, receptor-associated protein (RAP), suggesting a receptor-mediated process. Together these studies demonstrate that tPA is both necessary and sufficient to directly increase vascular permeability in the early stages of BBB opening, and suggest that this occurs through a receptor-mediated cell signaling event and not through generalized degradation of the vascular basement membrane.

Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein.

The regulation of cerebrovascular permeability is critical for normal brain homeostasis, and the "breakdown" of the blood-brain barrier (BBB) is associated with the development of vasogenic edema and intracranial hypertension in a number of neurological disorders. In this study we demonstrate that an increase in endogenous tissue-type plasminogen activator (tPA) activity in the perivascular tissue following cerebral ischemia induces opening of the BBB via a mechanism that is independent of both plasminogen (Plg) and MMP-9. We also show that injection of tPA into the cerebrospinal fluid in the absence of ischemia results in a rapid dose-dependent increase in vascular permeability. This activity is not seen with urokinase-type Plg activator (uPA) but is induced in Plg-/- mice, confirming that the effect is Plg-independent. However, the activity is blocked by antibodies to the LDL receptor-related protein (LRP) and by the LRP antagonist, receptor-associated protein (RAP), suggesting a receptor-mediated process. Together these studies demonstrate that tPA is both necessary and sufficient to directly increase vascular permeability in the early stages of BBB opening, and suggest that this occurs through a receptor-mediated cell signaling event and not through generalized degradation of the vascular basement membrane.

Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes.

A fibrinolytic agent consisting of a tissue-type plasminogen activator (tPA) coupled to the surface of red blood cells (RBCs) can dissolve nascent clots from within the clot, in a Trojan horse-like strategy, while having minimal effects on preexisting hemostatic clots or extravascular tissue. After intravenous injection, the fibrinolytic activity of RBC-tPA persisted in the bloodstream at least tenfold longer than did that of free tPA. In a model of venous thrombosis induced by intravenously injected fibrin microemboli aggregating in pulmonary vasculature, soluble tPA lysed pulmonary clots lodged before but not after tPA injection, whereas the converse was true for RBC-tPA. Free tPA failed to lyse occlusive carotid thrombosis whether injected before or after vascular trauma, whereas RBC-tPA circulating before, but not injected after, thrombus formation restored blood flow. This RBC-based drug delivery strategy alters the fibrinolytic profile of tPA, permitting prophylactic fibrinolysis.

Treatment of Central Retinal Vein Occlusion by Vitrectomy with Lysis of Vitreopapillary and Epipapillary Adhesions, Subretinal Peripapillary Tissue Plasminogen Activator Injection, and Photocoagulation.

Abstract PURPOSE: To report a case of subretinal peripapillary tissue plasminogen activator (tPA) injection with vitreopapillary and epipapillary membrane dissection and peripheral photocoagulation in the treatment of central retinal vein occlusion. DESIGN: Interventional case report. METHODS: A 79-year-old woman with a history of branch vein occlusion in the left eye presented with visual loss in the right eye for 4 months secondary to unresolved central retinal vein occlusion. She underwent vitrectomy, right eye, with lysis of vitreopapillary and epipapillary adhesions and hyaloid separation, subretinal peripapillary tissue tPA injection, peripheral photocoagulation, and air-fluid exchange. RESULTS: Postoperatively, funduscopic and fluorescein angiographic features of venous obstruction improved rapidly, with prompt reduction in intraretinal hemorrhages and disk and macular edema. The patient reported subjective improvement of vision in her right eye, although measured improvement was modest, from finger counting to 20/400. CONCLUSION: Subretinal administration of tPA, lysis of adhesions, and endophotocoagulation may be of value in resolving the obstructive component of selected cases of chronic central retinal vein occlusion associated with vitreopapillary and epipapillary traction.

Retinal toxicity of intravitreal tissue plasminogen activator: Case report and literature review

Objective To present the clinical picture of retinal toxicity of commercial tissue plasminogen activator (tPA). Design Case report and literature review. Methods Two successive intravitreal injections of tPA (50 μg) 3 days apart with gas tamponade were given to treat a 49-year-old man with submacular hemorrhage. The adverse consequences of this treatment were monitored. A literature review of retinal toxicity of commercial tPA in animals was also done. Main outcome measures Retinal findings, electroretinograph (ERG) and visual acuity testing. Results Diffuse pigmentary alterations sparing the posterior pole, poor visual acuity after the absorption of submacular hemorrhage, reduced scotopic and photopic ERG A- and B-waves were noted. Conclusions This is the first reported case of retinal toxicity of commercial tPA in humans that resembles the descriptions of tPA-mediated retinal toxicity in animal models. The dosage of intravitreal tPA (between 50 and 100 μg) may be toxic to the human retina.

Intracameral tissue plasminogen activator use in a large series of eyes with valved glaucoma drainage implants.

To describe the efficacy and complications of intracameral tissue plasminogen activator (tPA) in a large series of glaucomatous eyes with valved glaucoma drainage implants (GDIs). A retrospective analysis of 620 Ahmed and Krupin aqueous shunts implanted between December 1992 and May 2001 identified 36 eyes treated with intracameral tPA for total or imminent tube obstruction by fibrin and/or blood. For a successful ocular outcome, tPA use must prevent the need for additional glaucoma surgery to replace or revise an occluded drainage implant. Intracameral tPA successfully cleared or prevented tube occlusion by fibrin/blood clots in 32 (88.9%) of 36 eyes. Multiple tPA injections were administered in 38.9% of eyes, and the mean number of injections required to achieve successful outcomes was 1.6. The mean +/- SD tPA dose per injection was 9.8 +/- 3.1 micro g, and the mean +/- SD total tPA dose required to achieve successful outcomes was 15.5 +/- 9.9 micro g. For injections to be successful in totally occluded tubes (n = 31), the mean +/- SD intraocular pressure change 24 hours after tPA administration was -21.2 +/- 15.6 mm Hg. Significant complications, including severe hyphema, profound hypotony, and anterior chamber flattening, occurred after 10.9% of tPA administrations. Intracameral tPA clears and prevents obstruction of valved GDIs by fibrin and/or blood clots.

Treatment of central retinal vein occlusion by vitrectomy with lysis of vitreopapillary and epipapillary adhesions, subretinal peripapillary tissue plasminogen activator injection, and photocoagulation

PURPOSE: To report a case of subretinal peripapillary tissue plasminogen activator (tPA) injection with vitreopapillary and epipapillary membrane dissection and peripheral photocoagulation in the treatment of central retinal vein occlusion. DESIGN: Interventional case report. METHODS: A 79-year-old woman with a history of branch vein occlusion in the left eye presented with visual loss in the right eye for 4 months secondary to unresolved central retinal vein occlusion. She underwent vitrectomy, right eye, with lysis of vitreopapillary and epipapillary adhesions and hyaloid separation, subretinal peripapillary tissue tPA injection, peripheral photocoagulation, and air-fluid exchange. RESULTS: Postoperatively, funduscopic and fluorescein angiographic features of venous obstruction improved rapidly, with prompt reduction in intraretinal hemorrhages and disk and macular edema. The patient reported subjective improvement of vision in her right eye, although measured improvement was modest, from finger counting to 20/400. CONCLUSION: Subretinal administration of tPA, lysis of adhesions, and endophotocoagulation may be of value in resolving the obstructive component of selected cases of chronic central retinal vein occlusion associated with vitreopapillary and epipapillary traction.

Intravitreous tissue plasminogen activator injection and pneumatic displacement in the management of submacular hemorrhage complicating scleral buckling procedures.

To evaluate the efficacy of recombinant tissue plasminogen activator (rTPA) and sulfur hexafluoride (SF6) in displacing submacular hemorrhage in patients who had scleral buckling procedures complicated by the development of submacular hemorrhage. Final visual acuity and complications of the procedures were evaluated. Sequential intravitreal injections of 50 microg rTPA in 0.1 mL and 0.4 cc SF6 were performed in eight patients who showed submacular hemorrhage 1 day after a scleral buckling procedure. The fundus was checked daily for 3 days after the injection of TPA and gas, and then was followed every week for 1 month and then every 2 months. Patients were observed for at least 6 months. Visual acuity and the status of complications were evaluated. Submacular hemorrhage was totally or partially displaced extramacularly in all patients on the day after rTPA and SF6 injection. Vitreous hemorrhage was present in all patients. The retina was attached in all patients and no recurrent retinal detachment was noted. Visual acuity was improved at 6 months after treatment in all seven of the patients with macula-off retinal detachments compared to the preoperative visual acuity. The last patient who had a macula-sparing retinal detachment had decreased vision (20/25) at 6 months compared to preoperatively. Recombinant tissue plasminogen activator and SF6 injection is an easy procedure that is less complicated than and as effective as internal drainage in patients with submacular hemorrhage developing as a complication of scleral buckling procedures.

Thrombolysis of Clotted Hemodialysis Grafts with Tissue-type Plasminogen Activator

To evaluate prospectively the efficacy of treating thrombosed hemodialysis arteriovenous polytetrafluoroethylene (PTFE) grafts using tissue-type plasminogen activator (tPA) and percutaneous transluminal angioplasty (PTA). Forty-two sequential thrombosed PTFE dialysis grafts in 33 patients presented for declotting. All 42 grafts were treated with a modified lysis and PTA technique with use of 2 mg tPA and 3,000-5,000 U heparin in a total volume of 5 mL, administered into the graft via an angiocatheter. The elapsed time from tPA injection until completion was recorded. Prospective data collection included demographic information, technical details of the procedure, immediate outcomes, complications, and patency rates. Technical success, defined as complete graft recanalization with a palpable thrill after treatment plus successful hemodialysis, was achieved in all cases, except five. These five cases were deliberate graft closures due to inadequacy of the outflow veins to support an arteriovenous graft after successful lysis. Mean lysis time was 40.8 minutes and mean room procedure time after the lysis period was 65.4 minutes. Eight procedure-related complications occurred (two major and six minor). The follow-up period was 4-241 days, with an estimated mean of 157 days. The 30-day and 90-day primary patency rates were 57% and 50%, respectively. Treatment of thrombosed PTFE dialysis grafts with use of 2 mg tPA and 3,000 U of heparin is safe and effective. Use of this modified lysis and PTA technique allows an expeditious procedure in the angiography suite. However, this technique precludes imaging of the outflow veins before treatment, so that grafts entering diffusely diseased veins may need to be closed after successful lysis.

The Effect of Tissue Plasminogen Activator on Premacular Hemorrhage

Early vitrectomy is recommended for eyes with premacular hemorrhage, which causes fibrovascular proliferation and macular traction. The purpose of this study was to investigate the therapeutic effects of tissue plasminogen activator (tPA) on premacular hemorrhage, and the clearing of hemorrhage from the macula. The authors injected tPA (25-37.5 microg) into the vitreous cavity of 13 eyes with premacular hemorrhage. The causes of premacular hemorrhage were diabetic retinopathy in 11 eyes and traumatic injuries in 2 eyes. Prior to tPA injection, 4 eyes had complete posterior vitreous detachment (PVD) and 9 eyes had no PVD. After tPA injection, the hemorrhages in 10 eyes were completely absorbed. They were absorbed partially in 2 eyes and were not absorbed at all in 1 eye. Absorption of hemorrhage in the 4 eyes with complete PVD took an average of 5.5 days, and in the 6 eyes with no PVD, it took an average of 12.7 days (P=0.002). After tPA injection, visual acuity improved in 9 eyes, remained stable in 3 eyes, and worsened in 1 eye. In 5 eyes, pars plana vitrectomy (PPV) was required after tPA injection because of recurrent vitreous hemorrhage, macular traction or nonabsorbed premacular hemorrhage. TPA seems to be a good alternative method of treatment for premacular hemorrhage, especially in eyes with complete PVD. It appears to improve vision and defer the need for PPV.

Treatment of recent onset central retinal vein occlusion with intravitreal tissue plasminogen activator: a pilot study

AIMSTo study the effects of intravitreal tissue plasminogen activator (tPA) in recent onset central retinal vein occlusion (CRVO).METHODS15 patients with recent onset CRVO (from 1–21 days' duration, mean 8 days)...

Retinal toxicity of commercial intravitreal tissue plasminogen activator solution in cat eyes.

We previously reported retinal toxic reactions in rabbit eyes receiving intravitreal injections of commercial tissue plasminogen activator (tPA) in concentrations greater than or equal to 50 microg/0.1 mL, and recent clinical experience suggests that intravitreal tPA solution may produce toxic effects in human eyes. We therefore investigated the dose-dependent retinal toxicity of intravitreal commercial recombinant tPA solution in cat eyes, which have a vascularized inner retina and vitreous volume similar to that of human eyes. Commercial tPA in L-arginine solution was injected into the mid vitreous cavity of normal cat eyes in doses of 25, 50, 75, and 100 microg/0.1 mL and 200 microg/0.2 mL. Control (fellow) eyes received an equal volume of sterile saline solution. After injection, eyes were evaluated by ophthalmoscopy and electroretinography for 14 days and then enucleated for histopathological evaluation. Fundus pigmentary alterations were observed in eyes receiving doses greater than or equal to 50 microg/0.1 mL. Changes were centered in the area around the injection site, and the area's size increased in proportion to the dosage. Mean electroretinography B-wave amplitude measured at 14 days was significantly reduced in eyes receiving greater than or equal to 50 microg of tPA in a dose-dependent fashion. Light microscopy of the involved areas showed loss of photoreceptor elements with necrosis and proliferation of the retinal pigment epithelium. Intravitreal injection of commercial tPA solution results in dose-dependent retinal toxicity in cat eyes. Because cat eyes are similar to human eyes regarding retinal vascularity and vitreous volume, intravitreal injections of commercial tPA (with L-arginine vehicle) in concentrations greater than 25 microg/0.1 mL are potentially unsafe in human eyes.