Intracameral recombinant tissue plasminogen activator (r-tPA) for refractory toxic anterior segment syndrome

Dotan, Assaf; Kaiserman, Igor; Kremer, I; Ehrlich, Rita; Bahar, Irit

doi:10.1136/bjophthalmol-2013-304294

Cited by 25 publications

(27 citation statements)

References 20 publications

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“…Por último, el uso de un activador de plasminógeno tisular recombinante (alteplase) intracameral, a la dosis de 25 ug/0,1 mL, usado en nuestra paciente en una sola aplicación, resulta eficaz en la membrana pupilar inflamatoria posquirúrgica, como demuestran los estudios al respecto (10,11) .…”

Section: Discussionunclassified

Adalimumab como alternativa terapéutica en el síndrome de Vogt Koyanagi Harada refractario al infliximab: reporte de caso

Ayre

Maldonado

2016

An Fac med

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ResumenEl síndrome de Vogt Koyanagi Harada (VKH) consiste en una panuveitis bilateral que forma parte de los síndromes uveomeníngeos. El tratamiento en estadio crónico es difícil por presentar pobre respuesta a la inmunomodulación, por lo que se recurre a opciones terapéuticas como agentes biológicos tipo anti-TNF alfa. Se describe el caso de una paciente con VKH severo y resistencia al infliximab, quien mostró respuesta al adalimumab. El adalimumab es un anticuerpo monoclonal humanizado efectivo en casos de resistencia al infliximab en pacientes con síndrome de VKH crónico persistente. El caso es de interés por ser infrecuente la resistencia a este medicamento en la práctica clínica, y el uso del activador de plasminógeno tisular contribuyó significativamente en la mejoría visual. Palabras clave. Síndrome Uveomeningoencefalítico, Vogt Koyanagi Harada; Adalimumab, Infliximab. Abstract Vogt Koyanagi Harada syndrome (VKH) is a bilateral panuveitis included in the uveomeningeal syndromes. Treatment of its chronic stage is difficult because of poor response to immunomodulation. Other therapeutic options include biological agents such as anti-TNF alpha. We present the case of a patient with severe VKH resistant to infliximab that responded to adalimumab. Adalimumab is a humanized monoclonal antibody effective when there is resistance to infliximab in patients with chronic persistent VKH syndrome. The case presented is interesting because of uncommon resistance to this drug in the clinical practice; the use of tissue plasminogen activator contributed significantly to visual improvement.

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Section: Discussionunclassified

Adalimumab como alternativa terapéutica en el síndrome de Vogt Koyanagi Harada refractario al infliximab: reporte de caso

Ayre

Maldonado

2016

An Fac med

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“…Recombinant biotechnology has produced several tPA variants, originally intended for intravenous use during acute treatment of myocardial infarction in people . Its applications have since expanded, and off‐label intraocular uses for tPA are numerous in both human and veterinary ophthalmology …”

Section: Introductionmentioning

confidence: 99%

“…In humans, most clinical reports of intracameral tPA administration evaluate its effect after fibrin has formed . A single report by Siatiri et al has examined the effect of prophylactic intracameral tPA, given at immediate conclusion of human pediatric cataract extraction and intraocular lens (IOL) implantation, since postoperative intraocular injections in children often require sedation.…”

Section: Introductionmentioning

confidence: 99%

Effect of immediate postoperative intracameral tissue plasminogen activator (tPA) on anterior chamber fibrin formation in dogs undergoing phacoemulsification

Mancuso

Nadelstein

Berdoulay

et al. 2019

Veterinary Ophthalmology

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Objective To evaluate the postoperative effect of intracameral tPA (alteplase; Activase®, Genentech, San Francisco, CA), administered at immediate conclusion of phacoemulsification, on anterior chamber fibrin formation in dogs. Procedures Forty‐one dogs (82 eyes) undergoing bilateral phacoemulsification received 25 μg/0.1 mL intracameral tPA in one eye and 0.1 mL unmedicated aqueous vehicle in the contralateral eye immediately after corneal incision closure. Intraocular pressure (IOP) was measured, and severity of anterior chamber fibrin formation, aqueous flare, pigment precipitates on the intraocular lens (IOL) implant, posterior capsular opacification (PCO), and corneal edema were graded at approximately 1 week, 2‐3 weeks, 4‐6 weeks, 8‐12 weeks, and greater than 3 months postoperatively. Results Anterior chamber fibrin developed postoperatively in 68.3% of dogs (28/41) and 50% of eyes (41/82). In tPA‐treated eyes, 53.7% (22/41) developed fibrin compared to 46.3% of control eyes (19/41). Some degree of postoperative ocular hypertension (POH) occurred in 53.7% of dogs (22/41) and 36.5% of eyes (30/82). In tPA‐treated eyes, 34.1% (14/41) experienced POH compared to 39% of control eyes (16/41). Additional intracameral tPA injection was later required in 29.3% of both tPA‐treated (12/41) and control eyes (12/41). Conclusions Administration of intracameral tPA at immediate conclusion of canine phacoemulsification had no clinically observable effect on anterior chamber fibrin incidence at any time point. tPA‐treated eyes showed no prophylaxis against POH or secondary glaucoma compared to control eyes and received late postoperative tPA injections at the same frequency as control eyes.

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“…Current clinical applications of tPA include cardiovascular emergencies [8] and various ocular disorders [9][10][11]. The rationale for its use in the eye is based on its thrombolytic activity as a serine protease, catalyzing the conversion of plasminogen to plasmin, an enzyme that degrades fibrin [12].…”

Section: Introductionmentioning

confidence: 99%

Retinal Penetration of Intravitreally Injected Tissue Plasminogen Activator: A Rat Model Study

Tal

Dotan²,

Nisgav³

et al. 2017

Ophthalmic Res

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Purpose: To determine whether intravitreal unconjugated tissue plasminogen activator (tPA) (alteplase) can penetrate the intact neural retina and reach the subretinal space in an experimental model. Methods: This study was performed in 24 Sprague-Dawley rats aged 12 weeks. Under general anesthesia, the right eye was injected with either 0.75 μg of 3 μL tPA (14 rats; study group) or saline (10 rats, control group) into the vitreous. Animals were euthanized at 3, 24, and 48 h. The eyes were enucleated, and cryosections were prepared for immunofluorescence staining. Goat anti-tPA antibody was used to detect tPA. Results: In the study group, staining for tPA was detected in the deep retinal layers in all eyes. The staining was deeper and more intense at 3 and 24 h than at 48 h. There was no tPA staining in the retina of eyes injected with saline. Conclusions: This experimental study shows that unconjugated tPA administered into the vitreous is capable of penetrating the deep retinal layers and the subretinal space. These findings suggest that further clinical research is warranted on the benefits of intravitreal tPA in the treatment of submacular hemorrhage.

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Intracameral recombinant tissue plasminogen activator (r-tPA) for refractory toxic anterior segment syndrome

Abstract: Intracameral injection of 25 µg r-tPA is safe and effective for the treatment of refractory fibrin reaction after cataract surgery.

Cited by 25 publications

References 20 publications

Adalimumab como alternativa terapéutica en el síndrome de Vogt Koyanagi Harada refractario al infliximab: reporte de caso

Adalimumab como alternativa terapéutica en el síndrome de Vogt Koyanagi Harada refractario al infliximab: reporte de caso

Effect of immediate postoperative intracameral tissue plasminogen activator (tPA) on anterior chamber fibrin formation in dogs undergoing phacoemulsification

Retinal Penetration of Intravitreally Injected Tissue Plasminogen Activator: A Rat Model Study

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