Intraocular tissue plasminogen activator concentrations after subconjunctival delivery

Area of Science:

• Ophthalmology
• Pharmacology
• Drug Delivery

Background:

• Topical administration of recombinant tissue plasminogen activator (tPA) yields detectable intraocular levels.
• The study investigated subconjunctival delivery as a method for enhanced intraocular drug penetration.

Purpose of the Study:

• To determine if subconjunctival administration of recombinant tPA enhances intraocular drug concentrations.
• To quantify tPA levels in the aqueous and vitreous humor following subconjunctival injection.

Main Methods:

• 16 rabbits underwent gas vitrectomy followed by subconjunctival injection of tPA (1 or 10 mg/ml) or sterile water in fellow eyes.
• Vitreous samples were collected for tPA concentration measurement.
• Anterior chamber paracentesis was performed at 15, 30, and 60 minutes post-injection; concentrations were measured using ELISA.

Main Results:

• Vitreous tPA levels were significantly higher than aqueous levels in treated eyes.
• Average vitreous tPA concentrations were 7 ± 7 ng/ml (1 mg/ml group) and 202 ± 230 ng/ml (10 mg/ml group).
• Detectable aqueous tPA levels were observed in 8 out of 16 samples.

Conclusions:

• Subconjunctival delivery of recombinant tPA leads to measurable concentrations in both the vitreous and aqueous humor.
• This route of administration shows potential for achieving intraocular therapeutic levels of tPA.