tPA: A (new) tool in the uveitis armamentarium for patient care

(Image Credit: AdobeStock/Marut)

Recombinant tissue plasminogen activator (tPA)—a molecule approved for the treatment of acute stroke by the FDA in 1996—remains ubiquitous in its primary use but has also found ancillary roles in treating pulmonary embolism and myocardial infarction and in clearing occluded intravenous lines.

Perhaps unknown to many, tPA also has a history of use in ophthalmology, as demonstrated by its appearance in ophthalmology order sets at academic centers or on the back shelves of eye clinics.

The intraocular use of tPA has been described for decades, possibly as early as 1989, according to the literature. Since then, it has been employed to treat intraocular fibrin of many etiologies, including post vitrectomy and for filtering blebs, submacular hemorrhage, and uveitis.^1-4 

This article showcases tPA’s potentially more widespread use in treating anterior chamber (AC) fibrin in cases of severe acute uveitis based on experience at the Shiley Eye Institute at the University of California, San Diego. Portions of this article are adapted from a presentation of the same title at the Sonoma Eye 2025 Meeting.⁵

Case highlight

Figure 1. A 27-year-old woman presenting with anterior chamber fibrin, pupillary membrane, and posterior synechiae due to a severe, first episode of acute unilateral anterior uveitis (ultimately determined to be due to HLA-B27).

A striking case is that of a 27-year-old woman presenting with a first episode of acute unilateral anterior uveitis (AU) (Figure 1). She was classically symptomatic with eye soreness, photophobia, and injection. Notably, she presented with counting fingers (CF) visual acuity due to a large fibrinous clot at the iris plane. She had been initially treated elsewhere for presumed conjunctivitis and then AU for a week total, presenting with worsening symptoms despite hourly prednisolone acetate 1% for 2 days.

Treatment

As is not uncommon at our practice, this patient was treated with an AC injection of tPA and given instructions to continue hourly prednisolone and start cycloplegics.

A standard AC tap set-up is utilized with a topical anesthetic, a topical betadine solution, an eyelid speculum, and a 30-gauge needle. A temporal limbal approach at the slit lamp is preferred if the patient can tolerate positioning. We typically inject 0.05 to 0.075 mL at a concentration of 25 to 50 µg/0.1 mL. An assistant, if available, may carefully depress the plunger as the needle is directed over the iris toward the primary accumulation of fibrin. The wound is burped on egress to equalize IOP.

Results

In all cases, we have observed complete dissolution of fibrin clots with this treatment, even within 1 hour of injection, with some patients reporting improved vision before leaving the office. In the past 3.5 years,
AC tPA has been administered more than
2 dozen times under departmental supervision, including by many residents. A handful of patients have presented with CF or worse vision (eg, hand motion), all improving to 20/50 or better Snellen visual acuity with resolution of posterior synechiae. This trend is echoed by several isolated reports and series that describe rapid response on the scale of hours to days and generally significantly improved visual acuity.

In the case above, the patient returned 4 days later with a clear pupillary axis and ultimately with 20/20 vision after tapering off topical steroids after 1 month (Figure 2).

Figure 2. After receiving an anterior chamber injection of tPA, the patient returned 4 days later with a clear pupillary axis and ultimately with 20/20 vision after tapering off topical steroids after 1 month.

(Images courtesy of Justin P. Ma, MD, and Doran B. Spencer, MD, PhD)

Clinical considerations

Apart from general precautions regarding behavioral and ocular structure considerations for the tap procedure, there is a theoretical relative contraindication in patients who may have acutely active intraocular bleeding. Nonetheless, in the case of a patient with a small nonexpansile hyphema and fibrin from severe anterior uveitis, AC tPA was well tolerated and effective without new bleeding. Although tPA is a molecule native to vascular endothelial cells, recombinant formulations for medical use pose similar risks for intolerance or sterile inflammation, as do other intraocular or intravitreal agents. However, we have not observed any secondary episodes of sterile intraocular inflammation in any of our patients treated with tPA. Large-scale investigation into the safety profile of this usage has not yet been made. Our isolated experience suggests good tolerance thus far.

Patient selection: Most patients who receive this treatment are ultimately found to have HLA-B27–associated noninfectious AU. Other etiologies include idiopathic AU and HSV-associated AU from severe exposure keratopathy and xerophthalmia due to vitamin A deficiency. In these conditions with significant fibrinous burden, tPA can have great benefit.

Implications: In cases of severe AU presenting with large fibrinous clots, topical steroids and cycloplegics alone often have limited success in completely reversing or preventing the structural complications from inflammation in the eye, including synechiae to the lens and in the angle, as well as pupillary membrane formation. Sparing patients from potentially severe vision loss due to these sequelae is an underappreciated benefit of using intracameral tPA broadly. In our experience, given the widespread use of tPA in inpatient settings for unclogging intravenous catheters, we typically receive a sufficient aliquot of tPA (0.1-0.3 mL) in a prefilled syringe from our inpatient pharmacy in 30 to 45 minutes at a cost of approximately $40.

Other uses: The literature^1-4 has described AC tPA in clearing fibrinous blockages in filtering glaucoma surgeries, uveitic cataracts, toxic anterior segment syndrome, and postvitrectomy anterior segment fibrin. In our department, AC tPA has been successfully utilized multiple times following YAG synechiolysis to prevent a pupillary membrane recurrence and clear the AC in the setting of acute endophthalmitis immediately before early vitrectomy.

Conclusion

Anterior chamber administration of tPA remains a treatment that is not commonly performed, even by many uveitis specialists. However, it has meaningful potential in improving vision and preventing complex surgical sequelae in some patients with severe acute AU. We hope this brief testimonial inspires our colleagues to consider adding this readily available and familiar tool to their armamentarium. A formal study of our patient cohort is forthcoming.

Justin P. Ma, MD

E: jpma@health.ucsd.edu

Ma is a resident physician at the
Shiley Eye Institute at the University of California, San Diego.

Doran B. Spencer, MD, PhD

E: dbspencer@ucsd.edu

Spencer is an assistant professor of ophthalmology and chief of the Uveitis Service with the Shiley Eye Institute at the University of California, San Diego, where he practices as a retina and uveitis specialist. Among his proudest professional accomplishments is inspiring (at least) 6 trainees to pursue uveitis training during his 6 years as a faculty member.

Neither author indicated any financial disclosures relevant to the subject matter.

References

1. Jaffe GJ, Lewis H, Han DP, Williams GA, Abrams GW. Treatment of postvitrectomy fibrin pupillary block with tissue plasminogen activator. Am J Ophthalmol. 1989;108(2):170-175. doi:10.1016/0002-9394(89)90013-5

2. Zalta AH, Sweeney CP, Zalta AK, Kaufman AH. Intracameral tissue plasminogen activator use in a large series of eyes with valved glaucoma drainage implants. Arch Ophthalmol. 2002;120(11):1487-1493. doi:10.1001/archopht.120.11.1487

3. Etheridge T, Hu WF, Larochelle M. Intracameral tissue plasminogen activator in uveitic cataract surgery. Invest Ophthal Vis Sci. 2022;63(7):3214–A0440. doi:10.1167/iovs0000000000003484

4. Osaadon P, Belfair N, Lavy I, et al. Intracameral r-tPA for the management of severe fibrinous reactions in TASS after cataract surgery. Eur J Ophthalmol. 2022;32(1):200-204. doi:10.1177/11206721211002064

5. Spencer D. TPA: a (new) tool in the uveitis armamentarium. Presented at: Sonoma Eye 2025 Meeting; March 20-23, 2025; San Diego, CA.