Literature Review of Recombinant Tissue Plasminogen Activator Used for Recent-Onset Submacular Hemorrhage Displacement in Age-Related Macular Degeneration

Abstract

Aims: To review and discuss the literature on recombinant tissue plasminogen activator (rtPA) for the treatment of a recent-onset submacular hemorrhage in patients with age-related macular degeneration. Methods: The administration technique of rtPA, the use of additional gas and vascular endothelial growth factor inhibitors (anti-VEGF), and the displacement rate of submacular hemorrhage and complications were noted from published reports, and a case series from the Rotterdam Eye Hospital (REH). Results: 38 studies with a total of 1,185 patients (1,176 eyes), and 28 patients from the REH were analyzed. Several methods for rtPA administration are available, which can be divided into two groups: submacular rtPA administration with vitrectomy; or intravitreal rtPA administration without vitrectomy. In both groups, the administration of gas and/or anti-VEGF agents could be additional. There appears to be no clear difference in complete displacement or complication rate between the more or the less invasive treatment groups. Conclusion: Although intravitreal injection of rtPA and gas only was reported to be as effective as subretinal rtPA with vitrectomy and gas, recent studies tend to use vitrectomy. These data underscore the need for a randomized controlled trial to choose the most effective and safe method of rtPA administration.

Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke

“…[365][366][367][368] Paradoxically, despite concerns over ocular hemorrhage after intravenous alteplase, intravitreal or subretinal alteplase injections, in conjunction with intravireal gas and vitrectomy, are reportedly used to improve visual acuity in instances of acute submacular hemorrhage. 369 A case report by Ahmad et al 370 describing a 70-year-old man presenting to hospital with an acute ischemic stroke for whom intravenous alteplase was withheld because of vitreous hemorrhage, citing the label that lists hemorrhagic ophthalmic conditions as a relative contraindication, drew considerable attention in the form of published correspondence, comments, and opinions. Sethi et al 371 posed the sensible question, "Would you save this patient's eye or his brain?"…”

Vitrectomy with subretinal tissue plasminogen activator and ranibizumab for submacular haemorrhages secondary to age-related macular degeneration: retrospective case series of 45 consecutive cases

“…12 Published case series of interventions to treat submacular haemorrhages often have fewer than 20 cases, and the end points are variable, including displacement of haemorrhage, change in visual acuity, or final vision. 13 In addition, it is not yet clear what risk factors at presentation may affect final outcome. It is likely that the size, and thickness, of the haemorrhage will affect the probability of visual recovery; 14 however, the thickness of the haemorrhage may be difficult to measure accurately with optical coherence tomography (OCT), as a dense haemorrhage may obscure the signal from the retinal pigment epithelium.…”

Prospective, Randomized Intervention Study Comparing Retinal Pigment Epithelium-Choroid Graft Surgery and Anti-VEGF Therapy in Patients with Exudative Age-Related Macular Degeneration

“…Nevertheless, it may be considered an alternative in the treatment of specific challenging cases in which no other treatment option is available, in patients with still relatively preserved retinal layers in the macular region. This might be the case in patients with a relatively fresh RPE-choroid tear, or a submacular hemorrhage which is too old to be treated with recombinant tissue plasminogen activator and/or too thick to be treated with anti-VEGF therapy [13]. In these patients, no therapy or removal of the hemorrhage alone has very poor results [5,6,7].…”

“…Inclusion criteria were: visual acuity (VA) loss of ≥15 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart after at least 3 anti-VEGF injections (referred to as ‘nonresponder'), subfoveal RPE tear, or a massive submacular hemorrhage (i.e., extending beyond the vascular arcades and/or a subfoveal thickness of at least 1.0 mm and no longer eligible for recombinant tissue plasminogen activator treatment) [13]. VA was between 20/63 and 20/800, and the patients were aged ≥50 years.…”