A factorial randomized controlled trial of tissue plasminogen activator and/or perfluoropropane for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration (TAPAS)

Title : A factorial randomized controlled trial of tissue plasminogen activator and/or perfluoropropane for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration (TAPAS)

Abstract:

Aim: To determine if intravitreal tissue plasminogen activator (TPA) or gas improves visual acuity and promotes resolution of submacular haemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD).
Methods: This randomised, multicentre, assessor-masked, sham-controlled, factorial, clinical trial and feasibility study recruited 56 participants with fovea-involving SMH of at least 1 disc area secondary to neovascular AMD, with onset within 14 days.  Study eyes received baseline ranibizumab and were then randomized 2:1:1:1 to one of four intravitreal treatments: sham injection, perfluoropropane (C₃F₈), TPA, or combined C₃F₈ and TPA (C₃F₈+TPA). All eyes received monthly pro re nata ranibizumab therapy over 12 months. The primary outcome measure was best-corrected visual acuity (BCVA) at month 3.
Results: On factorial analysis, the combined TPA groups had significantly better month 3 mean logMAR best-corrected visual acuity (BCVA) than those not receiving TPA: 0.66 vs 0.98 (μd = -0.32; 95% CI, -0.58 to -0.07; P = .02). There was no statistically significant difference comparing groups that did versus did not receive C₃F₈: 0.80 vs 0.90 (μd = -0.11; 95% CI, -0.37 to 0.16; P = .43). The combined TPA groups were less likely to have SMH present at month 1 (10 of 18 [55.6%] vs 21 of 24 [87.5%]; P = .03), a benefit not evident in the combined gas groups. The mean logMAR BCVA at 3 months was not significantly different between the individual groups: monotherapy control, 0.99; C₃F₈, 0.97 (vs control μd = -0.02; 95% CI, -0.48 to 0.44); TPA, 0.70 (vs control μd = -0.29; 95% CI, -0.79 to 0.21); combined C₃F₈ and TPA, 0.71 (vs control μd = -0.36; 95% CI, -0.82 to 0.11); P=0.11. No safety differences were identified across the treatment groups.
Conclusions:  Intravitreal TPA appears to drive more benefit that gas tamponade, when used alongside ranibizumab therapy. Further trials appear justified, and feasible.

Biography:

Professor Jackson is consultant ophthalmic surgeon at King’s College Hospital and professor of retinal research at King’s College London. He completed his medical degree in New Zealand, a retinal PhD at St Thomas’ Hospital, London, and his ophthalmology residency based in Moorfields Eye Hospital, where he completed his vitreoretinal fellowship. He has about 150 PubMed publications, is author of the Moorfields Manual of Ophthalmology, and has an approximately 6M Euros research portfolio.