title: Intravitreal Tissue Plasminogen Activator, Ranibizumab, and Gas Injection for Submacular Hemorrhage in Polypoidal Choroidal Vasculopathy.
abstract: To investigate the efficacy of intravitreal injection of recombinant tissue plasminogen activator (rt-PA), ranibizumab, and gas without vitrectomy for submacular hemorrhage.
  
  
  
  Prospective, interventional, consecutive case series.
  
  
  
  Twenty consecutive patients (20 eyes) with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV).
  
  
  
  Ranibizumab, rt-PA (25 μg/0.05 ml), and 100% perfluoropropane (0.3 ml) were injected intravitreally, followed by 2-day prone positioning.
  
  
  
  The primary outcome measure was best-corrected visual acuity (BCVA) 6 months after treatment. Secondary outcome measures included central retinal thickness (CRT), central pigment epithelial detachment (PED) thickness, central ellipsoid zone, recurrence rate, and complications.
  
  
  
  Underlying disease was exudative AMD in 1 eye and PCV in 19 eyes. Submacular hemorrhage ranged in size from 2 to 31 disc diameters. Complete displacement of submacular hemorrhage was achieved in 17 eyes (85%), and partial displacement was achieved in 3 eyes (15%). Snellen BCVA improved from 20/139 before treatment to 20/65 at 6 months (P = 0.0061). Mean change in Early Treatment Diabetic Retinopathy Study score from baseline was +13 letters (P = 0.0040). Mean CRT decreased from 599 μm before treatment to 208 μm at 6 months (P < 0.0001), and central PED thickness decreased from 188 to 88 μm (P = 0.0140). Three eyes developed vitreous hemorrhage, and 1 eye developed retinal detachment; all were treated surgically, and Snellen BCVA improved at 6 months (P = 0.0012). Recurrence was observed in 10 eyes (50%) within 6 months, but visual acuity was preserved with intravitreal injection of anti-vascular endothelial growth factor (VEGF) pro re nata (PRN). The factors that affect BCVA at 6 months after treatment were pre- and posttreatment central ellipsoid zone (P = 0.0366 and P = 0.0424), pretreatment BCVA (P = 0.0015), and pre- and posttreatment central PED thickness (P = 0.0046, P = 0.0021).
  
  
  
  Subretinal hemorrhage treatment by intravitreal injection of rt-PA, ranibizumab, and gas is useful to achieve hemorrhage displacement and lesion improvement. To preserve visual acuity, early detection of posttreatment recurrence and intravitreal anti-VEGF injection PRN are necessary.
authors.affiliation: Department of Ophthalmology, School of Medicine, Nihon University, Kanda, Chiyodaku, Tokyo, Japan.
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Department of Ophthalmology, School of Medicine, Nihon University, Kanda, Chiyodaku, Tokyo, Japan. Electronic address: sshimada@olive.ocn.ne.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Ophthalmology, School of Medicine, Nihon University, Kanda, Chiyodaku, Tokyo, Japan.
authors.forename: Ryusaburo
authors.initials: R
authors.lastname: Mori
authors.affiliation: Department of Ophthalmology, School of Medicine, Nihon University, Kanda, Chiyodaku, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Ophthalmology, School of Medicine, Nihon University, Kanda, Chiyodaku, Tokyo, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Yuzawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D020256:Choroidal Neovascularization / Q000150:complications*; D003131:Combined Modality Therapy; D058450:Endotamponade; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005451:Fluorescein Angiography; D005466:Fluorocarbons / Q000008:administration & dosage*; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D011127:Polyps / Q000150:complications*; D016684:Prone Position; D011446:Prospective Studies; D000069579:Ranibizumab / Q000627:therapeutic use*; D012166:Retinal Hemorrhage / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000150:complications
chemical_list: D020533:Angiogenesis Inhibitors; D005343:Fibrinolytic Agents; D005466:Fluorocarbons; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C042852:perflutren; D010959:Tissue Plasminogen Activator; D000069579:Ranibizumab