title: Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial.
abstract: OBJECTIVE
  To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy.
  
  
  METHODS
  A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 × 10(6) autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient.
  
  
  RESULTS
  No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 μV), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 μV) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms.
  
  
  CONCLUSIONS
  Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies.
authors.affiliation: Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirao Preto, Brazil.
authors.forename: Rubens C
authors.initials: RC
authors.lastname: Siqueira
authors.forename: André
authors.initials: A
authors.lastname: Messias
authors.forename: Julio C
authors.initials: JC
authors.lastname: Voltarelli
authors.forename: Ingrid U
authors.initials: IU
authors.lastname: Scott
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jorge
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D007208:Indocyanine Green; D058449:Intravitreal Injections; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D011446:Prospective Studies; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D041623:Tomography, Optical Coherence; D014182:Transplantation, Autologous; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields; D055815:Young Adult
chemical_list: D007208:Indocyanine Green