PMID- 29395119
OWN - NLM
STAT- MEDLINE
DCOM- 20190816
LR  - 20190816
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Linking)
VI  - 125
IP  - 5
DP  - 2018 May
TI  - Ranibizumab Plus Panretinal Photocoagulation versus Panretinal Photocoagulation 
      Alone for High-Risk Proliferative Diabetic Retinopathy (PROTEUS Study).
PG  - 691-700
LID - S0161-6420(17)32188-7 [pii]
LID - 10.1016/j.ophtha.2017.12.008 [doi]
AB  - PURPOSE: Comparison of the efficacy of ranibizumab (RBZ) 0.5 mg intravitreal 
      injections plus panretinal photocoagulation (PRP) versus PRP alone in the 
      regression of the neovascularization (NV) area in subjects with high-risk 
      proliferative diabetic retinopathy (HR-PDR) over a 12-month period. DESIGN: 
      Prospective, randomized, multicenter, open-label, phase II/III study. 
      PARTICIPANTS: Eighty-seven participants (aged >/=18 years) with type 1/2 diabetes 
      and HR-PDR (mean age, 55.2 years; 37% were female). METHODS: Participants were 
      randomized (1:1) to receive RBZ+PRP (n = 41) or PRP monotherapy (n = 46). The 
      RBZ+PRP group received 3 monthly RBZ injections along with standard PRP. The PRP 
      monotherapy group received standard PRP between day 1 and month 2; thereafter, 
      re-treatments in both groups were at the investigators' discretion. MAIN OUTCOME 
      MEASURES: The primary outcome was regression of NV total, on the disc (NVD) plus 
      elsewhere (NVE), defined as any decrease in the area of NV from the baseline to 
      month 12. Secondary outcomes included best-corrected visual acuity (BCVA) changes 
      from baseline to month 12, time to complete NV regression, recurrence of NV, 
      macular retinal thickness changes from baseline to month 12, need for treatment 
      for diabetic macular edema, need for vitrectomy because of occurrence of vitreous 
      hemorrhage, tractional retinal detachment or other complications of DR, and 
      adverse events (AEs) related to treatments. RESULTS: Seventy-seven participants 
      (88.5%) completed the study. Overall baseline demographics were similar for both 
      groups, except for age. At month 12, 92.7% of participants in the RBZ+PRP group 
      presented NV total reduction versus 70.5% of the PRP monotherapy participants 
      (P = 0.009). The number of participants with NVD and NVE reductions was higher 
      with RBZ+PRP (93.3% and 91.4%, respectively) versus PRP (68.8% and 73.7%, 
      respectively), significant only for NVE (P = 0.048). Complete NV total regression 
      was observed in 43.9% in the RBZ+PRP group versus 25.0% in the PRP monotherapy 
      group (P = 0.066). At month 12, the mean BCVA was 75.2 letters (20/32) in the 
      RBZ+PRP group versus 69.2 letters (20/40) in the PRP monotherapy group (P = 
      0.104). In the RBZ+PRP group, the mean number of PRP treatments over month 12 was 
      3.5+/-1.3, whereas in the PRP monotherapy group, it was 4.6+/-1.5 (P = 0.001). No 
      deaths or unexpected AEs were reported. CONCLUSIONS: Treatment with RBZ+PRP was 
      more effective than PRP monotherapy for NV regression in HR-PDR participants over 
      12 months.
CI  - Copyright (c) 2018 American Academy of Ophthalmology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Figueira, Joao
AU  - Figueira J
AD  - Association for Innovation and Biomedical Research on Light and Image (AIBILI), 
      Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 
      Department of Ophthalmology, Centro Hospitalar e Universitario de Coimbra (CHUC), 
      Coimbra, Portugal. Electronic address: joaofigueira@oftalmologia.co.pt.
FAU - Fletcher, Emily
AU  - Fletcher E
AD  - Department of Ophthalmology, Gloucestershire Hospitals, Gloucestershire, United 
      Kingdom.
FAU - Massin, Pascale
AU  - Massin P
AD  - Department of Ophthalmology, Lariboisiere Hospital, Paris, France.
FAU - Silva, Rufino
AU  - Silva R
AD  - Association for Innovation and Biomedical Research on Light and Image (AIBILI), 
      Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 
      Department of Ophthalmology, Centro Hospitalar e Universitario de Coimbra (CHUC), 
      Coimbra, Portugal; Coimbra Medical Space, Coimbra, Portugal.
FAU - Bandello, Francesco
AU  - Bandello F
AD  - Department of Ophthalmology University Vita-Salute, IRCCS San Raffaele Scientific 
      Institute, Milano, Italy.
FAU - Midena, Edoardo
AU  - Midena E
AD  - Centre for Clinical Trials, Department of Ophthalmology University of Padova, 
      Padova, Italy.
FAU - Varano, Monica
AU  - Varano M
AD  - G.B Bietti Eye Foundation, Rome-IRCCS, Italy.
FAU - Sivaprasad, Sobha
AU  - Sivaprasad S
AD  - Laser Retinal Research Unit, King's Health Partners, London, United Kingdom.
FAU - Eleftheriadis, Haralabos
AU  - Eleftheriadis H
AD  - Laser Retinal Research Unit, King's Health Partners, London, United Kingdom.
FAU - Menon, Geeta
AU  - Menon G
AD  - Ophthalmology Clinical Trials Unit Frimley, Frimley, United Kingdom.
FAU - Amaro, Miguel
AU  - Amaro M
AD  - Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal.
FAU - Ayello Scheer, Sarah
AU  - Ayello Scheer S
AD  - Centre d'Investigation Clinique, Centre National d'Ophthalmologie des 
      Quinze-Vingts, Paris, France.
FAU - Creuzot-Garcher, Catherine
AU  - Creuzot-Garcher C
AD  - Department of Ophthalmology University Hospital, CHU Dijon, France.
FAU - Nascimento, Joao
AU  - Nascimento J
AD  - Instituto de Retina e Diabetes Oculares de Lisboa, Lisbon, Portugal.
FAU - Alves, Dalila
AU  - Alves D
AD  - Association for Innovation and Biomedical Research on Light and Image (AIBILI), 
      Coimbra, Portugal.
FAU - Nunes, Sandrina
AU  - Nunes S
AD  - Association for Innovation and Biomedical Research on Light and Image (AIBILI), 
      Coimbra, Portugal.
FAU - Lobo, Conceicao
AU  - Lobo C
AD  - Association for Innovation and Biomedical Research on Light and Image (AIBILI), 
      Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 
      Department of Ophthalmology, Centro Hospitalar e Universitario de Coimbra (CHUC), 
      Coimbra, Portugal.
FAU - Cunha-Vaz, Jose
AU  - Cunha-Vaz J
AD  - Association for Innovation and Biomedical Research on Light and Image (AIBILI), 
      Coimbra, Portugal.
CN  - EVICR.net Study Group
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180201
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - ZL1R02VT79 (Ranibizumab)
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/*therapeutic use
MH  - Combined Modality Therapy
MH  - Diabetic Retinopathy/drug therapy/physiopathology/surgery/*therapy
MH  - Female
MH  - Fluorescein Angiography
MH  - Humans
MH  - Intravitreal Injections
MH  - Laser Coagulation/*methods
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Ranibizumab/*therapeutic use
MH  - Retinal Neovascularization/drug therapy/physiopathology/surgery/*therapy
MH  - Retreatment
MH  - Tomography, Optical Coherence
MH  - Vascular Endothelial Growth Factor A/antagonists & inhibitors
MH  - Visual Acuity/physiology
EDAT- 2018/02/06 06:00
MHDA- 2019/08/17 06:00
CRDT- 2018/02/04 06:00
PHST- 2017/07/13 00:00 [received]
PHST- 2017/11/10 00:00 [revised]
PHST- 2017/12/04 00:00 [accepted]
PHST- 2018/02/06 06:00 [pubmed]
PHST- 2019/08/17 06:00 [medline]
PHST- 2018/02/04 06:00 [entrez]
AID - S0161-6420(17)32188-7 [pii]
AID - 10.1016/j.ophtha.2017.12.008 [doi]
PST - ppublish
SO  - Ophthalmology. 2018 May;125(5):691-700. doi: 10.1016/j.ophtha.2017.12.008. Epub 
      2018 Feb 1.