title: Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME).
  
  
  OBJECTIVE
  To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy.
  
  
  METHODS
  Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015.
  
  
  METHODS
  Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME.
  
  
  METHODS
  The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization.
  
  
  RESULTS
  Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified.
  
  
  CONCLUSIONS
  Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01489189.
authors.affiliation: Carolina Retina Center PA, Columbia, South Carolina.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Gross
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Glassman
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Jampol
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Seidu
authors.initials: S
authors.lastname: Inusah
authors.affiliation: Joslin Diabetes Center, Beetham Eye Institute, Department of Ophthalmology, Harvard University, Boston, Massachusetts.
authors.forename: Lloyd Paul
authors.initials: LP
authors.lastname: Aiello
authors.affiliation: Charlotte Eye, Ear, Nose, and Throat Associates PA, Charlotte, North Carolina.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Antoszyk
authors.affiliation: Paducah Retinal Center, Paducah, Kentucky.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Baker
authors.affiliation: Retina Research Center, Austin, Texas.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Berger
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Bressler
authors.affiliation: Charlotte Eye, Ear, Nose, and Throat Associates PA, Charlotte, North Carolina.
authors.forename: David
authors.initials: D
authors.lastname: Browning
authors.affiliation: Elman Retina Group PA, Baltimore, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Elman
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.affiliation: Florida Retina Consultants, Lakeland.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Friedman
authors.affiliation: Southeast Retina Center PC, Augusta, Georgia.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Marcus
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Michele
authors.initials: M
authors.lastname: Melia
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Stockdale
authors.affiliation: Joslin Diabetes Center, Beetham Eye Institute, Department of Ophthalmology, Harvard University, Boston, Massachusetts.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Sun
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Roy W
authors.initials: RW
authors.lastname: Beck
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D019540:Area Under Curve; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D058449:Intravitreal Injections / Q000009:adverse effects; D008028:Light Coagulation / Q000009:adverse effects / Q000379:methods*; D008269:Macular Edema / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014792:Visual Acuity; D014821:Vitrectomy / Q000706:statistics & numerical data
chemical_list: D020533:Angiogenesis Inhibitors; D000069579:Ranibizumab