title: The REVEAL Study: Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy in Asian Patients with Diabetic Macular Edema.
abstract: OBJECTIVE
  The primary study hypothesis was that ranibizumab 0.5 mg monotherapy or combined with laser is superior to laser monotherapy based on mean average change in best-corrected visual acuity (BCVA) over 12 months in Asian patients with visual impairment resulting from diabetic macular edema (DME).
  
  
  METHODS
  A 12-month, randomized, double-masked, multicenter, laser-controlled, phase III study.
  
  
  METHODS
  Three hundred ninety-six patients aged ≥18 years, with type 1 or 2 diabetes mellitus, BCVA of 78-39 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and visual impairment resulting from DME.
  
  
  METHODS
  Patients were randomized to ranibizumab + sham laser (n = 133), ranibizumab + active laser (n = 132), or sham injection + active laser (n = 131). Ranibizumab/sham injections were administered on day 1 and continued monthly. As of month 3, monthly injections were continued if stable vision was not reached. Treatment was reinitiated if BCVA decreased because of DME progression. Active/sham laser was administered on day 1 and thereafter according to ETDRS guidelines.
  
  
  METHODS
  Average change in BCVA from baseline to months 1 through 12, central retinal subfield thickness (CRST), and safety over 12 months.
  
  
  RESULTS
  Ranibizumab monotherapy or combined with laser was superior to laser in improving mean average change in BCVA from baseline to months 1 through 12 (+5.9 and +5.7 vs +1.4 letters). At month 12, greater proportion of patients gained ≥15 letters with ranibizumab and ranibizumab + laser compared with laser (18.8% and 17.8% vs 7.8%). Mean CRST reduced significantly from baseline to month 12 with ranibizumab (-134.6 μm) and ranibizumab + laser (-171.8 μm) versus laser (-57.2 μm). Patients received a mean of 7.8 and 7.0 ranibizumab injections in the ranibizumab and ranibizumab + laser arms, respectively, and 1.5-1.9 active laser across treatment arms over 12 months. Conjunctival hemorrhage was the most common ocular, whereas nasopharyngitis and hypertension were the most common nonocular adverse events. Ranibizumab was not associated with any cases of cerebrovascular hemorrhage and cerebrovascular ischemia. No death related to study treatment was reported.
  
  
  CONCLUSIONS
  Ranibizumab monotherapy or combined with laser showed superior BCVA improvements over laser treatment alone in Asian patients with visual impairment resulting from DME. No new ocular or nonocular safety findings were observed and treatment was well tolerated over 12 months.
authors.affiliation: Department of Ophthalmology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: Peking University People's Hospital, Beijing, China. Electronic address: dr_lixiaoxin@163.com.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Tan Tock Seng Hospital, Singapore, Republic of Singapore.
authors.forename: Adrian
authors.initials: A
authors.lastname: Koh
authors.affiliation: Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Timothy Y Y
authors.initials: TY
authors.lastname: Lai
authors.affiliation: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Fenq-Lih
authors.initials: FL
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Republic of Korea.
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Peking University Third Hospital, Beijing, China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Shiga University of Medical Science Hospital, Ohtsu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ohji
authors.affiliation: Department of Ophthalmology, Tan Tock Seng Hospital, Singapore, Republic of Singapore; National Healthcare Group Eye Institute, Singapore, Republic of Singapore.
authors.forename: Nikolle
authors.initials: N
authors.lastname: Tan
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Sung Bok
authors.initials: SB
authors.lastname: Cha
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Jila
authors.initials: J
authors.lastname: Shamsazar
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: C Lillian
authors.initials: CL
authors.lastname: Yau
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D044466:Asian People / Q000208:ethnology; D003131:Combined Modality Therapy; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000208:ethnology / Q000601:surgery / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008269:Macular Edema / Q000188:drug therapy / Q000208:ethnology / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000069579:Ranibizumab; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab