Randomized clinical trial evaluating intravitreal ranibizumab or saline for vitreous hemorrhage from proliferative diabetic retinopathy.
OBJECTIVE
Vascular endothelial growth factor plays a role in proliferative diabetic retinopathy (PDR). Intravitreal injection of saline has been shown potentially to lead to improved visual acuity compared with observation alone in eyes with vitreous hemorrhage. Therefore, it is important to determine if intravitreal anti-vascular endothelial growth factor can reduce vitrectomy rates (and risks associated with vitrectomy) compared with saline for vitreous hemorrhage from PDR that precludes placement or confirmation of complete panretinal photocoagulation.


OBJECTIVE
To evaluate intravitreal ranibizumab compared with intravitreal saline injections on vitrectomy rates for vitreous hemorrhage from PDR.


METHODS
Phase 3, double-masked, randomized, multicenter clinical trial. Data reported were collected from June 2010 to March 2012 and include 16 weeks of follow-up.


METHODS
Community-based and academic-based ophthalmology practices specializing in retinal diseases.


METHODS
Two hundred sixty-one eyes of 261 study participants, who were at least 18 years of age with type 1 or type 2 diabetes mellitus. Study eyes had vitreous hemorrhage from PDR precluding panretinal photocoagulation completion.


METHODS
Eyes were randomly assigned to 0.5-mg intravitreal ranibizumab (n = 125) or intravitreal saline (n = 136) at baseline and 4 and 8 weeks.


METHODS
Cumulative probability of vitrectomy within 16 weeks.


RESULTS
Cumulative probability of vitrectomy by 16 weeks was 12% with ranibizumab vs 17% with saline (difference, 4%; 95% CI, -4% to 13%) and of complete panretinal photocoagulation without vitrectomy by 16 weeks was 44% and 31%, respectively (P = .05). The mean (SD) visual acuity improvement from baseline to 12 weeks was 22 (23) letters and 16 (31) letters, respectively (P = .04). Recurrent vitreous hemorrhage occurred within 16 weeks in 6% and 17%, respectively (P = .01). One eye developed endophthalmitis after saline injection.


CONCLUSIONS
Overall, the 16-week vitrectomy rates were lower than expected in both groups. This study suggests little likelihood of a clinically important difference between ranibizumab and saline on the rate of vitrectomy by 16 weeks in eyes with vitreous hemorrhage from PDR. Short-term secondary outcomes including visual acuity improvement, increased panretinal photocoagulation completion rates, and reduced recurrent vitreous hemorrhage rates suggest biologic activity of ranibizumab. Long-term benefits remain unknown. Whether vitrectomy rates after saline or ranibizumab injection are different than observation alone cannot be determined from this study.


BACKGROUND
The study is listed on www.clinicaltrials.gov, under identifier NCT00996437 (website registration date October 14, 2009).
Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647, USA.
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab; D012008:Recurrence; D015861:Retinal Neovascularization / Q000150:complications*; D012965:Sodium Chloride / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014786:Vision Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology; D014821:Vitrectomy / Q000706:statistics & numerical data; D014823:Vitreous Hemorrhage / Q000188:drug therapy* / Q000209:etiology
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D012965:Sodium Chloride; D000069579:Ranibizumab