Publications
Primary End Point (Six Months) Results of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study
Quan Dong Nguyen, MD, MSc, Syed Mahmood Shah, MBBS, Jeffery S. Heier, MD, Diana V. Do, MD, Jennifer Lim, MD, David Boyer, MD, Prema Abraham, MD, Peter A. Campochiaro, MD, for the READ-2 Study Group
Objectives: To compare ranibizumab with focal/grid laser or a combination of both in diabetic macular edema (DME).
Design: Prospective, randomized, interventional, multicenter clinical trial.
Participants: A total of 126 patients with DME.
Methods: Subjects were randomized 1:1:1 to receive 0.5 mg of ranibizumab at baseline and months 1, 3, and 5 (group 1, 42 patients), focal/grid laser photocoagulation at baseline and month 3 if needed (group 2, 42 patients), or a combination of 0.5 mg of ranibizumab and focal/grid laser at baseline and month 3 (group 3, 42 patients).
Main Outcome Measures: The primary end point was the change from baseline in best-corrected visual acuity (BCVA) at month 6.
Results: At month 6, the mean gain in BCVA was significantly greater in group 1 ( 7.24 letters, P 0.01,analysis of variance) compared with group 2 ( 0.43 letters), and group 3 ( 3.80 etters) was not statistically different from groups 1 or 2. For patients with data available at 6 months, improvement of 3 lines or more occurred in 8 of 37 (22%) in group 1 compared with 0 of 38 (0%) in group 2 (P 0. 002, Fisher exact test) and 3 of 40 (8%) in group 3. Excess foveal thickness was reduced by 50%, 33%, and 45% in groups 1, 2, and 3, respectively.
Conclusions: During a span of 6 months, ranibizumab injections by the current protocol had a significantly better visual outcome than focal/grid laser treatment in patients with DME.
Vascular Endothelial Growth Factor Is a Critical Stimulus for Diabetic Macular Edema
Quan Dong
Nguyen, MD, MSC, Sinan Tatlipinar, MD, Syed Mahmood Shah,
MBBS, Julia A. Haller, MD,
Edward Quinlan, MD, Jennifer Sung, MD, Ingrid Zimmer-Galler, MD,
Diana V. Do, MD, and Peter A. Campochiaro, MD
Purpose: The role of vascular endothelial growth factor (VEGF) in diabetic macular edema (DME) was tested with ranibizumab, a specific antagonist of VEGF.
Design: A nonrandomized clinical trial.
Methods: Ten
patients with chronic DME received intraocular injections of 0.5 mg
of ranibizumab at baseline and at one, two, four, and six months.
The primary outcome was change in foveal thickness between baseline
and seven months, and the secondary outcome measures were changes
from baseline in visual acuity and macular
volume.
Results: Mean values at baseline were 503 m for foveal thickness, 9.22 mm3 for macular volume, and 28.1 letters (20/80) read on an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. At seven months (one month after the fifth injection), the mean foveal thickness was 257 m, which was a reduction of 246 m (85% of the excess foveal thickness present at baseline; P .005 by Wilcoxon signed-rank test for likelihood that this change is due to ranibizumab rather than chance). The macular volume was 7.47 mm3, which was a reduction of 1.75 mm3 (77% of the excess macular volume at baseline; P .009). Mean visual acuity was 40.4 letters (20/40), which was an improvement of 12.3 letters (P .005). The injections were well-tolerated with no ocular or systemic adverse events.
Conclusion: Intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in 10 patients with DME, which demonstrated that VEGF is an important therapeutic target for DME. A randomized, controlled, double masked trial is needed to test whether intraocular injections of ranibizumab provide long-term benefit to patients with DME.
A Pilot Study of Multiple Intravitreal Injections of Ranibizumab in Patients with Center-Involving Clinically Significant Diabetic Macular Edema
Dal W. Chun, MD, Jeffrey S. Heier, MD
Trexler M. Topping, MD,, Jay S. Duker, MD, Joy M. Bankert, RN, BSN
Objective: To evaluate the biologic activity of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic macular edema (DME) and to report any associated adverse events.
Design: Single-center, open-label, dose-escalating pilot study.
Participants: A total of 10 eyes of 10 patients (mean age, 69.3 years [range, 59–81]) with DME involving the center of the macula and best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400.
Intervention: Three intravitreal injections of ranibizumab (0.3 mg or 0.5 mg each injection) administered on day 0, month 1, and month 2, and observation until month 24.
Main Outcome Measures: Primary end points were the frequency and severity of ocular and systemic adverse events. Secondary end points were BCVA and measurement of retinal thickness by optical coherence tomography
Results: Of the 10 patients enrolled, 5 received 0.3-mg and 5 received 0.5-mg ranibizumab. Intravitreal injections of ranibizumab were well tolerated. No systemic adverse events were reported. Five occurrences of mild to moderate ocular inflammation were reported. At month 3, 4 of 10 patients gained 15 letters, 5 of 10 gained 10 letters, and 8 of 10 gained 1 letters. At month 3, the mean decrease in retinal thickness of the center point of the central subfield was 45.3 196.3 m for the low-dose group and 197.8 85.9 m for the high-dose group.
Conclusions: Ranibizumab appears to be a well-tolerated therapy for patients with DME. This pilot study demonstrates that ranibizumab therapy has the potential to maintain or improve BCVA and reduce retinal thickness in patients with center-involved clinically significant DME.
Two-Year Outcomes of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study
Quan Dong Nguyen, MD, MSc, Syed Mahmood Shah, MBBS, Afsheen A. Khwaja, MD,
Roomasa Channa, MD, Elham Hatef, MD, Diana V. Do, MD, David Boyer, MD, Jeffery S. Heier, MD,
Prema Abraham, MD, Allen B. Thach, MD, Eugene S. Lit, MD, Bradley S. Foster, MD,
Erik Kruger, MD, Pravin Dugel, MD, Thomas Chang, MD, Arup Das, MD, Thomas A. Ciulla, MD,
John S. Pollack, MD, Jennifer I. Lim, MD, Dean Eliot, MD, Peter A. Campochiaro, MD,
for the READ-2 Study Group
Objective: To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME).
Design: Prospective, randomized, interventional, multicenter clinical trial.
Participants: One hundred twenty-six patients with DME.
Methods: Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ.
Main Outcome Measures: The mean change from baseline in best-corrected visual acuity (BCVA) at month 24.
Results: After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 m, 286 m, and 258 m for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 m or less was 36%, 47%, and 68%, respectively.
Conclusions: Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema.