The REVEAL Study

Ishibashi, Tatsuro; Li, Xiaoxin; Koh, Adrian; Lai, Timothy Y. Y.; Lee, Fenq-Lih; Lee, Won‐Ki; Ma, Zhizhong; Ohji, Masahito; Tan, Nicholas Y.Q.; Bok, Sung; Shamsazar, Jila; Yau, C. Lillian

doi:10.1016/j.ophtha.2015.02.006

Cited by 152 publications

(76 citation statements)

References 31 publications

(18 reference statements)

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“…There also was a significant correlation between the baseline BCVA and the BCVA at 1 month. As previously reported, the baseline BCVA might predict the functional outcome after IVR therapy [9, 11]. Taken together, we speculated that measuring the efficacy as early as 1 day after an IVR injection in patients with DME might be predictive of the structural and functional effects of the IVR injection in addition to the prediction from the baseline FT and BCVA.…”

Section: Discussionsupporting

confidence: 63%

“…The efficacy of intravitreal ranibizumab (IVR) (Lucentis, Novartis, Basel, Switzerland), a humanized affinity-matured vascular endothelial growth factor (VEGF) antibody fragment that specifically binds all isoforms of VEGF-A as a therapy for DME is now well established. Multiple randomized, controlled clinical trials, including the DRCR.net Protocol I [2, 3], RIDE and RISE [4, 5], READ 2 [6, 7], RESOLVE [8], RESTORE [9, 10], and REVEAL [11], have demonstrated visual improvement with IVR therapy. In these clinical trials, the first evaluations of the therapeutic effect on the foveal thickness (FT) and visual acuity (VA) were performed 1 week [8] or 1 month [2–7, 9–11] after injection of ranibizumab.…”

Section: Introductionmentioning

confidence: 99%

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Short-term effects of intravitreal ranibizumab therapy on diabetic macular edema

et al. 2017

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BackgroundThe short-term effects of intravitreal ranibizumab (IVR) on diabetic macular edema (DME) remains unclear. We assessed the short-term effects of IVR on DME.MethodsEighteen eyes of 14 patients with DME were enrolled in this prospective interventional case series. After intravitreal ranibizumab was injected into treatment-naïve eyes with DME, we measured the foveal thickness (FT) before and 2 h, 1 day, 1 week, and 1 month later and the best-corrected visual acuity (BCVA) at all times except 2 h and compared the changes to baseline (ΔFT and ΔVA).ResultsThe mean FT decreased significantly (p < 0.0001) from 452 ± 77 to 429 ± 65 microns after 2 h. The mean logarithm of the minimum angle of resolution BCVA improved significantly (p = 0.032) after 1 month from 0.41 ± 0.24 to 0.32 ± 0.21 (20/51 to 20/42, Snellen equivalent). The ΔFT after 2 h was significantly (r = 0.53, p = 0.025) correlated with the ΔFT after 1 month. The ΔVA after 1 day was significantly (r = 0.59, p = 0.01) correlated with the ΔVA after 1 month.ConclusionsThe structural effects of IVR for DME occurred within 2 h, whereas the functional effects occurred after 1 month. The short-term effects (within 1 day) of IVR may predict the therapeutic outcome 1 month after IVR in patients with DME.Trial registrationThe trial registration number: UMIN000026118 (Feb/13/2017). Retrospectively registered.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Short-term effects of intravitreal ranibizumab therapy on diabetic macular edema

et al. 2017

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“…In conclusion, a combination regimen of 1 + PRN-IVR and macular short-pulse focal/grid laser photocoagulation is likely to provide noninferior vision recovery as compared to previous reports of IVR monotherapy [16, 19]. The required number of IVR injections may be reduced in the combination treatment.…”

Section: Discussionmentioning

confidence: 73%

“…Several smaller clinical trials described an injection reduction in India [10], Japan [11, 12], Italy [13, 14], and Spain [15], but these were refuted by larger multicenter trials [1-5, 9, 16-18]. However, we have observed 3 possible conditions that may make focal/grid laser treatment effective: (1) prompt focal/grid laser after intravitreal injection of anti-VEGF agents [9, 18], (2) long follow-up [9, 18], and (3) focal but not diffuse DME [19]. …”

Section: Introductionmentioning

confidence: 99%

“…The REVEAL study showed that combination therapy of IVR and focal/grid laser photocoagulation provided better vision recovery (best-corrected visual acuity, BCVA, improvement: 7.8 letters) than did IVR alone (BCVA improvement: 5.9 letters) in a focal DME group. Moreover, the proportion of subjects with a treatment-free interval of 3 months or more was higher in the combination therapy arm (50.8%) than in the IVR monotherapy arm (38.3%) and significant only in eyes with focal DME [19]. …”

Section: Introductionmentioning

confidence: 99%

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Effect of Leaking Foveal Microaneurysms on the Treatment of Center-Involving Diabetic Macular Edema: A Pilot Study

et al. 2018

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Purpose: Evaluate the effect of foveal leaking microaneurysms (MAs) on the required number of intravitreal ranibizumab (IVR) injections in the treatment of center-involving diabetic macular edema (DME) when treated with focal/grid laser. Design: A pilot study of prospective, nonrandomized, multicenter clinical trial. Methods: This study enrolled 21 eyes with DME for which pro re nata IVR injections were combined with short-pulse focal/grid laser. At 12 months, best-corrected visual acuity (BCVA), central subfield macular thickness (CMT), and the required number of IVRs to maintain CMT < 300 µm were compared between eyes with or without foveal leaking MAs, termed the MA(+) and MA(–) groups, respectively. Results: Significant CMT improvements (p < 0.0001) and increased BCVA of 4.0 ± 8.5 letters were observed at 12 months. The MA(–) group required significantly fewer IVRs than did the MA(+) group (mean: 4.9 ± 3.0 vs. 8.6 ± 3.0; p = 0.0306). In the latter 6 months of the 1-year follow-up, 50% (4/8) of MA(–) eyes did not require any IVR administration to sustain CMT < 300 µm. Conclusions: A combination therapy of short-pulse focal/grid laser and reduced IVR injections appeared noninferior to previous reports of IVR monotherapy. Further large-scale investigations are warranted.

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Vascular Safety of Ranibizumab in Patients With Diabetic Macular Edema

Zarbin

Dunger-Baldauf

Hašková³

et al. 2017

JAMA Ophthalmol

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IMPORTANCE Patients with diabetic macular edema (DME) are at high risk of vascular complications, including stroke and myocardial infarction (MI). Concerns have been raised that intravitreal dosing of vascular endothelial growth factor inhibitors in DME could be associated with an increase in cardiovascular and cerebrovascular adverse events. OBJECTIVE To evaluate the cardiovascular and cerebrovascular safety of ranibizumab, 0.5 mg and 0.3 mg, compared with sham with and without laser in DME. DATA SOURCES Patient-level data from 6 randomized, double-masked, sham-and laser-controlled clinical trials. STUDY SELECTION Company-sponsored (Genentech or Novartis) studies in DME completed as of December 31, 2013. DATA EXTRACTION AND SYNTHESIS Pairwise comparisons (ranibizumab, 0.5 mg, vs sham and laser; ranibizumab, 0.3 mg, vs sham) were performed using Cox proportional hazard regression (hazard ratios, 95% CIs) and rates per 100 person-years. Data analysis was conducted from June 1 to July 15, 2015. MAIN OUTCOMES AND MEASURES Standardized Medical Dictionary for Regulatory Activities queries and extended searches were prospectively defined to identify relevant safety end points, including arterial thromboembolic events, MI, stroke or transient ischemic attack, vascular deaths, and major vascular events as defined by the Antiplatelet Trialists' Collaboration (APTC). RESULTS Overall, 936 patients were treated with ranibizumab, 0.5 mg; 250 patients with ranibizumab, 0.3 mg; and 581 patients with sham/laser. The hazard ratios associated with all pairwise comparisons included 1 for all key cardiovascular and cerebrovascular safety end points. For ranibizumab, 0.5 mg, vs sham/laser and ranibizumab, 0.3 mg, vs sham, the hazard ratios were, respectively, arterial thromboembolic events, 1.05 (95% CI, 0.66-1.68) and 0.78 (95% CI, 0.43-1.40); MI, 0.84 (95% CI, 0.41-1.72) and 0.94 (95% CI, 0.43-2.06); stroke or transient ischemic attack, 0.94 (95% CI, 0.44-1.99) and 0.53 (95% CI, 0.19-1.42); stroke (excluding transient ischemic attack), 1.63 (95% CI, 0.65-4.07) and 0.59 (95% CI, 0.14-2.46); vascular death, 2.17 (95% CI, 0.57-8.29) and 2.51 (95% CI, 0.49-12.94); and APTC-defined events, 1.09 (95% CI, 0.63-1.88) and 1.00 (95% CI, 0.51-1.96). CONCLUSIONS AND RELEVANCE This pooled analysis includes 1 of the largest patient-level data sets on treatment of DME with ranibizumab. Although still underpowered to detect small differences for infrequent events, such as stroke, the findings suggest that intravitreous ranibizumab does not increase the risk of systemic vascular events. However, uncertainty remains for patients with DME who are at high risk for vascular disease and were not included in these trials.

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The REVEAL Study

Cited by 152 publications

References 31 publications

Short-term effects of intravitreal ranibizumab therapy on diabetic macular edema

Short-term effects of intravitreal ranibizumab therapy on diabetic macular edema

Effect of Leaking Foveal Microaneurysms on the Treatment of Center-Involving Diabetic Macular Edema: A Pilot Study

Vascular Safety of Ranibizumab in Patients With Diabetic Macular Edema

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