The RESTORE Study Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema

Centre for Vision Research (Westmead Millennium Institute), University of Sydney, Sydney, Australia.
Ophthalmology (Impact Factor: 6.17). 04/2011; 118(4):615-25. DOI: 10.1016/j.ophtha.2011.01.031
Source: PubMed

ABSTRACT To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME).
A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study.
We included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME.
Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits).
Mean average change in BCVA from baseline to month 1 through 12 and safety.
Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (-118.7 μm) and ranibizumab + laser (-128.3 μm) versus laser (-61.3 μm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study.
Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration.

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    ABSTRACT: Abstract: Diabetic macular oedema (DMO) is the most common cause of visual loss in the working age population. Intravitreal therapy has superseded macular laser as the firstline treatment for the management of centre-involving DMO in most patients. As well as the proven efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents, phase II and III clinical trials of Ozurdex intravitreal dexamethasone implants for DMO have also demonstrated a mean increase in visual acuity and corresponding mean reduction in central macular thickness, particularly in pseudophakic eyes. Because of the risk of visual loss from cataract, glaucoma and intraocular infection with the use of intravitreal steroids, Ozurdex tends to be reserved for use in patients unresponsive to anti-VEGF therapy for centre-involving DMO. Situations where Ozurdex may be considered a first-line treatment option for eyes with centre-involving DMO include pseudophakia, impending cataract surgery, or in the context of a recent arterial thromboembolic event. Because of their stable pharmacokinetics, Ozurdex slow-release implants may also be considered in vitrectomized eyes.
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    • "Ranibizumab (Lucentis ® ) is a recombinant humanized anti- VEGF mAb approved by EMA from 2007 for intravitreal treatment of neovascular age-related macular degeneration (http://www The effectiveness of ranibizumab in the treatment of age-related degeneration macular edema has been proven with large clinical trials [83] [84] "
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    • "Results of these studies were consistent across all subgroups of DME patients, including patients with focal or diffuse DME.13,14 However, patients with DME make up a heterogeneous group of patients with variable clinical manifestations. "
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    ABSTRACT: Background We evaluated the efficacy of intravitreal bevacizumab on diabetic macular edema with subfoveal and perifoveal hard exudates. Materials and methods Eleven eyes (11 patients) exhibiting diabetic macular edema with subfoveal and perifoveal hard exudates were included in this prospective, nonrandomized interventional pilot study. All patients were treated with monthly scheduled intravitreal bevacizumab injections for 6 months. Changes in the Early Treatment Diabetic Retinopathy Study best corrected visual acuity, amount of hard exudates on fundus photography, and macular edema detected by central subfield thickness on spectral domain optical coherence tomography after six serial injections, were assessed. The amount of hard exudates at each visit was evaluated as pixels in fundus photography, using an Adobe Photoshop program. Results Ten of 11 patients completed follow-up. The mean Early Treatment Diabetic Retinopathy Study best corrected visual acuity was 59.9±5.7 letters (Snellen equivalent, 20/63) at baseline evaluation. The best corrected visual acuity exhibited no significant difference at month 6 compared with at baseline (57.9±6.0 letters or 20/70 at month 6; P=0.085). At month 6, mean central subfield thickness decreased from 370.4±56.5 to 334.6±65.0 μm (P=0.009). The mean amount of hard exudates increased from 4467.1±2736.1 to 6592.4±2498.3 pixels at month 6 (P=0.022). No serious adverse events occurred. Conclusion Continuous intravitreal bevacizumab was found to have no benefit in visual acuity and amount of hard exudates, despite the improvement of macular edema at 6 months.
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