Article

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: 6.14). 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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Available from: Paul Mitchell, Nov 11, 2015
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    • "Focal/grid laser photocoagulation of leaking microaneurysms and areas of diffuse capillary bed leakage reduces the risk of moderate vision loss in DME [7], but it is often ineffective in restoring lost vision [8]. Anti-VEGF treatment with ranibizumab is more effective than laser in improving vision in patients with DME [9, 10], and anti-VEGF injections have become preferred first-line treatment for many patients [11] . The dosing frequency of anti-VEGF may be a treatment burden, however , as visual gains are most pronounced when monthly dosing is used (for example, in the phase 3 RISE/RIDE tri- als) [12]. "
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    ABSTRACT: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34–68 Early Treatment Diabetic Retinopathy Study letters (20/200–20/50 Snellen equivalent), and central retinal thickness (CRT) ≥300 μm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was ≥15-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n = 261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had ≥15-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was −126.1 μm with DEX 0.7 versus −39.0 μm with sham (P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population. Trial registration ClinicalTrials.gov NCT00168337 and NCT00168389, registered 12 September 2005
    Full-text · Article · Dec 2015 · BMC Ophthalmology
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    • "Anti-VEGF therapy A Cochrane review of anti-angiogenic therapy for DMO identified strong evidence of a clinical benefit in maintaining and improving vision using anti-VEGF drugs versus laser photocoagulation [Querques et al. 2009; Mitchell et al. 2011; Do et al. 2012; Rajendram et al. 2012; Virgili et al. 2014] "
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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.
    Full-text · Article · Aug 2015 · Therapeutic Advances in Cardiovascular Disease
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    • "In this study, we recruited patients from routine clinical care at two medium-sized county hospitals. Overall, the patient demographics, clinical characteristics, and visual functioning in the present clinical study were comparable with baseline characteristics in large pivotal clinical trials with ranibizumab for DME (Bressler et al., 2014; Mitchell et al., 2011). In the present study, we found a wide range in several baseline variables, such as age, glycosylated hemoglobin, weight, and blood pressure, which suggests heterogeneity among the included patients. "
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    ABSTRACT: To examine patient-reported outcome (PRO) in a selected group of Swedish patients about to receive anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). In this cross-sectional study, 59 patients with diabetes mellitus, who regularly visited the outpatient eye-clinics, were included. Sociodemographic and clinical data were collected and the patients completed PRO measures before starting anti-VEGF treatment. PRO measures assessed eye-specific outcomes (NEI-VFQ-25) and generic health-related quality of life (SF-36). The participants consisted of 30 men and 29 women (mean age, 68.5years); 54 (92%) patients had type 2 diabetes; 5 (9%) patients had moderate or severe visual impairment; 28 (47%) were classified as having mild visual impairment. Some of the patients reported overall problems in their daily lives, such as with social relationships, as well as problems with impaired sight as a result of reduced distance vision. Further studies are needed to investigate PRO factors related to low perceived general health in this patient population. It is important to increase our understanding of such underlying mechanisms to promote improvements in the quality of patient care. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Aug 2015 · Journal of diabetes and its complications
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