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

doi:10.1016/j.ophtha.2011.01.031

Ophthalmology

Volume 118, Issue 4, April 2011, Pages 615-625

Presented in part at: WOC 2010, EURETINA 2010, and AAO 2010.

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Objective

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).

Design

A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study.

Participants

We included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME.

Methods

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).

Main Outcome Measures

Mean average change in BCVA from baseline to month 1 through 12 and safety.

Results

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.

Conclusions

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.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

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: Appendix 4 contains a list of the primary investigators who participated in this study (available online at http://aaojournal.org).

: The authors thank Aditi Gandhe (Novartis Healthcare Private Ltd., India) for her medical writing and editorial assistance and Shivani Mittra (Novartis Healthcare Private Ltd., India) for her contribution toward various drafts of this manuscript.

: Manuscript no. 2010-1525.

: Financial Disclosure(s): The authors have made the following disclosures:

: P. Mitchell – Novartis – Consultant, Lecturer; Pfizer – Consultant, Lecturer; Allergan – Consultant; Solvay – Consultant; Bayer – Consultant.

: F. Bandello – Novartis – Consultant, Lecturer; Allergan – Consultant, Lecturer; Thea – Consultant, Lecturer.

: U. Schmidt-Erfurth – Alcon Laboratories, Inc. – Consultant, Lecturer; Bayer Healthcare – Consultant, Lecturer; Novartis – Consultant, Lecturer; Regeneron – Lecturer; Pfizer – Lecturer.

: P. Massin – Novartis – Consultant, Lecturer; Allergan – Consultant, Lecturer; Fovea Pharmaceutical – Consultant; Sanofi Aventis – Consultant; Takeda – Consultant, Lecturer.

: R.O. Schlingemann – Novartis – Consultant, Lecturer; Bayer Healthcare – Consultant.

: F. Sutter – Novartis – Consultant.

: G. Burian – Novartis Pharma – Employee.

: O. Gerstner – Novartis Pharma – Employee.

: A. Weichselberger – Novartis Pharma – Employee.

: Sponsored by Novartis Pharma AG, Switzerland. The study is registered with www.clinicaltrial.gov under number NCT00687804.

^⁎: Group members listed online in Appendix (available at http:///aaojournal.org)