Elsevier

Ophthalmology

Volume 121, Issue 5, May 2014, Pages 1045-1053
Ophthalmology

Original article
Three-Year Outcomes of Individualized Ranibizumab Treatment in Patients with Diabetic Macular Edema: The RESTORE Extension Study

Data from this study were presented at: The Association for Research in Vision and Ophthalmology, May 6–10, 2012, Ft. Lauderdale, Florida; EASDec, May 25–27, 2012, Dublin, Ireland; Club Jules Gonin, June 20-23, 2012, Reykjavik, Iceland; EURETINA, September 6–9, 2012, Milan, Italy; European Association for the Study of Diabetes, October 1–5, 2012, Berlin, Germany; American Academy of Ophthalmology, November 10–13, 2012, Chicago, Illinois; and Asia Pacific Academy of Ophthalmology, January 17–20, 2013, Hyderabad, India.
https://doi.org/10.1016/j.ophtha.2013.11.041Get rights and content
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Objective

To evaluate long-term efficacy and safety profiles during 3 years of individualized ranibizumab treatment in patients with visual impairment due to diabetic macular edema (DME).

Design

Phase IIIb, multicenter, 12-month, randomized core study and 24-month open-label extension study.

Participants

Of the 303 patients who completed the randomized RESTORE 12-month core study, 240 entered the extension study.

Methods

In the extension study, patients were eligible to receive individualized ranibizumab treatment as of month 12 guided by best-corrected visual acuity (BCVA) and disease progression criteria at the investigators' discretion. Concomitant laser treatment was allowed according to the Early Treatment Diabetic Retinopathy Study guidelines. Based on the treatments received in the core study, the extension study groups were referred to as prior ranibizumab, prior ranibizumab + laser, and laser.

Main Outcome Measures

Change in BCVA and incidence of ocular and nonocular adverse events (AEs) over 3 years.

Results

Overall, 208 patients (86.7%) completed the extension study. In patients treated with ranibizumab during the core study, consecutive individualized ranibizumab treatment during the extension study led to an overall maintenance of BCVA and central retinal subfield thickness (CRST) observed at month 12 over the 2-year extension study (+8.0 letters, −142.1 μm [prior ranibizumab] and +6.7 letters, −145.9 μm [prior ranibizumab + laser] from baseline at month 36) with a median of 6.0 injections (mean, 6.8 injections; prior ranibizumab) and 4.0 (mean, 6.0 injections; prior ranibizumab + laser). In the prior laser group, a progressive BCVA improvement (+6.0 letters) and CRST reduction (−142.7 μm) at month 36 were observed after allowing ranibizumab during the extension study, with a median of 4.0 injections (mean, 6.5 injections) from months 12 to 35. Patients in all 3 treatment groups received a mean of <3 injections in the final year. No cases of endophthalmitis, retinal tear, or retinal detachment were reported. The most frequently reported ocular and nonocular adverse effects over 3 years were cataract (16.3%) and nasopharyngitis (23.3%). Eight deaths were reported during the extension study, but none were suspected to be related to the study drug/procedure.

Conclusions

Ranibizumab was effective in improving and maintaining BCVA and CRST outcomes with a progressively declining number of injections over 3 years of individualized dosing. Ranibizumab was generally well tolerated with no new safety concerns over 3 years.

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Financial Disclosure(s): The author(s) have made the following disclosure(s):

U.S.-E.: Bayer Health Care, Alcon, Novartis, Allergan, Boehringer (consultant fee).

G.E.L.: University Eye Hospital, Ulm (grant, consulting fee); Novartis (research grant, consultant, fees for lecture, clinical studies); Alcon (consultant); Allergan (clinical studies).

F.G.H.: Novartis (grant, support for travel to meetings for the study or other purposes, consulting fee); Heidelberg Engineering, Novartis, Pfizer, Acucela, Genentech, Alcon, Allergan (consultant); Novartis, GlaxoSmithKline, Alcon, Optos, Heidelberg Engineering, Carl Zeiss Meditec, Allergan (Grants); Alcon, Pfizer, Novartis, Heidelberg Engineering, Bayer Healthcare (lecture fees).

R.O.S.: Novartis, Boehringer Ingelheim (board membership); Novartis (grants, lecture fees, consulting fees).

P.L.: Alimera, Allergan, Alcon, Bayer, Novartis, Roche (personnel fees); Novartis (grants).

P.M.: Novartis, Allergan (board membership); Novartis, Allergan, Sanofi, Bayer (consultant).

O.G.: full-time employee of Novartis Pharma AG.

A.S.B.: full-time employee of Novartis Pharma AG. H.S.: full-time employee of Beijing Novartis Pharmaceuticals Co.

A.O.: full-time employee of Novartis Pharma AG. P.M.: Novartis, Bayer, Abbott (consultant, lecture fee).

Sponsored by Novartis Pharma AG, Switzerland, and the study is registered with http://clinicaltrials.gov/; accessed June 25, 2013 (NCT00906464).

Supplemental material is available at www.aaojournal.org.