Elsevier

Ophthalmology

Volume 122, Issue 2, February 2015, Pages 375-381
Ophthalmology

Original article
Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment: 5-Year Randomized Trial Results

https://doi.org/10.1016/j.ophtha.2014.08.047Get rights and content

Objective

To report 5-year results from a previously reported trial evaluating intravitreal 0.5 mg ranibizumab with prompt versus deferred (for ≥24 weeks) focal/grid laser treatment for diabetic macular edema (DME).

Design

Multicenter, randomized clinical trial.

Participants

Among participants from the trial with 3 years of follow-up who subsequently consented to a 2-year extension and survived through 5 years, 124 (97%) and 111 (92%) completed the 5-year visit in the prompt and deferred groups, respectively.

Methods

Random assignment to ranibizumab every 4 weeks until no longer improving (with resumption if worsening) and prompt or deferred (≥24 weeks) focal/grid laser treatment.

Main Outcome Measures

Best-corrected visual acuity at the 5-year visit.

Results

The mean change in visual acuity letter score from baseline to the 5-year visit was +7.2 letters in the prompt laser group compared with +9.8 letters in the deferred laser group (mean difference, −2.6 letters; 95% confidence interval, −5.5 to +0.4 letters; P = 0.09). At the 5-year visit in the prompt versus deferred laser groups, there was vision loss of ≥10 letters in 9% versus 8%, an improvement of ≥10 letters in 46% versus 58%, and an improvement of ≥15 letters in 27% versus 38% of participants, respectively. From baseline to 5 years, 56% of participants in the deferred group did not receive laser. The median number of injections was 13 versus 17 in the prompt and deferral groups, including 54% and 45% receiving no injections during year 4 and 62% and 52% receiving no injections during year 5, respectively.

Conclusions

Five-year results suggest focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better than deferring laser treatment for ≥24 weeks in eyes with DME involving the central macula with vision impairment. Although more than half of eyes in which laser treatment is deferred may avoid laser for at least 5 years, such eyes may require more injections to achieve these results when following this protocol. Most eyes treated with ranibizumab and either prompt or deferred laser maintain vision gains obtained by the first year through 5 years with little additional treatment after 3 years.

Section snippets

Methods

The study procedures have been reported1 and are summarized briefly. The study adhered to the tenets of the Declaration of Helsinki. The protocol and Health Insurance Portability and Accountability Act–compliant informed consent forms (the original study consent and extension study consent) were approved by institutional review boards. The protocol is available on the DRCR.net website (www.drcr.net; accessed June 13, 2014). In brief, participants had at least 1 eye with visual acuity

Results

After excluding deaths, the 5-year completion rate was 76% of the 163 original participants randomized to the ranibizumab + prompt laser group and 74% of the 150 original participants randomized to the ranibizumab + deferred laser group. Because the fourth and fifth years were extensions of the original study, some patients chose not to consent to the longer follow-up. Among those consenting and surviving through 5 years, the completion rate was ranibizumab plus prompt laser (97%) and

Discussion

When the DRCR.net reported the 1-year study results demonstrating an improvement in mean visual acuity in eyes with vision loss from DME involving the foveal center that had been treated with ranibizumab, the question of whether this improvement could be safely sustained over time and, if so, how many treatments were given within the DRCR.net protocol remained. Furthermore, the 1-year results did not suggest that prompt laser treatment added value when initiating ranibizumab compared with

References (6)

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Financial Disclosure(s): The author(s) have made the following disclosure(s): M.J.E.: grants − iCo Therapeutics, Jaeb Center; Consultant – Genentech; Payment for lecture including service on speaker's bureau – The Scienomics Group Bryn Mawr Communication.

N.M.B.: principal investigator − grants at The Johns Hopkins University sponsored by Bayer, Genentech, Inc., Novartis Pharma AG, Regeneron, and The Emmes Corporation through the Office of Research Administration of the Johns Hopkins University School of Medicine, and has a contract agreement from the American Medical Association to the Johns Hopkins University School of Medicine.

D.B.: royalties − Springer; grants − Aerpio, DRCR Network, Jaeb Center for Health Research, Inc., Novartis, and Regeneron; has provided expert testimony for Novartis; Consultant − Springer Inc., Alimera, and Novartis.

T.W.S.: grants − Eli Lilly, Emmes, Genentech, and Regeneron; Besse Medical.

Supported through cooperative agreements from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services (grant nos. EY14231, EY14229, EY18817, EY023207). The funding organization (National Institutes of Health) participated in oversight of the conduct of the study and review of the manuscript but not directly in the design or conduct of the study; in the collection, management, analysis, or interpretation of the data; or in the preparation of the manuscript. Genentech provided the ranibizumab for the study and funds to DRCR.net to defray the study's clinical site costs. As described in the DRCR.net Industry Collaboration Guidelines (available at www.drcr.net), the DRCR.net had complete control over the design of the protocol, ownership of the data, and all editorial content of presentations and publications related to the protocol. A complete list of all DRCR.net investigator financial disclosures can be found at www.drcr.net.

A published list of the Diabetic Retinopathy Clinical Research Network investigators and staff participating in this protocol can be found in Ophthalmology 2010;117:1064–77.e35 with a current list available at www.drcr.net.

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