Elsevier

Ophthalmology

Volume 124, Issue 1, January 2017, Pages 74-81
Ophthalmology

Original article
Randomized Trial of Treat and Extend Ranibizumab with and without Navigated Laser for Diabetic Macular Edema: TREX-DME 1 Year Outcomes

Presented in part at the Association for Research in Vision and Ophthalmology, May 2, 2016, Seattle, Washington, and the American Society of Retina Specialists, August 11, 2016, San Francisco, California. These data also will be presented as paper presentations at the annual meetings of The Retina Society and the American Academy of Ophthalmology.
https://doi.org/10.1016/j.ophtha.2016.09.021Get rights and content

Purpose

To compare monthly dosing with a treat and extend algorithm using ranibizumab 0.3 mg with and without angiography-guided macular laser photocoagulation for center-involving diabetic macular edema (DME).

Design

Multicenter, prospective, randomized clinical trial.

Participants

A total of 150 eyes from 116 subjects were randomized into 3 cohorts: Monthly (n = 30), TReat and EXtend without macular laser photocoagulation (TREX; n = 60), and treat and extend with angiography-GuIded macular LAser photocoagulation (GILA; n = 60).

Methods

Monthly cohort eyes received ranibizumab 0.3 mg every 4 weeks. Eyes in the TREX and GILA cohorts received 4 monthly injections of ranibizumab 0.3 mg followed by a treat and extend algorithm based on disease activity. Eyes in the GILA cohort also received angiography-guided macular laser photocoagulation at month 1 and again every 3 months for microaneurysm leakage.

Main Outcome Measures

Change in mean best-corrected visual acuity (BCVA), mean central retinal thickness (CRT), number of injections from baseline to 1 year, and percentage gaining/losing 2 and 3 lines of vision.

Results

Baseline demographics were well balanced among the cohorts. A total of 137 eyes (91%) completed the 1-year end point visit. At 1 year, the mean BCVA improved by 8.6, 9.6, and 9.5 letters in the Monthly, TREX, and GILA cohorts, respectively (P = 0.8). There was no significant difference between the cohorts in the percentage gaining/losing 2 and 3 lines of vision. The CRT improved by 123 μm, 146 μm, and 166 μm in the Monthly, TREX, and GILA cohorts, respectively (P = 0.47). The mean number of macular laser treatments in the GILA cohort at 1 year was 2.9 (range, 1–4). The number of injections was significantly reduced in both the TREX (10.7) and GILA (10.1) cohorts compared with the Monthly cohort (13.1, P < 0.001). There were no cases of endophthalmitis, and the total incidence of Anti-Platelet Trialists' Collaboration events was 4.7%.

Conclusions

This prospective, randomized trial found that treat and extend dosing of ranibizumab 0.3 mg with and without angiography-guided macular laser photocoagulation significantly decreased the number of injections given while providing similar visual and anatomic outcomes compared with monthly dosing at 1 year. Adding angiography-guided laser photocoagulation to this dosing algorithm did not significantly improve outcomes at 1 year.

Section snippets

Methods

The Treat and Extend Protocol in Patients with Diabetic Macular Edema (TREX-DME) is a phase I/II, multicenter, randomized, controlled clinical trial. The protocol was registered at www.clinicaltrials.gov (NCT01934556). The study protocol and procedures were approved by a centralized institutional review board and conducted at Palmetto Retina Center (West Columbia, SC), Retina Consultants of Houston (Houston, TX), and Retina-Vitreous Associates Medical Group (Los Angeles, CA). All study conduct

Results

A total of 150 eyes were enrolled between November 2013 and April 2015. Baseline demographics at screening were well balanced among the 3 cohorts (Table 1). At baseline, mean age was 59 years (range, 33–82 years), and 57% (68/119) were male. A total of 137 eyes (91%) completed the 1-year end point visit. At baseline, 14 (47%) Monthly eyes, 33 (55%) TREX eyes, and 32 (53%) GILA eyes had a BCVA worse than 20/40. In addition, 16 (53%) Monthly eyes, 40 (67%) TREX eyes, and 35 (58%) GILA eyes had a

Discussion

Although treat and extend dosing of anti-VEGF medications has been studied and is commonly used for neovascular age-related macular degeneration, this approach has not been rigorously investigated for DME.10 The current study, TREX-DME, is the first randomized, controlled trial assessing the efficacy of a treat and extend dosing strategy of ranibizumab 0.3 mg for DME. In TREX-DME, treat and extend dosing with and without navigated laser photocoagulation significantly decreased treatment burden

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Supplemental material is available at www.aaojournal.org.

Financial Disclosure(s): The author(s) have made the following disclosure(s): J.F.P.: Grants – Genentech, Regeneron, Alcon, Aerpio, EMMES.

C.C.W.: Grants – Alcon, Allergan, Bayer, Genentech, Regeneron, Roche, Allegro Ophthalmic, Apellis Pharmaceuticals, DRCR Network, Iconic Therapeutics; Personal fees – Alcon, Allergan, Alimera, Bayer, Genentech, Regeneron, Roche, Thrombogenics, Valeant.

W.L.C.: Grants – Regeneron, Genentech, Allergan; Personal fees – Bayer, Regeneron, Genentech, Santen, Ohr.

D.S.B.: Grants – Allergan, Aerpio, OHR, Regeneron, Genentech, River Vision, OD-OS, Kalvista; Personal fees – Allergan, Aerpio, Allegro, Bayer, OHR, Novartis, Regeneron, Genentech, Santen, River Vision, OD-OS.

D.M.B.: Grants – Alcon/Novartis, Allergan, Bayer, Genentech, Regeneron, Roche, Allegro Ophthalmic, Apelli Pharmaceuticals, DRCR Network, Iconic Therapeutics; Personal fees – Alcon/Novartis, Allergan, Alimera, Bayer, Genentech, Regeneron, Roche, Thrombogenics, Valeant.

Supported by a research grant from Genentech (grant no. ML28724). The funding organization had no role in the design or conduct of this research. Trial Registration: Registered at www.clinicaltrials.gov (NCT01934556).

Author Contributions:

Conception and design: Payne, Wykoff, Clark, Boyer, Brown

Data collection: Payne, Wykoff, Clark, Boyer, Brown

Analysis and interpretation: Payne, Wykoff, Clark, Bruce, Boyer, Brown

Obtained funding: Not applicable

Overall responsibility: Payne, Wykoff, Clark, Bruce, Boyer, Brown

Members of the TREX-DME Study Group available in the Appendix (www.aaojournal.org).

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