The Role of Navigated Laser in TREX-DME

The 3-year results of the TREX-DME trial were recently published. This is a short summary on the role of laser in this multicenter study

 

The study compared a monthly treatment regimen with ranibizumab 0.3 mg to a Treat-and-Extend (TREX) regimen. Investigators added another arm to the protocol to study the effects of combining the treat and extend regimen with angiography-guided laser (GILA arm), using the Navilas® navigated laser.

The results demonstrate that treat and extend dosing, in this case with ranibizumab, provided similar visual and anatomic outcomes to monthly therapy and is a valuable approach to reduce injection burden for patients.

There was also a trend where there were benefits of combining the angiography-guided Navilas® laser with the TREX dosing regimen in terms of:

  1. Reduced treatment burden
  2. Better anatomic outcomes
  3. No compromise on visual acuity

However, in the TREX-DME protocol, these benefits were not statistically significant. This was potentially due to a strictly defined injection scheme with a high minimum number of mandatory injections, especially in the first year of the study.
 

Overview of results of GILA arm in the TREX-DME trial

(extracted from publications on 2-year and 3 year-data) 1)2)
 

Trend towards reduced treatment burden in the GILA arm

The average number of injections in year 3 for the GILA cohort was lower with an average of 2.4 injections
(compared to 3.1 and 3.0 for the TREX and monthly injection groups, respectively [p=0.56]). When looking at all three years, there was a reduction of 2.1 injections in the GILA cohort compared to the TREX cohort (19.9 injections versus 22 injections).

Additionally, 27% in the laser group did not require additional injections in year 3 compared to 11% in the TREX group. Likewise, the proportion of patients requiring “rescue” focal laser treatment in year 3 in the TREX arm was twice as high as in the GILA arm (36% vs. 18%).

 

Trend towards better anatomic outcomes in the GILA arm

The mean reduction in central retinal thickness (CRT) in the GILA cohorts was 165 µm, compared to 138 µm and 129 µm in the TREX and monthly cohorts (p=0.39).

This improved anatomic outcome may predict fewer future injections as the study found that eyes with thicker CRT at week 104 required more injections in the third year of the study (mean of 1.2 injections per 50 µm increase in CRT).
 

There was no compromise on visual acuity in GILA arm

Navigated laser did not compromise visual acuity (VA) at any time point. The mean change in best corrected visual acuity in the GILA cohort at the end of year 3 was + 9.5 letters and therefore better than the monthly ranibizumab cohort and very similar to the TREX cohort (+6.9 letters in the monthly cohort vs. + 9.7 letters in the TREX cohort).

 

  MonthlyTREXGILA
Cumulative Treatment BurdenCumulative injections per subject at end of Y327.72219.9
 Cumulative laser treatments per subject at end of Y30.10.65.2
 Total estimated treatment cost (U.S., $2150 per injection, $500 per laser)$59,600$46,600$45,400
Cumulative Clinical Benefit

Cumulative VA improvement at end of Y3 (letters)

6.99.79.5
 Cumulative CRT improvement at end of Y3 (microns)129138165
Treatment Burden in Y3% Eyes receiving no injection in Y3291127
 % Eyes receiving no laser in Y3926482

TREX-DME study protocol

The study followed a strict randomized protocol in 3 different sites over 3 years. In the first two years patients received mandatory injections according to the study protocol (Range: 8-13 injections in year 1 and 4-12 injections in year 2). All patients in all arms received the same baseline injection treatment with monthly injections for 4 doses. After the 4 loading doses of ranibizumab, eyes in the TREX and GILA cohorts were eligible to begin the treat & extend dosing regimen if their CRT was < 325 µm.  Additionally, all eyes in the GILA cohort received navigated focal laser treatment at week 4 and again every 3 months if there was leakage present on fluorescein angiography.

In the 3rd year, patients were treated as needed with ranibizumab if there was > 5 letters of vision loss or if the CRT was > 325 µm.  Also, all eyes were eligible to receive navigated focal laser treatment in the third year if they had required 2 intravitreal injections of ranibizumab over the preceeding 90-day period.

 

Discussion

The 3-year TREX-DME data demonstrated that the use of the Navilas® navigated laser resulted in an overall larger reduction in central retinal thickness, which in turn may lead to fewer future injections without compromising visual acuity.  The protocol had a pre-defined injection algorithm and at the end of year 3, this trend of reduced treatment burden was not statistically significant. Interestingly, 36% of the TREX eyes (which did not receive navigated laser treatment in the first two years) required rescue focal laser therapy in the third year compared to only 18% in the GILA cohort.  This suggests that the laser treatment had a protective effect on the retinal vasculature which led to decreased leakage and edema for some patients when the anti-VEGF effect had worn off. 

 

Navilas® as a research tool with the trial

The Navilas® technology allows pre-planning of laser directly on fluorescein angiogram and OCT macular maps. With Navilas® researchers can precisely track the laser plan and delivery of these targeted laser spots and patterns. All this with comprehensive digital documentation capabilities which provide the optimal foundation to analyze the results.

The Navilas laser also helped maintain consistency between the three study sites. 
 

 

Resources

1) Long-term outcomes of treat-and-extend ranibizumab with and without navigated laser for diabetic macular oedema: TREX-DME 3-year results. https://www.ncbi.nlm.nih.gov/pubmed/32303499

2) Randomized Trial of Treat and Extend Ranibizumab With and Without Navigated Laser Versus Monthly Dosing for Diabetic Macular Edema: TREX-DME 2-Year Outcomes.https://www.ncbi.nlm.nih.gov/pubmed/30771333

3) 3-year-data of combined navigated laser photocoagulation (Navilas) and intravitreal ranibizumab compared to ranibizumab monotherapy in DME patients. Herold, T. R., Langer, J., Vounotrypidis, E., Kernt, M., Liegl, R., & Priglinger, S. G. (2018). PloS one13(8), e0202483. PubMed PMID: 30138384

4) Blindbæk SL, Peto T, Grauslund J. Aflibercept and navigated versus conventional laser in diabetic macular oedema: a 12‐month randomized clinical trial. Acta Ophthalmol. October 2019:aos.14266. doi:10.1111/aos.14266

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