The LUCIDATE study: a randomized clinical trial to evaluate the long-term functional and anatomical effects of repeated ranibizumab therapy compared with laser in diabetic macular edema

Abstract

 

Purpose

 

To determine the effect of repeated ranibizumab treatment on retinal function and morphology associated with diabetic macular edema (DME) and to identify factors that may be associated with a favourable treatment response.

 

Methods

 

Randomized controlled trial. 36 subjects with center-involving DME, BCVA 55-79 ETDRS letters, OCT central retinal thickness >300 µm and moderate macular ischemia only were randomized 2:1 to receive ranibizumab 0.5 mg (3 initial 4-weekly injections then prn retreatment) or modified ETDRS laser (at baseline and every 12 weeks if CSME present). Criteria included a foveal avascular zone (FAZ) <1000 µm and perifoveal capillary loss less than severe. Subjects underwent best-corrected ETDRS visual acuity, fluorescein angiography; Spectralis OCT; Nidek MP1 microperimetry; ChromaTest color contrast sensitivity; and pattern, full-field and multifocal electroretinography at baseline, 12, 24 and 48 weeks (primary endpoint for exploratory outcomes). Masked graders evaluated angiographic images for FAZ characteristics and OCT scans for the presence of retinal fluid, hyperreflective foci, outer retinal disruption and vitreomacular interface abnormalities.

 

Results

 

33 patients completed 48 weeks follow up. Ranibizumab-treated subjects gained 6.0 ETDRS letters while laser subjects lost 0.9 letters (p=0.008). FAZ area increased from baseline to 48 weeks in ranibizumab-treated subjects by 0.113 ±0.124 mm² and by 0.153 ±0.078 mm² in laser treated subjects (p=0.34). At 48 weeks, external limiting membrane was more likely to be present than interrupted in the ranibizumab group than the laser group (45% vs 0%, p=0.013). Retinal sensitivity improved in the central 4° by 3.2 dB in the ranibizumab group and by 1.9 dB in the laser group. Tritan color contrast threshold improved from 81% to 70% (ranibizumab) and from 89% to 86% (laser). PERG P50 amplitude decreased in laser-treated subjects by 10.7% at 48 weeks and remained constant for ranibizumab-treated subjects. Other electrophysiological parameters showed no significant changes.

 

Conclusions

 

This exploratory study has shown a trend towards greater improvements in visual function with ranibizumab therapy than with laser for DME, without evidence of increased macular ischemia. These findings can be used to inform the design of larger clinical trials.

 

Keywords: 499 diabetic retinopathy • 748 vascular endothelial growth factor • 688 retina