This will be a 24 month phase IV, randomised, prospective, multicentre, clinical trial of laser therapy to areas of peripheral retinal ischaemia combined with intravitreal aflibercept versus intravitreal aflibercept monotherapy. Both arms will have 2mg intravitreal aflibercept according to a treat and extend protocol. The specific aim of the study is to test whether laser therapy of peripheral retinal ischaemia reduces the overall number of intravitreal aflibercept injections required to control DMO over a 24 month period.
Diabetic retinopathy is the most common cause of blindness in individuals between the ages of 20 and 65 years in developed countries. Swelling of the central retina, or "macular oedema", is the commonest cause of visual loss in diabetic retinopathy. Recent studies have suggested peripheral retinal ischaemia contributes to macula oedema in diabetes and retinal vein occlusions. Intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy, such as Aflibercept (Eylea) has shown encouraging results in managing Diabetic Macular Oedema (DMO). There is evidence that regular treatment with anti-VEGF drugs reduces DMO and improves vision on average. Previous research at this institution has shown that an average of between 7 and 11 injections are required in the first year to stabilise the disease. However, there is a significant burden to patients in terms of frequent visits to the eye specialist, time off work and repeated injections into the eye. The purpose of this study is to see whether targeted peripheral retinal laser therapy to areas of the retina with impaired blood supply can reduce the number of intravitreal aflibercept injections required over 2 years to stabilise DMO.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
48
Aflibercept is a soluble decoy receptor and is produced by fusing all-human DNA sequences of the second immunoglobulin (Ig) domain of human VEGF receptor (VEGFR) 1 to the third Ig domain of human VEGFR-2, which are then fused to the Fc region of human IgG-1. By binding to VEGF-A, aflibercept prevents activation of the native VEGF receptors, VEGFR-1 and VEGFR-2. The study sites will be supplied by Bayer with aflibercept. Intravitreal injection of 2mg in 0.05 ml aflibercept will be administered to the study eye, according to a pre-defined treat and extend regimen.
In the experimental group, targeted laser photocoagulation will be applied to areas of peripheral retinal ischaemia 1 month after the initial intravitreal aflibercept. The trial design allows another session of targeted laser photocoagulation 1 month later to complete the treatment if required. Wide-field photography is planned at 3 months to determine if further targeted laser photocoagulation is required, and if so a third session can be applied. The laser settings are based on those used in current clinical practice and have been prospectively defined in the protocol.
Save Sight Institute
Sydney, New South Wales, Australia
Centre for Eye Research Australia
Melbourne, Victoria, Australia
Number of intravitreal aflibercept injections over 24 months
Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months
Time frame: 24 months
Number of intravitreal aflibercept injections over 12 months
Number of intravitreal aflibercept injections in each of the 2 groups required over 12 months
Time frame: 12 months
Proportion of eyes that have central macular thickness <300 microns at 12 months
Time frame: 12 months
Mean change in central macular thickness (CMT) as measured by OCT at 12 months
Time frame: 12 months
Mean change in best corrected visual acuity
Mean change in best corrected visual acuity at 12 months
Time frame: 12 months
Any change in best corrected visual acuity at 12 months
Any change in best corrected visual acuity at 12 months
Time frame: 12 months
Effect of peripheral retinal ischaemia on number of aflibercept injections
Correlation between area of peripheral retinal ischaemia and number of intravitreal injections required at 12 months
Time frame: 12 months
Disc vessel measurement
Change in disc vessel diameter at 12 months
Time frame: 12 months
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Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months
Time frame: 24 months
Proportion of eyes that have central macular thickness <300 microns at 24 months
Time frame: 24 months
Mean change in central macular thickness (CMT) as measured by OCT at 24 months
Time frame: 24 months
Mean change in best corrected visual acuity
Mean change in best corrected visual acuity at 24 months
Time frame: 24 months
Any change in best corrected visual acuity at 24 months
Any change in best corrected visual acuity at 24 months
Time frame: 24 months
Effect of peripheral retinal ischaemia on number of aflibercept injections
Correlation between area of peripheral retinal ischaemia and number of intravitreal injections required at 24 months
Time frame: 24 months
Disc vessel measurement
Change in disc vessel diameter at 24 months
Time frame: 24 months
Time until vision stabilisation
Length of time from baseline to vision stabilisation
Time frame: 24 months
Quality of life assessment
Quality of life assessment using IVI and NEI VFQ-25 forms at 24 months
Time frame: 24 months
Change in area of macular hard exudates
Change in area of macular hard exudates from baseline to 24 months
Time frame: 24 months
Change in distance of closest hard exudate from the foveal centre
Change in distance of closest hard exudate from the foveal centre between baseline and 24 months
Time frame: 24 months
Mean change in treatment interval over time
Mean change in treatment interval between intravitreal aflibercept injections over time
Time frame: 24 months