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About
Although anti-vascular endothelial growth factor (VEGF) therapy is generally effective as treatment for center-involved diabetic macular edema (DME), a substantial proportion of anti-VEGF-treated eyes with DME do not achieve vision of 20/20 or complete resolution of retinal thickening. Indeed, over 50% of ranibizumab-treated eyes did not achieve a 2 or more line improvement in visual acuity from baseline at 2 years in Protocol I, a previous DRCR.net (Diabetic Retinopathy Clinical Research Network) study. Furthermore, 27% of ranibizumab-treated eyes still had central subfield (CSF) thickness on time-domain optical coherence tomography (OCT) ≥ 300 at 1 year, and more than 40% of ranibizumab-treated eyes did not achieve complete resolution of retinal thickening (< 250 microns) by 2 years. Thus, there is a need for alternative or additional treatments that will improve vision by reducing retinal edema in eyes with persistent DME following previous anti-VEGF therapy. Intravitreal steroid is not as efficacious as ranibizumab in eyes with DME overall, but it has been shown to have a positive effect for DME in some eyes and might add benefit in eyes that are already receiving anti-VEGF.
The main objective of this study is to assess the short-term effects of combination steroid+anti-VEGF therapy on visual acuity and retinal thickness on OCT in comparison with that of continued anti-VEGF therapy alone in eyes with persistent central-involved DME and visual acuity impairment despite previous anti-VEGF treatment. This study will provide important information for the design of a future confirmatory phase III clinical trial on the efficacy of combination steroid and anti-VEGF in eyes with persistent DME and vision impairment following previous anti-VEGF therapy. The primary outcome for efficacy will be the mean change in visual acuity at 24 weeks.
Each study eye is required to complete a 12-week run-in phase. The run-in phase will identify study eyes that truly have persistent DME despite anti-VEGF therapy by requiring an additional 3 injections while also collecting standardized visual acuity and OCT measurements. At the enrollment, 4-week and 8-week visits of the run-in phase, enrolled eyes will receive an intravitreal injection of ranibizumab 3mg. Then at the 12-week run-in visit, if the eye still has persistent DME, it will be randomized to receive either intravitreal sham+intravitreal ranibizumab 0.3 or intravitreal dexamethasone+intravitreal ranibizumab 0.3 injections. The randomized study duration is 24 week, during which a protocol visit takes place every month. The combination injections of sham+ranibizumab or dexamethasone +ranibizumab will be given at the randomization visit (baseline) and at the 12-week visit after randomization. In between, an intravitreal injection of ranibizumab only will be given to study eyes at the 4, 8, 16 and 20 week visits.
Enrollment
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Inclusion criteria
Age ≥ 18 years i) Individuals <18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable.
Diagnosis of diabetes mellitus (type 1 or type 2)
Any one of the following will be considered to be sufficient evidence that diabetes is present:
At least one eye meets the study eye criteria listed below.
Fellow eye (if not a study eye) meets criteria.
Able and willing to provide informed consent.
Meets all of the following ocular criteria in at least the one eye:
At least 3 injections of anti-VEGF drug (ranibizumab, bevacizumab, or aflibercept) within the prior 20 weeks.
Visual acuity letter score in study eye ≤ 78 and ≥24 (approximate Snellen equivalent 20/32 to 20/320).
On clinical exam, definite retinal thickening due to DME involving the center of the macula.
OCT CSF thickness, within 8 days of enrollment:
i) On Zeiss Cirrus ≥ 290 microns in women; ≥ 305 in men ii) On Heidelberg Spectralis: ≥ 305 microns in women; ≥ 320 in men
Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCTs.
Exclusion criteria
An individual is not eligible if any of the following exclusion criteria are present:
The following exclusions apply to the study eye only (i.e., they may be present for the non-study eye unless otherwise specified):
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129 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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