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Photobiomodulation for the Treatment of Diabetic Macular Edema

Early Phase 1
Completed
Conditions
Diabetic Retinopathy
Interventions
Device: 670nm PBM
Drug: intravitreous VEGF-inhibitors
Registration Number
NCT02457975
Lead Sponsor
Medical College of Wisconsin
Brief Summary

The current application proposes to conduct a prospective, clinical trial in diabetic subjects with diabetic macular edema (DME) to evaluate the therapeutic efficacy of 670 nm photobiomodulation on validated clinical outcome measures and anatomical changes in central macula by optical coherence tomography (OCT) and other imaging modalities. A total of 30 diabetic patients with treatment-refractory clinically significant diabetic macular edema will be included in this study and randomized into two equal groups. One eye per participant will be included to avoid exposure of both eyes to the study intervention. If both eyes are eligible, the eye with worse visual acuity will become the study eye. One group will be treated with standard-of-care (intravitreal anti-VEGF agent) injections. The photobiomodulaton (PBM) intervention group will be treated with the standard-of-care intravitreal anti-VEGF (vascular endothelial growth factor) injections and 670 nm PBM in one eye. Baseline functional and anatomic assessments will be made and anti-VEGF therapy will be administered as determined by the treating Ophthalmologist.

Detailed Description

A total of 30 diabetic patients with treatment-refractory clinically significant diabetic macular edema will be included in this study and randomized into two equal groups. One eye per participant will be included to avoid exposure of both eyes to the study intervention. If both eyes are eligible, the eye with worse visual acuity will become the study eye. One group will be treated with standard-of-care (intravitreal anti-VEGF agent) injections. The PBM intervention group will be treated with the standard-of-care intravitreal anti-VEGF injections and 670 nm PBM in one eye. Baseline functional and anatomic assessments will be made and anti-VEGF therapy will be administered as determined by the treating Ophthalmologist.

Subjects in the PBM intervention arm will be treated (in addition to standard care) with 670nm light (WARP10, Quantum, Devices, Inc, Barneveld, WI). The portable, battery-operated 670 nm LED array specifically designed not to generate heat will be hand held 1 inch from the closed treatment eye. An 80-sec light treatment will be delivered. After 80 sec a timer turns off the light. The dose of light delivered at the surface of the cornea is calculated to be 4.0 J/cm2 (80 sec x 0.05 W/cm2 = 4.0 J/cm2). PBM treatment will be applied for 80 sec once per day, three consecutive days per week for 8 weeks. Previous clinical studies, have shown this treatment regimen and dose to be safe and effective in the treatment of dry AMD and non-center involving DME.

ASSESSMENTS: Subjects will undergo a detailed functional and structural evaluation at baseline and at 8 and 24 weeks. Seven-field color fundus photographs will be obtained for ETDRS retinopathy grading at baseline 8 and 24 weeks. Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) will be obtained at every visit. Fundus fluorescein angiography and Spectralis OCT scans will be obtained according to predefined protocols. Blood pressure and glycosylated hemoglobin level will be recorded at baseline and 8 and 24 weeks to identify any changes in systemic status that could affect retinopathy grade and macular edema. Cataract status will be recorded at baseline and 8 and 24 weeks as a safety measure and as a possible confounding factor for visual acuity assessment.

OUTCOME MEASURES: Functional measure will be change in ETDRS BCVA from baseline. Structural outcome measures will include changes in qualitative and quantitative OCT parameters, including macular thickness and volume in 9 ETDRS subfields, obtained from automated measures in the Heidelberg Eye Explorer software (Heidelberg Engineering GmbH, Heidelberg, Germany) without formally correcting for boundary detection error; these measures are highly reproducible. Changes in intraretinal and subretinal fluid on OCT will be evaluated. The change in ETDRS severity grade of diabetic retinopathy will be reported from 7-field color fundus photographs. Safety parameters will include the reporting of ocular and nonocular adverse events. Changes to the greatest linear dimension and area of the foveal avascular zone on fluorescein angiography, together with the degree of perifoveal capillary loss, will be reported. The grading of photographs both for retinopathy grade and foveal avascular zone measurements will be carried out by a trained and certified senior diabetic retinopathy grader at the Medical College of Wisconsin. The number of anti-VEGF treatments in the two arms will be compared as a secondary measure of effect of PBM.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
Inclusion Criteria

Adult patients with type 1 or 2 diabetes

Exclusion Criteria

Uncontrolled glaucoma; aphasia cataract precluding fundus photography; external ocular infections; previous anti-VEGF or laser treatment in the preceding 3 months in both eyes; angiographic evidence of macular ischemia macular edema glycosylated hemoglobin of more than 11.0% past medical history of chronic renal failure an arteriothrombotic event within 6 months before randomization pregnancy or breastfeeding.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
670nm PBM plus VEGF-inhibitors670nm PBMSubjects in the 670 nm Photobiomodulation (PBM) intervention arm will be treated (in addition to Anti-VEGF treatment) with 670nm light (WARP10, Quantum, Devices, Inc, Barneveld, WI). The portable, battery-operated 670 nm LED array specifically designed not to generate heat will be held 1 inch from the closed treatment eye. A 90-sec light treatment will be delivered. After 90 sec a timer turns off the light. The dose of light delivered at the surface of the cornea is calculated to be 4.5 J/cm2 (90 sec x 0.05 W/cm2 = 4.5 J/cm2). PBM treatment will be applied for 90 sec once per day, three consecutive days per week for 8 weeks. Previous clinical studies, have shown this treatment regimen and dose to be safe and effective in the treatment of dry AMD and non-center involving DME
Intravitreous VEGF-inhibitorsintravitreous VEGF-inhibitorsThree intravitreous VEGF inhibitors - aflibercept (Eylea, Regeneron Pharmaceuticals), bevacizumab (Avastin, Genentech), and ranibizumab (Lucentis, Genentech) - are commonly used for the treatment of diabetic macular edema causing vision impairment and have been shown to be beneficial and relatively safe. Study participants in the anti-VEGF group will be treated with intravitreous injections of one of these agents: afibercept (2.0 mg), bevacizumab (1.25 mg) or ranibizumab (0.5 mg) at appropriate intervals as determined by the treating ophthalmologist.
670nm PBM plus VEGF-inhibitorsintravitreous VEGF-inhibitorsSubjects in the 670 nm Photobiomodulation (PBM) intervention arm will be treated (in addition to Anti-VEGF treatment) with 670nm light (WARP10, Quantum, Devices, Inc, Barneveld, WI). The portable, battery-operated 670 nm LED array specifically designed not to generate heat will be held 1 inch from the closed treatment eye. A 90-sec light treatment will be delivered. After 90 sec a timer turns off the light. The dose of light delivered at the surface of the cornea is calculated to be 4.5 J/cm2 (90 sec x 0.05 W/cm2 = 4.5 J/cm2). PBM treatment will be applied for 90 sec once per day, three consecutive days per week for 8 weeks. Previous clinical studies, have shown this treatment regimen and dose to be safe and effective in the treatment of dry AMD and non-center involving DME
Primary Outcome Measures
NameTimeMethod
Visual Acuity as assessed by the Early Treatment of Diabetic Retinopathy Study (EDTRS) ClassificationChange from baseline at 8 weeks; Change from baseline at 24 weeks
Secondary Outcome Measures
NameTimeMethod
Spectral Density-Optical Coherence Tomography (SD-OCT)Change from baseline at 8 weeks; Change from baseline at 24 weeks

Trial Locations

Locations (1)

Medical College of Wisconsin Froedert Hospital

🇺🇸

Milwaukee, Wisconsin, United States

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