Near-infrared Light (NIR) Therapy for Diabetic Macular Edema: A Pilot Study - Full Text View

Purpose

Summary of Study Rationale Near-infrared light (NIR) via light-emitting diodes (LED) treatment promotes retinal healing and improve visual function following high intensity laser retinal injury by augmenting cellular energy metabolism, enhances mitochondrial function, increases cytochrome C oxidase activity, stimulates antioxidant protective pathways, and promotes cell survival. LED directly benefits injured neurons in the retina, the lateral geniculate nucleus, and the visual cortex, where perception occurs. From a public health perspective, a Light-Emitting Diode (LED) Array study is important to conduct because it has been approved as a non-significant risk (NSR) device for treatment of eye disorders, it has a low cost of treatment, and it may serve as an effective, non-invasive alternative or adjunctive treatment to laser photocoagulation, the current standard of care for DME.

Study Objectives and Hypotheses

To determine the effects of short term (3 month) near-infrared light (NIR) therapy on anatomic and functional abnormalities of diabetic macular edema as assessed by visual acuity, optical coherence tomography, multifocal electroretinography (mERG) and fundus bimicroscopy.
To assess safety of short term near-infrared light therapy in eyes with diabetic macular edema.

Condition	Intervention	Phase
Diabetic Macular Edema	Device: Warp 10 LED Device Device: Near-infrared light (NIR)	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 1 Study To Determine the Effects of Short Term Near-infrared Light (NIR) Therapy on Anatomic and Functional Abnormalities of Diabetic Macular Edema, and Assess Safety of Short Term Near-infrared Light Therapy in Eyes With Diabetic Macular Edema.

Resource links provided by NLM:

Genetics Home Reference related topics: age-related macular degeneration X-linked juvenile retinoschisis

MedlinePlus related topics: Edema

U.S. FDA Resources

Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:

Excess retinal thickness on OCT at 1 month, 3 months and 6 months. goal = reduce excess thickness by at least 50% [ Time Frame: 1 month, 3 months and 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	November 2007
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Device The study will require 20 subjects. Each subject will have one "study eye" that will be designated for treatment. Subjects will be exposed to light emitted from Warp 10 LED's (Quantum Devices, Barneveld, WI) at wavelengths of 670 nm (+/-15nm) with a minimum exposure of 4 J/cm2 (4.0 - 7.68J/cm2). This is accomplished by applying the 50 mW/cm2 (50 - 80 mw/cm2) LED-generated light to the study eye. Treatments involve application of the LED-generated light for 80 seconds, twice daily. Primary efficacy and toxicity outcomes are determined by measuring excess retinal thickness via Ocular Coherence Tomography at 1 month, 3 months, and 6 months, prior to conclusion of the study. • This protocol will be stopped if, at any point in the study, a 50% increase in excess retinal thickness is demonstrated via OCT in 25% of subjects in the experimental group.	Device: Warp 10 LED Device Study Subjects will take the Warp 10 (LED) home and treat twice per day for three months Other Name: Warp 10 Device: Near-infrared light (NIR) Subjects will be exposed to light emitted from LED's at wavelengths of 670 nm (+/-15nm) with a minimum exposure of 4 J/cm2 (4.0 - 7.68J/cm2). This is accomplished by applying the 50 mW/cm2 (50 - 80 mw/cm2) LED-generated light to the study eye. Treatments involve application of the LED-generated light for 80 seconds, twice daily. Other Name: Warp 10 LED's

Arms

Assigned Interventions

Experimental: Device

The study will require 20 subjects.
Each subject will have one "study eye" that will be designated for treatment.
Subjects will be exposed to light emitted from Warp 10 LED's (Quantum Devices, Barneveld, WI) at wavelengths of 670 nm (+/-15nm) with a minimum exposure of 4 J/cm2 (4.0 - 7.68J/cm2). This is accomplished by applying the 50 mW/cm2 (50 - 80 mw/cm2) LED-generated light to the study eye.
Treatments involve application of the LED-generated light for 80 seconds, twice daily.

Primary efficacy and toxicity outcomes are determined by measuring excess retinal thickness via Ocular Coherence Tomography at 1 month, 3 months, and 6 months, prior to conclusion of the study.

• This protocol will be stopped if, at any point in the study, a 50% increase in excess retinal thickness is demonstrated via OCT in 25% of subjects in the experimental group.

Device: Warp 10 LED Device

Study Subjects will take the Warp 10 (LED) home and treat twice per day for three months

Other Name: Warp 10

Device: Near-infrared light (NIR)

Subjects will be exposed to light emitted from LED's at wavelengths of 670 nm (+/-15nm) with a minimum exposure of 4 J/cm2 (4.0 - 7.68J/cm2). This is accomplished by applying the 50 mW/cm2 (50 - 80 mw/cm2) LED-generated light to the study eye.
Treatments involve application of the LED-generated light for 80 seconds, twice daily.

Other Name: Warp 10 LED's

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age >= 18 years Subjects <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: Current regular use of insulin for the treatment of diabetes Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes Documented diabetes by ADA and/or WHO criteria (see Procedures Manual for definitions)
At least one eye meets the study eye criteria.
Fellow eye meets criteria.
Able and willing to provide informed consent.
Any candidate identified by a study investigator as being able to successfully tolerate a 3 month deferral of laser photocoagulation.

Exclusion Criteria:
Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
Subjects in poor glycemic control who, within the last 4 months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 months should not be enrolled.
Participation in an investigational trial within 30 days of NIR participation that involved treatment with any drug that has not received regulatory approval at the time of study entry.

• Note: subjects cannot receive another investigational drug while participating in the study during the first 6 months...
Major surgery within 28 days prior to participation or major surgery planned during the next 6 months.

• Major surgery is defined as a surgical procedure that is more extensive than fine needle biopsy/aspiration, placement of a central venous access device, removal/biopsy of a skin lesion, or placement of a peripheral venous catheter.
Subject is expecting to move out of the area during the 6 months of the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00846092

Contacts

Contact: Harry T Whelan, MD

414-266-7544

hwhelan@mcw.edu

Locations

United States, Wisconsin
Medical College of Wisconsin	Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Harry T Whelan, MD 414-266-7544 hwhelan@mcw.edu
Principal Investigator: Harry T Whelan, MD

Sponsors and Collaborators

Medical College of Wisconsin

The New York Eye & Ear Infirmary

Investigators

Principal Investigator:

Harry T Whelan, MD

Medical College of Wisconsin

More Information

Additional Information:

Medical College of Wisconsin Eye Institute Web Site This link exits the ClinicalTrials.gov site

Publications:

Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984 Dec;91(12):1464-74.

Moss SE, Klein R, Klein BE. Ten-year incidence of visual loss in a diabetic population. Ophthalmology. 1994 Jun;101(6):1061-70.

Moss SE, Klein R, Klein BE. The 14-year incidence of visual loss in a diabetic population. Ophthalmology. 1998 Jun;105(6):998-1003.

[No authors listed] Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):766-85.

[No authors listed] The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 Sep 30;329(14):977-86.

[No authors listed] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. Erratum in: Lancet 1999 Aug 14;354(9178):602.

[No authors listed] Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med. 2000 Feb 10;342(6):381-9. Erratum in: N Engl J Med 2000 May 4;342(18):1376.

Whelan HT, Smits RL Jr, Buchman EV, Whelan NT, Turner SG, Margolis DA, Cevenini V, Stinson H, Ignatius R, Martin T, Cwiklinski J, Philippi AF, Graf WR, Hodgson B, Gould L, Kane M, Chen G, Caviness J. Effect of NASA light-emitting diode irradiation on wound healing. J Clin Laser Med Surg. 2001 Dec;19(6):305-14. Review.

Beauvoit B, Kitai T, Chance B. Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach. Biophys J. 1994 Dec;67(6):2501-10.

Karu T. Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B. 1999 Mar;49(1):1-17. Review.

Wong-Riley MT, Liang HL, Eells JT, Chance B, Henry MM, Buchmann E, Kane M, Whelan HT. Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase. J Biol Chem. 2005 Feb 11;280(6):4761-71. Epub 2004 Nov 22.

Liang HL, Whelan HT, Eells JT, Meng H, Buchmann E, Lerch-Gaggl A, Wong-Riley M. Photobiomodulation partially rescues visual cortical neurons from cyanide-induced apoptosis. Neuroscience. 2006 May 12;139(2):639-49. Epub 2006 Feb 7.

Eells JT, Wong-Riley MT, VerHoeve J, Henry M, Buchman EV, Kane MP, Gould LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT. Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. Mitochondrion. 2004 Sep;4(5-6):559-67.

Whelan HT, Connelly JF, Hodgson BD, Barbeau L, Post AC, Bullard G, Buchmann EV, Kane M, Whelan NT, Warwick A, Margolis D. NASA light-emitting diodes for the prevention of oral mucositis in pediatric bone marrow transplant patients. J Clin Laser Med Surg. 2002 Dec;20(6):319-24.

Whelan HT, Buchmann EV, Dhokalia A, Kane MP, Whelan NT, Wong-Riley MT, Eells JT, Gould LJ, Hammamieh R, Das R, Jett M. Effect of NASA light-emitting diode irradiation on molecular changes for wound healing in diabetic mice. J Clin Laser Med Surg. 2003 Apr;21(2):67-74.

Wong-Riley MT, Bai X, Buchmann E, Whelan HT. Light-emitting diode treatment reverses the effect of TTX on cytochrome oxidase in neurons. Neuroreport. 2001 Oct 8;12(14):3033-7.

Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT. Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3439-44. Epub 2003 Mar 7.

Kowluru RA, Atasi L, Ho YS. Role of mitochondrial superoxide dismutase in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1594-9.

Kowluru RA, Kowluru V, Xiong Y, Ho YS. Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress. Free Radic Biol Med. 2006 Oct 15;41(8):1191-6. Epub 2006 Feb 6.

Nyengaard JR, Ido Y, Kilo C, Williamson JR. Interactions between hyperglycemia and hypoxia: implications for diabetic retinopathy. Diabetes. 2004 Nov;53(11):2931-8.

Obrosova IG, Stevens MJ, Lang HJ. Diabetes-induced changes in retinal NAD-redox status: pharmacological modulation and implications for pathogenesis of diabetic retinopathy. Pharmacology. 2001;62(3):172-80.

Weinberger D, Axer-Siegel R, Landau D, Yassur Y. Retinal thickness variation in the diabetic patient measured by the retinal thickness analyser. Br J Ophthalmol. 1998 Sep;82(9):1003-6.

Responsible Party:	Harry T Whelan, MD, PI, Medical College of Wisconsin
ClinicalTrials.gov Identifier:	NCT00846092 History of Changes
Other Study ID Numbers:	NIR for Diabetic Maculopathy
Study First Received:	February 16, 2009
Last Updated:	April 18, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:

Diabetic Retinopathy
Diabetic Macular Edema
NIR
Near-infrared Light Therapy

Additional relevant MeSH terms:

Edema
Macular Edema
Signs and Symptoms
Macular Degeneration

Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on September 26, 2012