Intravitreal Triamcinolone Acetonide Versus Laser for Diabetic Macular Edema

NCT ID: NCT00367133

Last Updated: 2016-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 840 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2008-10-31

Brief Summary

The study involves the enrollment of patients over 18 years of age with diabetic macular edema(DME). Patients with one study eye will be randomly assigned (stratified by visual acuity and prior laser) with equal probability to one of the three treatment groups:

1. Laser photocoagulation

2. 1mg intravitreal triamcinolone acetonide injection

3. 4mg intravitreal triamcinolone acetonide injection

For patients with two study eyes (both eyes eligible at the time of randomization), the right eye (stratified by visual acuity and prior laser) will be randomly assigned with equal probabilities to one of the three treatment groups listed above. The left eye will be assigned to the alternative treatment (laser or triamcinolone). If the left eye is assigned to triamcinolone, then the dose (1mg or 4 mg) will be randomly assigned to the left eye with equal probability (stratified by visual acuity and prior laser).

The study drug, triamcinolone acetonide, has been manufactured as a sterile intravitreal injectable by Allergan. Study eyes assigned to an intravitreal triamcinolone injection will receive a dose of either 1mg or 4mg. There is no indication of which treatment regimen will be better.

Patients enrolled into the study will be followed for three years and will have study visits every 4 months after receiving their assigned study treatment. In addition, standard of care post-treatment visits will be performed at 4 weeks after each intravitreal injection.

Detailed Description

Diabetic retinopathy is a major cause of visual impairment in the United States. Diabetic macular edema (DME) is a manifestation of diabetic retinopathy that produces loss of central vision. Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) estimate that after 15 years of known diabetes, the prevalence of diabetic macular edema is approximately 20% in patients with type 1 diabetes mellitus (DM), 25% in patients with type 2 DM who are taking insulin, and 14% in patients with type 2 DM who do not take insulin.

In a review of three early studies concerning the natural history of diabetic macular edema, Ferris and Patz found that 53% of 135 eyes with diabetic macular edema, presumably all involving the center of the macula, lost two or more lines of visual acuity over a two year period. In the Early Treatment Diabetic Retinopathy Study (ETDRS), 33% of 221 untreated eyes available for follow-up at the 3-year visit, all with edema involving the center of the macula at baseline, had experienced a 15 or more letter decrease in visual acuity score (equivalent to a doubling of the visual angle, e.g., 20/25 to 20/50, and termed "moderate visual acuity loss").

In the ETDRS, focal/grid photocoagulation of eyes with clinically significant macular edema (CSME) reduced the risk of moderate visual loss by approximately 50% (from 24% to 12%, three years after initiation of treatment). Therefore, 12% of treated eyes developed moderate visual loss in spite of treatment. Furthermore, approximately 40% of treated eyes that had retinal thickening involving the center of the macula at baseline still had thickening involving the center at 12 months, as did 25% of treated eyes at 36 months.

Although several treatment modalities are currently under investigation, the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation, as demonstrated by the ETDRS, and intensive glycemic control, as demonstrated by the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS). In the DCCT, intensive glucose control reduced the risk of onset of diabetic macular edema by 23% compared with conventional treatment. Long-term follow-up of patients in the DCCT show a sustained effect of intensive glucose control, with a 58% risk reduction in the development of diabetic macular edema for the DCCT patients followed in the Epidemiology of Diabetes Interventions and Complications Study.

The frequency of an unsatisfactory outcome following laser photocoagulation in some eyes with diabetic macular edema has prompted interest in other treatment modalities. One such treatment is pars plana vitrectomy. These studies suggest that vitreomacular traction, or the vitreous itself, may play a role in increased retinal vascular permeability. Removal of the vitreous or relief of mechanical traction with vitrectomy and membrane stripping may be followed by substantial resolution of macular edema and corresponding improvement in visual acuity. However, this treatment may be applicable only to a specific subset of eyes with diabetic macular edema. It also requires a complex surgical intervention with its inherent risks, recovery time, and expense. Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and antibodies targeted at vascular endothelial growth factor (VEGF) are under investigation. The use of intravitreal corticosteroids is another treatment modality that has generated recent interest.

The optimal dose of corticosteroid to maximize efficacy with minimum side effects is not known. A 4mg dose of Kenalog is principally being used in clinical practice. However, this dose has been used based on feasibility rather than scientific principles.

There is also experience using Kenalog doses of 1mg and 2mg. These doses anecdotally have been reported to reduce the macular edema. There is a rationale for using a dose lower than 4mg. Glucocorticoids bind to glucocorticoid receptors in the cell cytoplasm, and the steroid-receptor complex moves to the nucleus where it regulates gene expression. The steroid-receptor binding occurs with high affinity (low dissociation constant (Kd) which is on the order of 5 to 9 nanomolar). Complete saturation of all the receptors occurs about 20-fold higher levels, i.e., about 100-200 nanomolar. A 4mg dose of triamcinolone yields a final concentration of 7.5 millimolar, or nearly 10,000-fold more than the saturation dose. Thus, the effect of a 1mg dose may be equivalent to that of a 4mg dose, because compared to the 10,000-fold saturation, a 4-fold difference in dose is inconsequential. It is also possible that higher doses of corticosteroid could be less effective than lower doses due to down-regulation of the receptor. The steroid implant studies provide additional justification for evaluating a lower dose, a 0.5mg device which delivers only 0.5 micrograms per day has been observed to have a rapid effect in reducing macular edema.

There has been limited experience using doses greater than 4mg. Jonas' case series reported results using a 25mg dose. However, others have not been able to replicate this dose using the preparation procedure described by Jonas.

In the trial, 4mg and 1mg doses will be evaluated. The former will be used because it is the dose that is currently most commonly used in clinical practice and the latter because there is reasonable evidence for efficacy and the potential for lower risk. Although there is good reason to believe that a 1mg dose will reduce the macular edema, it is possible that the retreatment rate will be higher with this dose compared with 4mg since the latter will remain active in the eye for a longer duration than the former. Insufficient data are available to warrant evaluating a dose higher than 4mg at this time.

Conditions

Diabetic Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Standard of care group: conventional treatment consisting of focal/grid photocoagulation.

Group Type: ACTIVE_COMPARATOR

Standard of Care Group

Intervention Type: PROCEDURE

Standard of care group: conventional treatment consisting of focal/grid photocoagulation.

2

Intravitreal injection of 1mg of triamcinolone acetonide

Group Type: EXPERIMENTAL

1mg triamcinolone acetonide

Intervention Type: DRUG

Intravitreal injection of 1mg of triamcinolone acetonide at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.

3

Intravitreal injection of 4mg of triamcinolone acetonide

Group Type: EXPERIMENTAL

4mg triamcinolone acetonide

Intervention Type: DRUG

4mg intravitreal triamcinolone acetonide injection at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.

Interventions

Standard of Care Group

Standard of care group: conventional treatment consisting of focal/grid photocoagulation.

Intervention Type: PROCEDURE

1mg triamcinolone acetonide

Intravitreal injection of 1mg of triamcinolone acetonide at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.

Intervention Type: DRUG

4mg triamcinolone acetonide

4mg intravitreal triamcinolone acetonide injection at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.

Intervention Type: DRUG

Other Intervention Names

soc with laser; modified ETDRS photocoagulation; corticosteroid; corticosteroid

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years

2. Diagnosis of diabetes mellitus (type 1 or type 2)

3. Able and willing to provide informed consent.

4. Patient understands that (1) if both eyes are eligible at the time of randomization, one eye will receive intravitreal triamcinolone acetonide and one eye will receive laser, and (2) if only one eye is eligible at the time of randomization and the fellow eye develops DME later, then the fellow eye will not receive intravitreal triamcinolone acetonide if the study eye received intravitreal triamcinolone acetonide (however, if the study eye was assigned to the laser group, then the fellow eye may be treated with the 4mg dose of the study intravitreal triamcinolone acetonide formulation, provided the eye assigned to laser has not received an intravitreal injection; such an eye will not be a "study eye" but since it is receiving study drug, it will be followed for adverse effects).

Exclusion Criteria

7. History of chronic renal failure requiring dialysis or kidney transplant.

8. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control). Note: Patients 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.

9. Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at the time of study entry.

10. Known allergy to any corticosteroid or any component of the delivery vehicle.

11. History of systemic (e.g., oral, IV, IM, epidural, bursal) corticosteroids within 4 months prior to randomization or topical, rectal, or inhaled corticosteroids in current use more than 2 times per week.

12. Patient is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 3 years of the study.

13. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). Note: If blood pressure is brought below 180/110 by anti-hypertensive treatment, patient can become eligible.

Study Eye Eligibility

Inclusion

1. Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (e-ETDRS) visual acuity score of ≥ 24 letters (i.e., 20/320 or better) and ≤73 letters (i.e., 20/40 or worse).

2. Definite retinal thickening due to diabetic macular edema based on clinical exam involving the center of the macula.

3. Mean retinal thickness on two Optical Coherence Tomography (OCT) measurements ≥250 microns in the central subfield.

4. Media clarity, pupillary dilation, and patient cooperation sufficient for adequate fundus photographs.

Exclusion

5. Macular edema is considered to be due to a cause other than diabetic macular edema.

6. An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, nonretinal condition).

7. An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.)

8. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).

9. History of prior treatment with intravitreal corticosteroids.

10. History of peribulbar steroid injection within 6 months prior to randomization.

11. History of focal/grid macular photocoagulation within 15 weeks (3.5 months) prior to randomization.Note: Patients are not required to have had prior macular photocoagulation to be enrolled. If prior macular photocoagulation has been performed, the investigator should believe that the patient may possibly benefit from additional photocoagulation.

12. History of panretinal scatter photocoagulation (PRP) within 4 months prior to randomization.

13. Anticipated need for PRP in the 4 months following randomization.

14. History of prior pars plana vitrectomy.

15. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 6 months or anticipated within the next 6 months following randomization.

16. History of YAG capsulotomy performed within 2 months prior to randomization.

17. Intraocular pressure ≥25 mmHg.

18. History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma.) Note: Angle-closure glaucoma is not an exclusion. A history of ocular hypertension is not an exclusion as long as (1) intraocular pressure (IOP) is <25 mm Hg, (2) the patient is using no more than one topical glaucoma medication, (3) the most recent visual field, performed within the last 12 months, is normal (if abnormalities are present on the visual field they must be attributable to the patient's diabetic retinopathy), and (4) the optic disc does not appear glaucomatous. If the intraocular pressure is 22 to <25 mm Hg, then the above criteria for ocular hypertension eligibility must be met.

19. History of steroid-induced intraocular pressure elevation that required IOP-lowering treatment.

20. History of prior herpetic ocular infection.

21. Exam evidence of ocular toxoplasmosis.

22. Aphakia.

23. Exam evidence of pseudoexfoliation.

24. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

In patients with only one eye meeting criteria to be a study eye at the time of randomization, the fellow eye must meet the following criteria:

1. Best corrected e-ETDRS visual acuity score ≥19 letters (i.e., 20/400 or better).

2. No prior treatment with intravitreal corticosteroids.

3. Intraocular pressure < 25 mmHg.

4. No history of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma.)Note: Angle-closure glaucoma is not an exclusion. A history of ocular hypertension is not an exclusion as long as (1) intraocular pressure is <25 mmHg, (2) the patient is using no more than one topical glaucoma medication, (3) the most recent visual field, performed within the last 12 months, is normal (if abnormalities are present on the visual field they must be attributable to the patient's diabetic retinopathy), and (4) the optic disc does not appear glaucomatous. If the intraocular pressure is 22 to <25 mmHg, then the above criteria for ocular hypertension eligibility must be met.

5. No history of steroid-induced intraocular pressure elevation that required IOP-lowering treatment.

6. No exam evidence of pseudoexfoliation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

Allergan

INDUSTRY

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Ip, M.D.

Role: STUDY_CHAIR

University of Wisconsin Medical School

Locations

Jones Eye Institute/University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

SCPMG Regional Offices - Kaiser Permanente

Baldwin Park, California, United States

Retina-Vitreous Associates Medical Group

Beverly Hills, California, United States

University of California, Irvine

Irvine, California, United States

Loma Linda University Health Care, Dept. of Ophthalmology

Loma Linda, California, United States

Doheny Eye Institute

Los Angeles, California, United States

Jules Stein Eye Institute

Los Angeles, California, United States

Southern California Desert Retina Consultants, MC

Palm Springs, California, United States

West Coast Retina Medical Group, Inc.

San Francisco, California, United States

Orange County Retina Medical Group

Santa Ana, California, United States

California Retina Consultants

Santa Barbara, California, United States

Bay Area Retina Associates

Walnut Creek, California, United States

Denver Health Medical Center

Denver, Colorado, United States

Eldorado Retina Associates, P.C.

Louisville, Colorado, United States

Connecticut Retina Consultants

New Haven, Connecticut, United States

Connecticut Retina Consultants

New Haven, Connecticut, United States

Retina Group of Florida

Fort Lauderdale, Florida, United States

National Ophthalmic Research Institute

Fort Myers, Florida, United States

Central Florida Retina Institute

Lakeland, Florida, United States

Florida Retina Consultants

Lakeland, Florida, United States

Sarasota Retina Institute

Sarasota, Florida, United States

International Eye Center

Tampa, Florida, United States

Southeast Retina Center, P.C.

Augusta, Georgia, United States

Retina Associates of Hawaii, Inc.

Honolulu, Hawaii, United States

Retina Consultants of Hawaii, Inc.

‘Aiea, Hawaii, United States

Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Illinois Retina Associates

Joliet, Illinois, United States

Raj K. Maturi, M.D., P.C.

Indianapolis, Indiana, United States

John-Kenyon American Eye Institute

New Albany, Indiana, United States

Retina and Vitreous Associates of Kentucky

Lexington, Kentucky, United States

Paducah Retinal Center

Paducah, Kentucky, United States

Maine Vitreoretinal Consultants

Bangor, Maine, United States

Elman Retina Group, P.A.

Baltimore, Maryland, United States

Wilmer Ophthalmological Institute at Johns Hopkins

Baltimore, Maryland, United States

The Retina Group of Washington

Greenbelt, Maryland, United States

Retina Consultants of Delmarva, P.A.

Salisbury, Maryland, United States

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

Kresge Eye Institute

Detroit, Michigan, United States

Henry Ford Health System, Dept of Ophthalmology and Eye Care Services

Detroit, Michigan, United States

Associated Retinal Consultants

Grand Rapids, Michigan, United States

Vision Research Foundation

Royal Oak, Michigan, United States

Retina Center, PA

Minneapolis, Minnesota, United States

University of Minnesota

Minneapolis, Minnesota, United States

St. Louis University Eye Institute

St Louis, Missouri, United States

Barnes Retina Institute

St Louis, Missouri, United States

Delaware Valley Retina Associates

Lawrenceville, New Jersey, United States

The New York Eye and Ear Infirmary/Faculty Eye Practice

New York, New York, United States

University of Rochester

Rochester, New York, United States

Retina Consultants, PLLC

Slingerlands, New York, United States

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, United States

University of North Carolina, Dept. of Ophthalmology

Chapel Hill, North Carolina, United States

Charlotte Eye Ear Nose and Throat Assoc, PA

Charlotte, North Carolina, United States

Horizon Eye Care, PA

Charlotte, North Carolina, United States

Wake Forest University Eye Center

Winston-Salem, North Carolina, United States

Retina Associates of Cleveland, Inc.

Beachwood, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

OSU Eye Physicians and Surgeons, LLC.

Dublin, Ohio, United States

Dean A. McGee Eye Institute

Oklahoma City, Oklahoma, United States

Retina Northwest, PC

Portland, Oregon, United States

Casey Eye Institute

Portland, Oregon, United States

Penn State College of Medicine

Hershey, Pennsylvania, United States

University of Pennsylvania Scheie Eye Institute

Philadelphia, Pennsylvania, United States

Retina Consultants

Providence, Rhode Island, United States

Palmetto Retina Center

Columbia, South Carolina, United States

Carolina Retina Center

Columbia, South Carolina, United States

Black Hills Regional Eye Institute

Rapid City, South Dakota, United States

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

West Texas Retina Consultants P.A.

Abilene, Texas, United States

Texas Retina Associates

Arlington, Texas, United States

Retina Research Center

Austin, Texas, United States

Texas Retina Associates

Dallas, Texas, United States

University of Texas Medical Branch, Dept of Ophthalmology and Visual Sciences

Galveston, Texas, United States

Charles A. Garcia, PA & Associates

Houston, Texas, United States

Retina and Vitreous of Texas

Houston, Texas, United States

Retina Consultants of Houston, PA

Houston, Texas, United States

Texas Retina Associates

Lubbock, Texas, United States

Valley Retina Institute

McAllen, Texas, United States

Rocky Mountain Retina Consultants

Salt Lake City, Utah, United States

University of Washington Medical Center

Seattle, Washington, United States

University of Wisconsin-Madison, Dept. of Ophthalmology

Madison, Wisconsin, United States

Medical College of Wiconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Bhavsar AR, Ip MS, Glassman AR; DRCRnet and the SCORE Study Groups. The risk of endophthalmitis following intravitreal triamcinolone injection in the DRCRnet and SCORE clinical trials. Am J Ophthalmol. 2007 Sep;144(3):454-6. doi: 10.1016/j.ajo.2007.04.011.

Reference Type: RESULT

PMID: 17765429 (View on PubMed)

Ip MS, Bressler SB, Antoszyk AN, Flaxel CJ, Kim JE, Friedman SM, Qin H; Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone and focal/grid photocoagulation for diabetic macular edema: baseline features. Retina. 2008 Jul-Aug;28(7):919-30. doi: 10.1097/IAE.0b013e31818144a7.

Reference Type: RESULT

PMID: 18698292 (View on PubMed)

Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008 Sep;115(9):1447-9, 1449.e1-10. doi: 10.1016/j.ophtha.2008.06.015. Epub 2008 Jul 26.

Reference Type: RESULT

PMID: 18662829 (View on PubMed)

Diabetic Retinopathy Clinical Research Network (DRCR.net); Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, Hartnett E, Ip MS, Kim JE, Kollman C. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009 Mar;127(3):245-51. doi: 10.1001/archophthalmol.2008.610.

Reference Type: RESULT

PMID: 19273785 (View on PubMed)

Aiello LP, Edwards AR, Beck RW, Bressler NM, Davis MD, Ferris F, Glassman AR, Ip MS, Miller KM; Diabetic Retinopathy Clinical Research Network. Factors associated with improvement and worsening of visual acuity 2 years after focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2010 May;117(5):946-53. doi: 10.1016/j.ophtha.2009.10.002. Epub 2010 Feb 1.

Reference Type: RESULT

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Bressler NM, Edwards AR, Beck RW, Flaxel CJ, Glassman AR, Ip MS, Kollman C, Kuppermann BD, Stone TW; Diabetic Retinopathy Clinical Research Network. Exploratory analysis of diabetic retinopathy progression through 3 years in a randomized clinical trial that compares intravitreal triamcinolone acetonide with focal/grid photocoagulation. Arch Ophthalmol. 2009 Dec;127(12):1566-71. doi: 10.1001/archophthalmol.2009.308.

Reference Type: RESULT

PMID: 20008708 (View on PubMed)

Rittiphairoj T, Mir TA, Li T, Virgili G. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. 2020 Nov 17;11(11):CD005656. doi: 10.1002/14651858.CD005656.pub3.

Reference Type: DERIVED

PMID: 33206392 (View on PubMed)

Gangaputra S, Almukhtar T, Glassman AR, Aiello LP, Bressler N, Bressler SB, Danis RP, Davis MD; Diabetic Retinopathy Clinical Research Network. Comparison of film and digital fundus photographs in eyes of individuals with diabetes mellitus. Invest Ophthalmol Vis Sci. 2011 Aug 3;52(9):6168-73. doi: 10.1167/iovs.11-7321.

Reference Type: DERIVED

PMID: 21571677 (View on PubMed)

Other Identifiers

U10EY018817-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10EY014229-07

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10EY014231-09

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NEI-105

Identifier Type: -

Identifier Source: org_study_id