Evaluation of Vitrectomy for Diabetic Macular Edema (Vitrectomy-D)

• ClinicalTrials.gov Identifier: NCT00709319
• Recruitment Status: Completed
• First Posted: July 3, 2008
• Results First Posted: April 2, 2012
• Last Update Posted: October 7, 2019
• Sponsor: Jaeb Center for Health Research
• Collaborator: National Eye Institute (NEI)
• Information provided by (Responsible Party): Jaeb Center for Health Research

Study Description

Brief Summary:

The study is designed as a prospective cohort study to assess changes in visual acuity and retinal thickening and surgical complications in subjects undergoing vitrectomy for diabetic macular edema.

The study also aims to identify subgroups in which there appears to be a benefit of vitrectomy and subgroups in which vitrectomy does not appear to be beneficial and to obtain data that can be used to plan a randomized trial.

Subject will be followed through 2 years, with a primary outcome at 6 months post vitrectomy surgery. The vitrectomy procedure will be performed based on the investigators usual care and is not considered part of the research although the procedure performed will be collected.

Condition or disease
Diabetic Retinopathy; Diabetic Macular Edema

Detailed Description:

Study Design The study is designed as a prospective cohort study. A randomized trial design was considered but rejected after deciding that there was insufficient equipoise on the part of the investigator group to randomize eyes with DME and vitreal traction to surgery or no surgery (thus eyes which potentially may benefit most from vitrectomy would not be included), and there was insufficient information available on the natural course or surgical outcomes of eyes with DME but without significant traction.

A cohort study provides the opportunity to collect data prospectively using a standardized protocol to assess the potential benefits and risks of vitrectomy. The results can be used to determine whether proceeding with a randomized trial has merit and what the design of the trial should be. If a randomized trial is to be conducted, the results plus the cohort study experience can be used to help design the protocol.

Study Objectives

1. To provide information on the following outcomes in eyes with Diabetic Macular Edema (DME) that undergo vitrectomy: visual acuity, retinal thickening, resolution of traction (if present), surgical complications.
2. To identify subgroups in which there appears to be a benefit of vitrectomy and subgroups in which vitrectomy does not appear to be beneficial.
3. To obtain data that can be used to plan a randomized trial.

B. Intervention Vitrectomy performed by the investigator's usual routine.

C. Duration of Follow-Up: Two years

D. Follow-up Visit Schedule Study visits for data collection at 3 and 6 months then 1, and 2 years. Additional visits follow investigator's usual routine.

E. Rationale:

There are at least two avenues of investigation that support the theoretical value of vitrectomy for the treatment of DME, based on (1) vitrectomy for the relief of traction on the macula and (2) vitrectomy to improve oxygenation of the macula leading to decreased permeability with subsequent resolution or decrease in DME.

Vitrectomy to relieve biomechanical traction on the macula has been reported widely. Schepens and coworkers discussed the role of the vitreous and vitreomacular traction in cystoid macular edema in 1984. Nasrallah et al observed in 1988 the resolution of diabetic macular edema in individuals with spontaneous separation of the vitreous gel from the retina. In 1992, Lewis and coworkers reported success with vitrectomy and peeling of a "thickened hyaloid membrane" in eyes with DME that had this anatomical feature. Since this report of a nonrandomized retrospective case series, other authors have prospectively analyzed their series and supported the concept that relief of clear-cut anteroposterior traction, usually in the setting of an epiretinal membrane complex and associated vitreous adherence, may ameliorate macular thickening and edema in DME. Evaluation of these individuals and documentation of pre and postoperative characteristics have been rendered vastly more objective by ocular coherence tomography and the Retina Thickness Analyzer. Series using optical coherence tomography (OCT) to image cases where vitreomacular traction is observed and in some cases treated, has confirmed the clinical impression of mechanical forces at work on the posterior retina and has documented the anatomic improvement with surgery. How and in which cases OCT could refine our ability to diagnose and define clinically important anatomical features or relationships has not been investigated. As Kaiser and coworkers have documented, the OCT findings in the cases that have thus far come to vitrectomy in these situations support a conclusion that the disease process has progressed very far and in many cases the individuals have actual traction retinal detachments in their maculae. These severe cases are the exception in the spectrum of DME: most cases of macular edema have no obvious vitreomacular traction, but this factor has not been investigated adequately with our newer and more sophisticated imaging techniques. It is possible that subclinical traction on the macula exists in a large number of individuals with diabetes, whose internal limiting membranes at the vitreomacular interface often have a thickened, hypercellular appearance and whose vitreous gels, gradually contracting over many years, may exert subclinical but significant traction on the compromised diabetic macular vascular bed.

The other line of reasoning and prior research that supports the possibility that vitrectomy would help DME is that articulated by Steffanson and others indicating that posterior segment oxygenation improves after vitrectomy. Using oxygen sensors on the retinal surface, these investigators have shown that retinal oxygen tensions increase after the vitreous gel is removed and the posterior segment becomes perfused by relatively oxygen-rich aqueous humor. Supporting this conclusion is the additional observation that retinal vessels decrease in caliber after vitrectomy, presumably in response to the improvement in hypoxia, although confounding factors that could contribute to this decrease, such as the addition of endolaser retinal photocoagulation, have not been ruled out. Numerous lines of investigation have elucidated factors producing permeability in retinal blood vessels. One of the most central of these factors is Vascular Endothelial Growth factor (VEGF), formerly known as Vascular Permeability Factor (VPF). VEGF is known to be upregulated by hypoxia, and downregulated by increased oxygenation. The speculated sequence of events in which vitrectomy produces improved oxygenation of the posterior segment, leading to downregulation of VEGF, leading to decreased vasopermeability, resulting in reduced macular thickening, is a plausible one. More rapid clearing of growth factors in the vitrectomized eye has also been postulated as a potential mechanism for this response.

See full protocol at drcr.net for list of references

Study Design

• Study Type: Observational
• Actual Enrollment: 87 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Evaluation of Vitrectomy for Diabetic Macular Edema Study
• Study Start Date: July 2005
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: February 2009

Groups and Cohorts

Group/Cohort
Primary; Subjects vitreomacular traction, visual acuity 20/63 to 20/400, retinal thickness >300 microns in the central subfield on OCT, and cataract extraction not being performed in conjunction with vitrectomy.

Outcome Measures

Primary Outcome Measures :

1. Visual Acuity [ Time Frame: Baseline to 6 months ]
   Change in best correct visual acuity letter score from baseline to six months as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
2. Change in Optical Coherence Tomography Measured Central Subfield Thickness From Baseline [ Time Frame: Baseline to 6 Months ]
   Change in central subfield thickness is followup central subfield retinal thickness minus baseline thickness.
3. Percent of Participants With Change in Visual Acuity From Baseline to Six Months [ Time Frame: Baseline to 6 months ]
4. Change in Optical Coherence Tomography Central Subfield Thickness From Baseline to 6 Months [ Time Frame: Baseline to 6 months ]
   Change in thickness is followup thickness minus baseline thickness.

Secondary Outcome Measures :

1. Surgical Complications From Baseline to Six Months [ Time Frame: Baseline to 6 months ]
   Including intraoperative and perioperative medical complications. Same subject could have more than one complication

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

adults with diabetic macular edema

Criteria

Subject-level Inclusion Criteria

To be eligible, the following inclusion criteria (1-3) must be met:

1. Age >= 18 years
2. Diagnosis of diabetes mellitus (type 1 or type 2)

3. Able and willing to provide informed consent.

   Subject-level Exclusion Criteria

   A patient is not eligible if any of the following exclusion criteria (4-6) are present:

4. 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).
5. Patient is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first year of the study.
6. Blood pressure >180/110 (systolic above 180 OR diastolic above 110).

Study Eye Criteria

To be a study eye, all of the inclusion criteria (a-e) and none of the exclusion criteria (f-m) listed below must be met. A patient can have only one study eye. If both eyes are eligible and undergoing vitrectomy, the first eye having surgery will be the study eye.

The eligibility criteria for a study eye are as follows:

Inclusion

1. Vitrectomy being performed as treatment for DME.
2. E-ETDRS visual acuity 20/800 or better (E-ETDRS visual acuity score >= 3 letters).
3. Definite retinal thickening due to diabetic macular edema based on clinical exam involving the center of the macula.
4. Presence of vitreomacular traction associated with macular edema OR edema is felt to be too diffuse to respond to focal or grid laser OR edema judged to be inadequately responsive to previous treatment(s) and unlikely to benefit from further focal photocoagulation.

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

   Exclusion

6. Macular edema is considered to be due to a cause other than diabetic macular edema.
7. 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 abnormalities, subfoveal hard exudates, fibrous metaplasia, nonretinal condition).
8. 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, post-surgical cystoid macular edema, etc.).
9. History of retinal macular photocoagulation, intravitreal corticosteroids, or other treatment for DME within 3.5 months prior to enrollment.
10. History of peripheral scatter photocoagulation within 4 months prior to enrollment or anticipated need within the 4 months following enrollment.
11. History of prior pars plana vitrectomy.
12. 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 enrollment.
13. History of YAG capsulotomy performed within 2 months prior to enrollment.

Contacts and Locations

Locations

United States, California

University of California, Irvine

Irvine, California, United States, 92697

Loma Linda University Health Care, Dept. of Ophthalmology

Loma Linda, California, United States, 92354

Southern California Desert Retina Consultants, MC

Palm Springs, California, United States, 92262

West Coast Retina Medical Group, Inc.

San Francisco, California, United States, 94107

Bay Area Retina Associates

Walnut Creek, California, United States, 94598

United States, Florida

University of Florida College of Med., Department of Ophthalmology

Jacksonville, Florida, United States, 32209

Florida Retina Consultants

Lakeland, Florida, United States, 33805

Sarasota Retina Institute

Sarasota, Florida, United States, 34239

Center for Retina and Macular Disease

Winter Haven, Florida, United States, 33880

United States, Hawaii

Retina Consultants of Hawaii, Inc.

'Aiea, Hawaii, United States, 96701

Retina Associates of Hawaii, Inc.

Honolulu, Hawaii, United States, 96813

United States, Indiana

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

Indianapolis, Indiana, United States, 46290

John-Kenyon American Eye Institute

New Albany, Indiana, United States, 47150

United States, Kentucky

Paducah Retinal Center

Paducah, Kentucky, United States, 42001

United States, Maryland

Elman Retina Group, P.A.

Baltimore, Maryland, United States, 21237

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, United States, 21287-9277

Retina Consultants of Delmarva, P.A.

Salisbury, Maryland, United States, 21801

United States, Massachusetts

Joslin Diabetes Center

Boston, Massachusetts, United States, 02215

United States, Michigan

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

Detroit, Michigan, United States, 48202

Vitreo-Retinal Associates

Grand Rapids, Michigan, United States, 49525

Associated Retina Consultants

Williamsburg, Michigan, United States, 49690

United States, Minnesota

Retina Center, PA

Minneapolis, Minnesota, United States, 55404

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Missouri

Barnes Retina Institute

Saint Louis, Missouri, United States, 63110

United States, New York

Retina Consultants, PLLC

Slingerlands, New York, United States, 12159

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, United States, 13224

United States, North Carolina

Charlotte Eye Ear Nose and Throat Assoc, PA

Charlotte, North Carolina, United States, 28210

Horizon Eye Care, PA

Charlotte, North Carolina, United States, 28211

United States, Ohio

Retina Associates of Cleveland, Inc.

Beachwood, Ohio, United States, 44122

United States, Oklahoma

Dean A. McGee Eye Institute

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Retina Northwest, PC

Portland, Oregon, United States, 97210

Casey Eye Institute

Portland, Oregon, United States, 97239

United States, South Carolina

Palmetto Retina Center

Columbia, South Carolina, United States, 29169

Carolina Retina Center

Columbia, South Carolina, United States, 29223

United States, South Dakota

Black Hills Regional Eye Institute

Rapid City, South Dakota, United States, 57701

United States, Tennessee

Southeastern Retina Associates, PC

Kingsport, Tennessee, United States, 37660

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, United States, 37909

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

West Texas Retina Consultants P.A.

Abilene, Texas, United States, 79605

Retina Research Center

Austin, Texas, United States, 78705

Texas Retina Associates

Dallas, Texas, United States, 75231

Charles A. Garcia, PA & Associates

Houston, Texas, United States, 77002

Retina and Vitreous of Texas

Houston, Texas, United States, 77025

Texas Retina Associates

Lubbock, Texas, United States, 79424

Valley Retina Institute

McAllen, Texas, United States, 78503

United States, Utah

Rocky Mountain Retina Consultants

Salt Lake City, Utah, United States, 84107

United States, Washington

University of Washington Medical Center

Seattle, Washington, United States, 98195

United States, Wisconsin

University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service

Madison, Wisconsin, United States, 53705

Sponsors and Collaborators

Jaeb Center for Health Research

National Eye Institute (NEI)

Investigators

• Study Chair: Julia A. Haller, M.D.; Wills Eye Institute

More Information

Publications:

Diabetic Retinopathy Clinical Research Network Writing Committee, Haller JA, Qin H, Apte RS, Beck RR, Bressler NM, Browning DJ, Danis RP, Glassman AR, Googe JM, Kollman C, Lauer AK, Peters MA, Stockman ME. Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology. 2010 Jun;117(6):1087-1093.e3. doi: 10.1016/j.ophtha.2009.10.040. Epub 2010 Mar 17.

Flaxel CJ, Edwards AR, Aiello LP, Arrigg PG, Beck RW, Bressler NM, Bressler SB, Ferris FL 3rd, Gupta SK, Haller JA, Lazarus HS, Qin H. Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: diabetic retinopathy clinical research network. Retina. 2010 Oct;30(9):1488-95. doi: 10.1097/IAE.0b013e3181e7974f.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT00709319
• Other Study ID Numbers: NEI-125; U10EY018817-03 ( U.S. NIH Grant/Contract ); U10EY014229-07 ( U.S. NIH Grant/Contract ); U10EY014231-09 ( U.S. NIH Grant/Contract )
• First Posted: July 3, 2008
• Results First Posted: April 2, 2012
• Last Update Posted: October 7, 2019
• Last Verified: September 2019

Keywords provided by Jaeb Center for Health Research:

Diabetic retinopathy; Diabetic macular edema; dme; vitrectomy

Additional relevant MeSH terms:

Macular Edema; Retinal Diseases; Diabetic Retinopathy; Edema; Macular Degeneration; Retinal Degeneration; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases