Clinical trial NCT00709319: Evaluation of Vitrectomy for Diabetic Macular Edema
Official title: Evaluation of Vitrectomy for Diabetic Macular Edema Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetic Retinopathy
Diabetic Macular Edema
Keywords: Diabetic retinopathy
Diabetic macular edema
dme
vitrectomy
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
First posted: 2008-07-03
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: adults with diabetic macular edema

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.

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

Eligibility 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.

Primary outcomes:
measure: Visual Acuity
timeFrame: Baseline to 6 months
measure: Change in Optical Coherence Tomography Measured Central Subfield Thickness From Baseline
timeFrame: Baseline to 6 Months
measure: Percent of Participants With Change in Visual Acuity From Baseline to Six Months
timeFrame: Baseline to 6 months
measure: Change in Optical Coherence Tomography Central Subfield Thickness From Baseline to 6 Months
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Surgical Complications From Baseline to Six Months
timeFrame: Baseline to 6 months
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care, Dept. of Ophthalmology
state: California
city: Palm Springs
country: United States
facility: Southern California Desert Retina Consultants, MC
state: California
city: San Francisco
country: United States
facility: West Coast Retina Medical Group, Inc.
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Jacksonville
country: United States
facility: University of Florida College of Med., Department of Ophthalmology
state: Florida
city: Lakeland
country: United States
facility: Florida Retina Consultants
state: Florida
city: Sarasota
country: United States
facility: Sarasota Retina Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: 'Aiea
country: United States
facility: Retina Consultants of Hawaii, Inc.
state: Hawaii
city: Honolulu
country: United States
facility: Retina Associates of Hawaii, Inc.
state: Hawaii
city: Indianapolis
country: United States
facility: Raj K. Maturi, M.D., P.C.
state: Indiana
city: New Albany
country: United States
facility: John-Kenyon American Eye Institute
state: Indiana
city: Paducah
country: United States
facility: Paducah Retinal Center
state: Kentucky
city: Baltimore
country: United States
facility: Elman Retina Group, P.A.
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute at Johns Hopkins
state: Maryland
city: Salisbury
country: United States
facility: Retina Consultants of Delmarva, P.A.
state: Maryland
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
state: Michigan
city: Grand Rapids
country: United States
facility: Vitreo-Retinal Associates
state: Michigan
city: Williamsburg
country: United States
facility: Associated Retina Consultants
state: Michigan
city: Minneapolis
country: United States
facility: Retina Center, PA
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Barnes Retina Institute
state: Missouri
city: Slingerlands
country: United States
facility: Retina Consultants, PLLC
state: New York
city: Syracuse
country: United States
facility: Retina-Vitreous Surgeons of Central New York, PC
state: New York
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose and Throat Assoc, PA
state: North Carolina
city: Charlotte
country: United States
facility: Horizon Eye Care, PA
state: North Carolina
city: Beachwood
country: United States
facility: Retina Associates of Cleveland, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Dean A. McGee Eye Institute
state: Oklahoma
city: Portland
country: United States
facility: Retina Northwest, PC
state: Oregon
city: Portland
country: United States
facility: Casey Eye Institute
state: Oregon
city: Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Columbia
country: United States
facility: Carolina Retina Center
state: South Carolina
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Kingsport
country: United States
facility: Southeastern Retina Associates, PC
state: Tennessee
city: Knoxville
country: United States
facility: Southeastern Retina Associates, P.C.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Abilene
country: United States
facility: West Texas Retina Consultants P.A.
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: Houston
country: United States
facility: Charles A. Garcia, PA & Associates
state: Texas
city: Houston
country: United States
facility: Retina and Vitreous of Texas
state: Texas
city: Lubbock
country: United States
facility: Texas Retina Associates
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina Consultants
state: Utah
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service
state: Wisconsin
Study officials:
affiliation: Wills Eye Institute
name: Julia A. Haller, M.D.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.