A Pilot Study of Laser Photocoagulation for Diabetic Macular Edema

This pilot study is not designed for hypothesis testing, but rather for hypothesis generation, for gathering outcome data, and for standardization of network protocols.

Diabetic retinopathy is a disorder of major public health importance, accounting for the majority of visual loss among working age Americans. 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 The Early Treatment Diabetic Retinopathy Study (ETDRS) showed that moderate vision loss, defined as a doubling of the visual angle (e.g., 20/20 reduced to 20/40), can be reduced by 50% or more by focal/grid laser photocoagulation according to ETDRS protocol. Although several treatment modalities are currently under investigation, the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are ETDRS 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.

In brief, the study protocol involves the enrollment of patients >=18 years of age who have DME involving or threatening the center of the macula and who have not had prior focal/grid laser photocoagulation for DME. These are patients for whom the standard of care would be to treat with laser photocoagulation. Eligible eyes will be randomly assigned to receive either the modified-ETDRS technique or the MMG technique. Outcome assessments will include Optical Coherence Tomography (OCT), fundus photography, fluorescein angiography and standardized best-corrected visual acuity.

The study consists of two phases: Phase 1 (the primary study), which consists of the first 12 months of follow up, during which a structured protocol is followed; and Phase 2, which consists of the second and third years of follow up, during which the management of DME can include techniques other than laser photocoagulation, at discretion of the investigator.

During Phase 1, follow-up visits will occur at 15 weeks (3.5 months) ±14 days, 34 weeks (8 months) ±28 days, and 52 weeks (12 months) ±28 days. The primary outcome for phase 1 is at 12 months. The primary study objectives of Phase 1 include:

• Develop standardized study procedures for future DME studies
• Obtain outcome data (e.g. changes in retinal thickness, area of retinal thickening, area of hard exudate, need for retreatment, onset of new areas of DME and changes in visual acuity) following use of the modified-ETDRS photocoagulation technique for patients with DME and various levels of retinopathy severity.
• Collect pilot data using the MMG technique to determine whether a subsequent large scale definitive trial should be conducted

• Protocol visits will occur at 2 years ±8 weeks and 3 years ±8 weeks.

1. Evaluation of retreatment rates in patients who responded to laser such that no additional treatment was required at 12 months. This is a long term analysis on a “pure” group of patients and will provide important information on the DME recurrence rate and need for retreatment in study eyes of those patients whose DME improved with either of the two protocol-specified treatments received in Phase 1 such that further treatment was not necessary at the 12-month visit.
2. Provide long-term safety data for MMG. This is important due to the less well studied nature of MMG, especially over the long term.
3. Provide long-term outcome data on current standard treatment (modified ETDRS laser) in today’s patient populations to assist in powering future studies that will require at least 3 years of follow up.

Age >=18 years

• Patients <18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable.

1. 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:
     1. Current regular use of insulin for the treatment of diabetes
     2. Current regular use of oral antihyperglycemia agents for the treatment of diabetes
     3. Documented diabetes by ADA guidelines (see DRCR.net Procedures Manual)
2. No history of renal failure requiring dialysis or renal transplant.
3. No 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;
   • Patients in poor glycemic control who recently initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 3 months should not be enrolled.
4. Ability and willingness to provide informed consent.
   No expectation that subject will be moving out of the area of the clinical center to an area not covered by another clinical center during the next 12 months.

1. Best corrected ETDRS visual acuity score =19 letters (approximately 20/400 or better).
2. Definite retinal thickening due to diabetic macular edema based on clinical exam at or within 500 microns of the macular center for which the investigator believes laser photocoagulation is indicated.
3. A thickness of 250 microns or more in the central subfield OR a thickness of 300 microns or more in any one of the four subfields directly adjacent to the central subfield on OCT.
4. No prior focal/grid laser photocoagulation in the macula.
5. No prior medical treatment for DME (e.g., intravitreal/peribulbar steroids).
6. No panretinal scatter photocoagulation (PRP) within prior 4 months.
7. No anticipated need for PRP within next 4 months.
8. No major ocular surgery (including cataract extraction, any other intraocular surgery, scleral buckle, glaucoma filter, cornea transplant, etc.) within prior 6 months.
9. No Nd:YAG laser capsulotomy within prior 2 months.
10. Macular edema is not considered to be due to a cause other than diabetic macular edema
    • An eye should not be considered eligible (1) if the macular edema is considered to be related to cataract extraction or (2) clinical exam and/or OCT suggests that vitreoretinal interface disease (eg. vitreo-retinal traction or epriretinal membrane) is the primary cause of the macular edema.
      
11. Media clarity, pupillary dilation, and patient cooperation sufficient for adequate fundus photos.
12. No ocular condition (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the first 12 months of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome).
    • Glaucoma per se is not an exclusion.

No longer recruiting. Comments: Recruitment has ended.

Completed, with results published. Comments:

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