Pilot Study of Laser Photocoagulation Therapy for Diabetic Macular Edema

The Diabetic Retinopathy Clinical Research Network (DRCRnet) was formed to conduct clinical
trials and epidemiological studies for diabetic retinopathy.

As part of the establishment of the network, it is necessary to standardize data collection
methods, testing procedures, and treatment techniques for use in the anticipated multiple
protocols to be conducted by the network. One of the treatment techniques requiring
standardization is laser photocoagulation treatment of diabetic macular edema. To accomplish
this goal, a protocol has been developed to enroll patients with diabetic macular edema who
require laser treatment. Procedures to be conducted by standardized protocols include
refraction, visual acuity testing, fundus photography, fluorescein angiography, optical
coherence tomography (OCT) and laser photocoagulation. One of the benefits from having a
structured protocol will be that the outcome data using the standardized techniques can be
used for sample size estimations in future protocols. This is particularly true for OCT for
which we need to develop standard methods to assess changes in groups of patients and for
which there are limited longitudinal data, especially in groups of patients.

The conduct of this study provides the opportunity not only to collect data on a
standardized laser protocol commonly used in current clinical practice but also to collect
pilot data evaluating a new laser technique. The 'current practice' laser protocol, modified
from the ETDRS treatment protocol, involves focal/grid photocoagulation to areas of macular
thickening with leaking MA, diffuse leakage or nonperfusion (modified-ETDRS technique).
There is extensive evidence supporting the efficacy of ETDRS laser photocoagulation
technique for the treatment of macular edema. The alternative technique, called mild macular
grid (MMG) photocoagulation, provides mild grid treatment using small, widely separated
burns to the retina from 500 to 3000 microns (3500 microns temporally) from the macular
center. This technique may potentially have fewer side effects, different edema resolution
rate or prevention of future development of macular edema as discussed below. The study will
use randomization to assign each patient to receive one of the two treatment methods.

For this protocol, participation will be open to all clinical sites that have the requisite
equipment needed for the study and to all ophthalmologists who meet criteria to be a
DRCR.net investigator. The sample size for the study will be dictated by the number of
participating sites, with each site limited to the enrollment of a maximum of four patients
or one patient per certified investigator, whichever is greater.

- INCLUSION AND EXCLUSION CRITERIA - SUBJECT-LEVEL:

1. Age greater than or equal to 18 years.

2. 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.

3. No history of renal failure requiring dialysis or renal transplant.

4. 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.

5. Ability and willingness to provide informed consent.

6. 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.

INCLUSION AND EXCLUSION CRITERIA - STUDY EYE:

At least one eye must meet all of the following criteria:

1. Best corrected ETDRS visual acuity score greater than or equal to 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, papillary 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.

A patient may have two "study eyes" only if both are eligible at the time of
randomization. An eye that becomes eligible after randomization will not be considered a
study eye for purposes of data analyses or treatment decisions although information is
being gathered on all eyes.