Comparison of Modified ETDRS and Mild Macular Grid Laser Photocoagulation

Strategies for Diabetic Macular Edema

Sponsored by the National Eye Institute, National Institutes of Health, U.S. Department of Health and Human Services

ObjectiveObjective Compare two laser photocoagulation techniques:

Modified ETDRS focal photocoagulation (mETDRS) to areas of edema

• Direct treatment to microaneurysms• Grid to diffuse leakage

Mild macular grid (MMG) laser technique • small mild burns throughout macula• in areas with and without edema• no direct treatment of microaneurysms

BackgroundBackground Presumed mechanism of focal photocoagulation

include Closure of microaneurysms Reduced blood flow leading to auto-regulation and reduced

edema Improved oxygenation leading to auto-regulation and reduced

edema Stimulation of biochemical processes in RPE

Would light widespread laser (mild macular grid, MMG) to the macula be effective?

Pilot clinical trial

44

Study DesignStudy Design

mETDRS N=162 Eyes MMG N=161

Randomized Clinical Trial (Pilot Study)

Major Eligibility Criteria Assessed:Major Eligibility Criteria Assessed:>18 years old

Type 1 or type 2 diabetes

Study eye meets the following criteria (subjects allowed 2 study eyes): Best corrected electronic ETDRS visual acuity score of ≥19Definite retinal thickening on clinical exam due to previously untreated DMERetinal thickness measured on OCT of 250 μm or more in the central subfield or 300 μm or more in at least 1 of the 4 inner subfieldsHad no prior laser or other treatment for DME.

• Subjects with 2 study eyes: 1 eye was randomly assigned to receive 1 treatment and 1 eye was assigned to receive the other.

Mild Macular GridMild Macular Grid

40 minutes post laser treatment

6 weeks post laser treatment

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Follow-up and Treatment ScheduleFollow-up and Treatment Schedule

3.5 Month± 2 Weeks

12 Month± 4 Weeks

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8 Month± 4 Weeks

Primary outcome: Change in OCT

Secondary Outcome: Change in visual acuity

(Method: Repeated measures least squares regression models)

Measurements by certified Evaluator• Best-corrected electronic ETDRS visual

acuity• OCT-measured retinal thickness

Macular laser photocoagulation was repeated if DME persisted and such treatment was warranted in the opinion of the investigator, according to the treatment guidelines.

Baseline Demographics and Clinical Characteristics

Baseline Demographics and Clinical Characteristics

Subject Characteristics mETDRS Group(N=162 eyes)

MMG Group (N=161 eyes)

Gender: Women - N(%) 38% 43%

Age (yrs) - Mean+SD 58+11 59+11

Race - N(%)

White 63% 64%

African-American 18% 19%

Hispanic or Latino 10% 8%

Asian 5% 4%

Other 4% 4%

Baseline Demographics and Clinical Characteristics

Baseline Demographics and Clinical Characteristics

mETDRS Group

(N=162 eyes)

MMG Group (N=161 eyes)

Diabetes Type - N(%)

Type 1 7% 6%

Type 2 93% 94%

Duration of Diabetes (years) - Mean+SD

14+9 13+8

HbA1c (%) - Mean+SD 8.2+1.9 8.2+2.1

Baseline Demographics and Clinical Characteristics Cont.

Baseline Demographics and Clinical Characteristics Cont.

Ocular Characteristics mETDRS Group

(N=162 eyes)

MMGGroup

(N=161 eyes)

E-ETDRS Visual Acuity (letter score) - N(%)

> 84: 20/20 or better 27% 20%

83-69: < 20/20 to 20/40 47% 57%

68-49: < 20/40 to 20/100 22% 17%

48-34: < 20/100 to 20/200 4% 4%

33-19: < 20/200-20/400 0% 2%

Mean+SD - letters 74+12 73+14

OCT mETDRS Group

(N=162 eyes)

MMGGroup

(N=161 eyes)

Central Subfield Thickness (microns) Mean+SD

335+128 346+118

Maximum retinal thickening of central and innersubfields (microns, see text) Mean+SD

148+122 163+111

Number of eyes with at least 1 unthickened subfield - N(%)

60% 55%

Baseline Demographics and Clinical Characteristics Cont.

Baseline Demographics and Clinical Characteristics Cont.

Mean Central Subfield ThicknessMean Central Subfield Thickness

Percent Edema Resolved for Central Subfield Thickness

P=0.29

P=0.23

P=0.56

Percent of Edema Resolved for Weighted Inner Zone ThicknessPercent of Edema Resolved for Weighted Inner Zone Thickness

Note: Weighted inner zone thickness is a weighted average of the thickness in the central and 4 inner subfields

P=0.57

P=0.02

P=0.07

Percent of Edema Resolved for Maximum Retinal Thickening

Percent of Edema Resolved for Maximum Retinal Thickening

Note: Maximum thickening is the maximum amount of excess thickness of the central and 4 inner subfields

P=0.57

P=0.26 P=0.93

Percent of Edema Resolved for Retinal Volume

Percent of Edema Resolved for Retinal Volume

Note: Retinal volume is a weighted average of the thickness in the central, 4 inner and 4 outer subfields converted to mm3

P=0.31

P=0.01 P=0.12

Percent with ≥ 10 Letter Improvement in Visual Acuity

Percent with ≥ 10 Letter Improvement in Visual Acuity

Percent with ≥ 10 Letter Worsening in Visual Acuity

Percent with ≥ 10 Letter Worsening in Visual Acuity

SummarySummary

Maximum retinal thickening in the inner zone (within 1500 microns of macular center), central subfield thickness, weighted inner zone thickness and retinal volume decreased in both groups

MMG less effective than mETDRS in reducing retinal thickening

Visual acuity similar in both groups