STUDY SUBJECTS

Major inclusion criteria (Report 1):

• Adult patients with type 1 or 2 diabetes mellitus with NDPR or early PDR and/or DME in each eye, although report 1 only includes eyes with mild to moderate NPDR and DME

Major exclusion criteria (Report 1:

• Presence of high risk PDR or other significant ocular disease
• VA < 20/200

Major inclusion criteria (Report 9):

• Adult patients with type 1 or 2 diabetes mellitus with NDPR or early PDR without DME and VA >20/40 or:
• Eyes with NDPR or early PDR with DME and VA >20/200

Major exclusion criteria (Report 9):

• Presence of high risk PDR or other significant ocular disease
• Less than 5 years of follow up

RANDOMIZATION SCHEME AND INTERVENTIONS

ETDRS randomized patients to immediate photocoagulation (1/2 to PRP plus focal or immediate focal) or deferral of PRP until development of HR-PDR. Report 1 compares the deferral cohort vs the immediate focal cohort. Report 9 analyzed the rate of severe vision loss (SVL) between the cohorts.

Macular edema was defined as retinal thickening at or within 1 DD of the macular center or hard exudates in that region. Clinically significant macular edema was defined as retinal thickening at or within 1 DD of the macular center, hard exudates at or within 500 microns of the macular center if associated with retinal thickening, or a zone or zones of retinal thickening 1 DD or larger any part of which is within 1 DD of the macular center.

Treatment was done for all lesions within 2 DD of the center of the macula but at least 500 microns from the center. MAs received 50-100 micron argon burns of 0.1s duration. Lesions within 500 microns were not initially treated, but if VA was less than 20/40 and thickening persisted, lesions up to 300 microns could be treated. For areas of diffuse leakage, treatment was a grid pattern to produce light to moderate intensity, no more than 200 microns in size.

Report 9 examined eyes based on the presence or absence of macular edema as well as severe DR. Eyes without macular edema were randomized to early PRP or deferral. Eyes with DME and less severe DR were randomized to immediate focal/delayed mild PRP, immediate mild PRP/delayed focal, immediate focal/delayed full PRP, immediate full PRP/delayed focal, or deferral of laser. Eyes with DME and severe DR were randomized to immediate focal/immediate mild PRP, immediate mild PRP/delayed focal, immediate focal/immediate full PRP, immediate full PRP/delayed focal, or deferral of laser.

Retreatment was performed if eyes in the initial focal cohort developed persistent CSME at 4 month intervals. Eyes in the deferral cohort were not treated with laser initially, however after a 5 year analysis showed a benefit of focal laser, eyes initially in the deferral cohort that developed CSME received focal laser.

RESULTS (Report 1)

Visual acuity end points

• Loss of >15 letters (focal vs control): 1 year: 5% vs 8%, 1 years: 7% vs 16%, and 3 years: 12% vs 24%
• Similar results were found analyzing by baseline visual acuity and percentage of eyes with worse than 50 ETDRS letters (>20/100)
• Larger visual acuity differences were seen in patients with clinically significant macular edema
• Eyes without clinically significant macular edema at baseline had low rates of vision loss regardless of cohort

Anatomic end points

• In eyes with central retinal thickening macular edema at baseline, 35% had persistent retinal thickening at 1 year in the focal cohort compared to 63% in the deferral cohort

Adverse events

• No differences in visual field testing or color vision testing were identified between the cohorts

RESULTS (Report 9)

Visual acuity end points

• For all eyes, the 5 year rate of SVL was 3.7% in the deferral cohort and 2.6% in the early laser cohort
• Eyes with macular edema and less severe retinopathy, each strategy of early laser reduced the 5 year risk of SVL
• Immediate focal with delayed scatter was the most effective strategy for reducing the risk of moderate visual loss in eyes with DME and less severe retinopathy
• For eyes with DME and more severe retinopathy both early laser strategies reduced the risk of SVL
• In eyes with more severe DR and DME, early laser had increased moderate visual loss at the 6 week visit compared to deferral of laser, although at 1 year all early laser strategies had reduced the risk for moderate vision loss

Anatomic end points

• Early PRP reduced the rate of progression to HR-PDR in each baseline DR severity category compared to deferral of laser at 5 years

Adverse events

• Eyes with full PRP had significantly worse visual field function compared to the deferral cohort
• There were no differences in scotoma testing or color vision testing

CONCLUSIONS

• The presence of clinically significant macular edema warrants treatment with focal laser if treatable lesions are identified within 2 DD of the center of the macula on fluorescein angiography.
• In eyes with DME and PDR, immediate focal followed by delayed PRP is the strategy of choice, unless there is HR-PDR in which immediate PRP should take place.