Are Network Results Regarding Ocular Coherence Tomography (OCT) Relevant to Clinical Practice and Clinical Trials? Sponsored by the National Eye Institute, National Institutes of Health, U.S. Department of Health and Human Services. 1

2 Comparison of CPT & VA at Baseline (A) OCT CPT (Microns) VA (Letter Score ) Correlation: r = 0.52, N = 251 (20/25) (20/63) (20/160) (20/400)

3 Comparison of CPT & VA at Baseline (A) OCT CPT (Microns) VA (Letter Score ) Correlation: r = 0.52, N = 251 (20/25) (20/63) (20/160) (20/400)

4 Comparison of CPT & VA at Baseline (A) OCT CPT (Microns) VA (Letter Score ) Correlation: r = 0.52, N = 251 (20/25) (20/63) (20/160) (20/400)

5 Comparison of Change in OCT CPT and Change in VA from Baseline to 3.5 Months Absolute Change in OCT CPT (Microns) Change in VA (Letter Score) Correlation: r = 0.44, N = 185 Thicker / Visual Acuity Better (Paradoxical Change) Thinner / Visual Acuity Worse (Paradoxical Change) Thicker / Visual Acuity Worse Thinner / Visual Acuity Better

6 Comparison of Change in OCT CPT and Change in VA from Baseline to 3.5 Months Absolute Change in OCT CPT (Microns) Change in VA (Letter Score) Correlation: r = 0.44, N = 185 Thicker / Visual Acuity Better (Paradoxical Change) Thinner / Visual Acuity Worse (Paradoxical Change) Thicker / Visual Acuity Worse Thinner / Visual Acuity Better

7 Summary  There is a modest correlation of OCT measured CPT with VA in eyes with diabetic macular edema (DME)  There is a wide range of visual acuities for a given CPT  There is a modest correlation of changes in retinal thickening and VA after focal laser treatment for DME  OCT measurement alone may not be a good surrogate for VA as a primary outcome in studies of DME Diabetic Retinopathy Clinical Research Network. Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. Ophthalmology 2007;114;525-36

Other OCT Findings 8

A ‘Real’ Change in Thickness OCT Diurnal Variation Study (C) 9 Half-Width 95% C.I. Total<200μ200- <250μ 250- <400μ ≥400 μ Microns % Change11%10% 13%

Summary 10  Change in central subfield thickness exceeding 11% is likely to be real  Replicate measurements of central subfield differ by a median of 2% in patients with DME  Retinal thickness reproducibility in microns varies according to the degree of thickness Diabetic Clinical Retinopathy Clinical Research Network. Reproducibility of macular thickness and volume using Zeiss optical coherence tomography in patients with diabetic macular edema. Ophthalmology 2007;114:1520-5

11 Scans Sent to Reading Center 0%20%40%60%80%100% Error Rate 0% 2% 4% 6% 8% 10% 12% 14% 16% Never Send SD >= 3% SD >= 5% SD >= 9% SD >= 10% SD >= 7% Relationship of Error Rate by Scan Proportion Sent to RC Based on Center Point SD

Summary 12  In DME trials, error involved with automated OCT CPT measurement is sufficiently small that results are not likely to be affected if scans are not routinely sent a reading center  Greater degree of accuracy requires sending only about 1/3 of scans to the RC for assessment.

Mean Retinal Thickness According to Gender in Diabetic Subjects with Minimal or No Retinopathy (G) 13 Overall (N=97) Women (N=48) Men (N=49) P value Center Point 166µ159µ174µ<0.001 Central Subfield 201µ194µ209µ<0.001 Volume6.8mm mm mm

Mean Retinal Thickness [Minimal or No Retinopathy (G)] Women (N= 48)Men (N=49) Inner Zone (Mean + SD) Superior Nasal Inferior Temporal Outer Zone (Mean + SD) Superior Nasal Inferior Temporal

Summary 15   OCT measured thickness in diabetic subjects without retinopathy are similar to central subfields OCT data in non-diabetic subjects   The nasal inner and outer zones are thicker than the temporal inner and outer zones

Summary 16   The average central subfield is thicker in men than women.   Gender differences are large enough to consider separate norms by gender when designing clinical trials evaluating DME based on OCT Retinal thickness on Stratus™ optical coherence tomography in people with diabetes and minimal or no diabetic retinopathy. Am J Ophthalmol 2008 May;145(5):