1. Volume 122, Issue 3, Pages 545-554 (March 2015)
Treatment of Diabetic Macular Edema with an Inhibitor of Vascular Endothelial-Protein Tyrosine Phosphatase That Activates Tie2 
Peter A. Campochiaro, MD, Raafay Sophie, MD, Michael Tolentino, MD, Daniel M. Miller, MD, PhD, David Browning, MD, David S. Boyer, MD, Jeffrey S. Heier, MD, Laura Gambino, BS, Barbara Withers, PhD, Mitchell Brigell, PhD, Kevin Peters, MD 
Ophthalmology 
Volume 122, Issue 3, Pages (March 2015)
DOI: /j.ophtha
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

2. Figure 3
Graph showing mean plasma levels of AKB-9778 over time after a subcutaneous injection. On day 14, plasma levels of AKB-9778 were measured at 0.25, 1, 2, and 4 hours after subcutaneous injection of AKB-9778 in each cohort (n = 6). There was a dose-dependent increase in mean AKB-9778 levels that peaked at or before 1 hour and then decreased to low levels by 4 hours after injection. BID = twice daily.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

3. Figure 4
Graphs showing the change from baseline in study eye best-corrected visual acuity (BCVA) at 7, 14, 21, and 28 days of treatment with subcutaneous AKB-9778 for each dose level. Each colored line represents data from a single patient. The asterisk on day 21 in the 5-mg twice daily cohort indicates rescue in a subject that occurred in the contralateral fellow eye; this subject is further represented in Figure 6.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

4. Figure 5
Graphs showing the change from baseline in study eye central subfield thickness (CST) at 7, 14, 21, and 28 days of treatment with subcutaneous AKB-9778 for each dose level. Each colored line represents data from a single patient. The asterisk on day 21 in the 5-mg twice-daily (BID) cohort indicates rescue in a subject that occurred in the contralateral fellow eye; more details regarding this subject are shown in Figure 6.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

5. Figure 6
Graph showing the correlation between improvement from baseline best-corrected visual acuity (BCVA) and reduction from baseline central subfield thickness (CST) at day 28. BID = twice daily.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

6. Figure 7
Horizontal spectral domain-optical coherence tomography (SD OCT) scans through the fovea of the study eye at weeks 1, 2, 3, and 4 for 7 patients in cohorts 2 through 4 who showed substantial reductions in edema. Horizontal scans through the fovea at baseline (BL), and weeks 1 through 4 after BL (W1, W2, W3, and W4) are shown for the 7 patients who received AKB-9778 of 15 mg or more and had 50-μm or more reductions in central subfield thickness (CST): (A–D) 4 patients received 15 mg AKB-9778 twice daily, (E) 1 patient received 22.5 mg twice daily, and (F, G) 2 patients received 30 mg twice daily. In panels in the top row, the best-corrected visual acuity (VA) at baseline (day 1 [D1]) in Early Treatment Diabetic Retinopathy Study letter score is shown in the top left and the baseline foveal thickness (CST) measured by optical coherence tomography is in the upper right. In the panels in rows 2 through 5, the change from baseline VA letter score (ΔVA) is shown on the left and the change from baseline foveal thickness (ΔCST) in micrometers is shown on the right. Some patients showed severe edema at baseline that was reduced gradually and almost completely eliminated by week 4, accompanied by large improvements in VA (A, C, E, G). Other patients showed substantial improvements in edema and BCVA, but still had residual edema at week 4 (D, F). One patient (B), who had very severe macular edema at baseline with a large fluid-filled cavity in the center of the fovea, had a large reduction of 185 μm in foveal thickness, but still had severe edema and a moderate fluid-filled cavity in the fovea and no improvement in BCVA at the end of the 4-week dosing period.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions

7. Figure 8
Horizontal optical coherence tomography (OCT) scans through the fovea at all time points during treatment with AKB mg twice daily. A patient with severe macular edema in both eyes despite multiple vascular endothelial growth factor-binding protein injections in each eye was enrolled in the 5-mg twice-daily cohort. At day 1 (D1), week 1 (W1), W2, and W3, there was severe macular edema (central subfield thickness [CST]) in both eyes; therefore at W3, the investigator performed rescue therapy in the fellow eye (injection of 0.5 mg ranibizumab). At W4, there was resolution of edema in the fellow eye, but there was also a substantial reduction of edema and improvement in visual acuity (VA) in the study eye. At the week 6 visit, the edema in the study eye was worse; an injection of 0.5 mg ranibizumab was given and there was resolution of edema at week 8 and mild recurrent intraretinal fluid at week 12. There was prolonged benefit in the fellow eye after the ranibizumab injection at week 3. ΔCST = change from baseline foveal thickness; ΔVA = change from baseline visual acuity letter score.
Ophthalmology  , DOI: ( /j.ophtha )
Copyright © 2015 American Academy of Ophthalmology Terms and Conditions