Bird China AF and CNV 2009.ppt

1、Treatment of CNV,Disable of new vessels but not RPE Physical treatment has been disappointing New treatments based on biological approach,RAP PEDF/VEGF CNV,Neovascularisation,Macugen treatment effect continues for 2 Years,45% Benefit, P0.01,Year One,Year Two,Macugen Standard treatment,CNV in AMD,For

2、mation of lipofuscin in RPE,A2E forms in OS OS shedding Phagocytosis Degradation of phagosome Formation of residual body,Integrity of RPE in CNV Samantha Dandekar - Veronica Vaclavik, Stella Vujosevic,Autofluoresence: presence of RPE presence of PRCs No Autofluorescence: absence of RPE absence of PR

3、Cs Correlation: visual acuity length of symptoms,pt 1139388 RE ped/occ ? LE drusens,VA 1/30 12 months,pt 1146023 RE classic,VA 6/36 5 weeks,pt 132676 LE min class RE drusens,VA 6/24 6 weeks,pt 1088110 RE classic LE drusens,VA 6/36 16 weeks,pt 1133278 LE classic,VA 6/36 36 weeks,pt 1138841 LE occult

4、?,VA 6/24 20 months,Subfoveal CNV: integrity of AF at Fovea: 0.79 RPE intact in 54 of 79 eyes with symptoms of less that 20 months,Type of CNV Classicminimally occultP:Fisher exact classic Intact27 (40%) 8 (15%) 19 (35%) 0.794 Not intact13 (52%) 2 (8%) 10 (40%) Size, vision and length of symptoms in

5、 months: median (range) IntactNot intactP: Rank-sum test Lesion size mm27.0(1.1-21.6)11.7 (3.5-23.3) 0.0116 VA logmar0.54 (0-1.8)0.78 (0.3-1.8) 0.0002 Symptoms4 (0.5-20) 6 (1-18) 0.0491,Integrity of RPE in CNV,Cannot be assumed from visual acuity, lesion size, type of CNV or length of symptoms. RPE

6、/ PRCs not irretrievably lost prior to treatment Improvement of VA a reasonable expectation,Secondary Endpoint:Mean Change in Visual Acuity Over Time,17.7 letter benefit *,17.0 letter benefit *,* P 0.0001,Visit (months),-10,-8,-6,-4,-2,0,2,4,6,8,10,ETDRS letters,Sham (n=238),Ranibizumab 0.3 mg (n=23

7、8),Ranibizumab 0.5 mg (n=240),-10.5,+6.5,+7.2,Biological treatment of CNV,With good case selection results would be better In all trials AF imaging should be included in protocol Good prognosis with continuous AF remains to be proven Trials to-date have not used AF imaging,In 128 eyes of 128 patient

8、s 79 females, 49 males Mean an age 76 years Classic CNV 27 Occult CNV 59 PED 42,Heimes B, Lommatzsch A, Zeimer M, Gutfleisch M, Spital G, Bird A, Pauleikhoff D,Prediction of visual response to anti-VEGF agents,Prediction of visual response to anti-VEGF agents,Initial VA Microperimetric sensitivity O

9、CT thickness and thinning Autofluorescence,0.2 0.4 0.6 0.8 1.0,0 4 8 12 weeks,VA logMar,Group 1 Group 2 Group 3 Group 4,Treatment of CNV Grouped according to response,0.2 0.4 0.6 0.8 1.0,0 12 24 36 48 weeks,VA logMar,Group 1 Group 2 Group 3 Group 4,Treatment of CNV Grouped according to response,Trea

10、tment of CNV OCT responses 12 weeks,Pre-injection Post injection,100 75 50 25 0,percemtage total,PED Occult Classic,Treatment of CNV Responses / lesion type 12 weeks,Treatment of CNV Responses / Autofluorescence 12 weeks,Anti VEGF agents best to-date effective and safe Is Lucentis as good as can be

11、achieved? What visual outcome could be expected with better case selection?,CNV current treatment,10 months VA 6/9,3 months later decrease VA 6/24,8 Months VA 6/18,4 months later VA 6/60,Biological treatment of CNV,Why is VA poor with intact AF? Why does VA improve with anti-VEGF treatment,Effects o

12、f VEGF on RPE polarisation,Ablonczy Z and Crosson CE. Exp Eye Res 2007; 85:762-77,VEGF added to apical and basolateral domains Retistance measured,Effects of VEGF on RPE polarisation,Ablonczy Z and Crosson CE. Exp Eye Res 2007; 85:762-77,Change in resistance of RPE when exposed to VEGF165 10 ng/ml,N

13、ormalised resistance,Normalised resistance,Effects of VEGF on RPE polarisation,Ablonczy Z and Crosson CE. Exp Eye Res 2007; 85:762-77,35% increase in outward inulin diffusion VEGF-R2 receptors restricted to apical domain Effect blocked by VEGF-R2 blockade Resistance of cultures low No investigation of polar epitopes,RPE a polar system,Polar distribution of proteins Electrical resistance 400 ohms / sq. cm.,RPE function,Outward movement of ions/water Homeostasis of outer retina extra-cellular space Directional transport of metabolites Pha