Augustin treatment with respect to the percentage of patients with <3 line loss of logMAR visual acuity. The largest difference between the two treatment groups at 12 and 24 months was 3.5 letters which is not clinically significant. However, the drug did not meet the primary endpoint, which led to a further evaluation of the study. This led to interesting results regarding the reflux problem and treatment intervals which had a significant impact on the data. The primary endpoint would have been met with the statistical evaluation being performed with data from predominantly classic lesions only, which is the only lesion composition of the study population. This issue is extensively discussed by Slakter and coworkers (2006). Furthermore, in a subsequent pharmacokinetic study, C- 02-47, investigators looked at correlations between drug reflux and plasma levels of anecortave acetate and showed that there was a 4-fold lower plasma level of the drug in the eyes that experienced reflux. When considering only those patients that did not have reflux in the C-01-99 study, the percentage of patients in whom vision was preserved increased from 45% to 50%. When data from patients who experienced reflux and re- treatment after 6-months were excluded, 57% of anecortave acetate 15 mg-treated patients had preserved vision. In this study it was noted that the degree of preservation of vision for both anecortave acetate 15 mg (45% with <3- line vision loss) and PDT was considerably less than previously observed in other trials including C-98-03 and the TAP study. Analysis of baseline data reveals that the lesions in this study were significantly smaller and younger at baseline than those in previous studies and included a high proportion of lesions with a retinal angiomatous proliferation (RAP) component. The high incidence of characteristics such as RAP, extensive subretinal hemorrhage/fluid and subfoveal hotspots along with the fact that these lesions were diagnosed early in the disease suggests that this study included unusually aggressive lesions (Slakter et al 2005). C-02-47: pharmacokinetics of RETAANE suspension in patients with AMD This was a pharmacokinetics (PK) study in 20 patients with wet AMD who had two PJD administrations of RETAANE suspension over a 12 month period. The peak plasma levels were correlated with observed reflux. It was found that the patients for whom reflux was observed had plasma levels 244 that were 4-fold lower than patients without reflux. These results highlighted the need for a CPD. C-04-50: pharmacokinetics and reflux study with counter pressure device Recognizing the need for a method to reduce reflux, the manufacturer of anecortave acetate (Alcon Laboratories, Inc.) initiated this study to determine the ability of a CPD to eliminate reflux. The study was done at the request of the FDA. This pharmacokinetic study was undertaken to determine whether reflux could be prevented and used serum drug levels as a quantitative, surrogate measure for the influence of reflux on drug absorption. Investigators evaluated and scored drug reflux following administration of RETAANE. Reflux was effectively controlled in 100% of patients, with a reflux score of 0 for all eyes (as rated by the investigator), consistent with no loss of dose upon administration using the CPD. Mean plasma drug levels were increased 4-fold over drug levels observed with reflux in the C-02-47 trial. Controlling reflux with the CPD is expected to provide improved visual acuity outcomes based on improved outcomes in patients without reflux in protocol C-01-99 relative to those with reflux (Figure 4). C-02-60: the anecortave acetate risk reduction trial. Several studies have shown that patients with wet AMD in one eye are at high risk of developing CNV in the fellow eye with dry AMD. It was found that patients with both large drusen (larger than 63 µm) and retinal pigment epithelium hyperpigmentation in the fellow eye faced a 58% risk of developing CNV within 5 years. By comparison, patients without large drusen or hyperpigmentation in their fellow eye faced a much lower (10%) risk of developing CNV (Abdelsalam et al 1999). Another study found that if the fellow eye had 5 or more large drusen, it was more than twice as likely to develop CNV compared with a fellow eye with fewer or no drusen. The chances of CNV development were also found to be higher in eyes with confluent drusen and focal areas of hyperpigmentation. Amongst the 670 patients observed in this study, 236 (35%) developed CNV in the better eye within 5 years (BenEzra et al 1997). These epidemiological studies have provided the baseline data necessary for undertaking clinical trials studying prevention of wet AMD. The studies using this clinical model are extremely costly due to the large numbers Clinical Interventions in Aging 2006:1(3)