Augustin e t a t e c a s e D e v a t r o c e n A a m s a l P 7 6 )5 L /4 m g (3 n x a m 2 C 1 0 C-04-50 With CPD No Reflux C-02-47 No CPD C-02-47 No CPD No Reflux With Reflux Figure 4 Evidence supports use of counter pressure device (CPD) for managing reflux. Plasma concentrations of anecortave desacetate in patients with the CPD (C- 04-50) were the same as the plasma concentrations in patients without the CPD and had no reflux (C-02-47). Patients (C-02-47) with reflux had 4 fold lower levels of anecortave desacetate than patients without reflux. In the C-04-50 study, the CPD prevented reflux in 100% of the patients. also increases stability. Studies on bioavailablility have been performed to further address this issue. Those studies have shown that patients that did not have reflux had greater systemic bioavailability as assessed by higher plasma concentrations of anecortave acetate (please see Figure 5). Finally, the PJD procedure does not require immediate follow-up visits and no safety issues with the procedure have been identified (Figure 3). The PJD procedure has been used in clinical trials to deliver more than 2500 juxtascleral depots in nearly 900 patients with no safety concerns reported (Regillo et al 2005). Some patients have received as many as seven PJD administrations. To date, no globe perforations, damage to the optic nerve, damage to posterior ciliary arteries, or other significant concerns regarding the cannula have been raised by investigators during studies. The adverse events most often attributed to the PJD administration procedure in all treatment groups are shown in Table 4. No events associated with PJD were serious, almost all were mild and transient, with similar frequency across all groups, and did not interrupt treatment (D’Amico et al 2003; Augustin et al 2005). 242 Clinical trials C-98-03: dose-response monotherapy study: RETAANE 15 mg (anecortave acetate suspension) or anecortave acetate (3 mg, 30 mg) versus placebo in AMD patients One hundred twenty eight patients with exudative subfoveal AMD were enrolled in a double-masked, dose-response study, beginning in 1999, to evaluate the safety and efficacy of anecortave acetate. Patients were randomized to receive anecortave acetate (30 mg, 15 mg, or 3 mg) or placebo via PJD administration every six months for a total of 24 months. The primary efficacy variable was the mean change from baseline in best-corrected ETDRS logMAR visual acuity. The secondary efficacy outcomes were: (a) preservation of vision (loss of less than three lines), (b) clinically significant worsening of vision (loss of at least three lines), (c) severe vision loss (loss of at least six lines), and (d) changes in CNV. T h e e ff i c a c y o f a n e c o r t a v e a c e t a t e 1 5 m g f o r maintaining vision and suppressing lesion growth in patients with exudative AMD have been confirmed by long-term study results. Anecortave acetate 15 mg was Clinical Interventions in Aging 2006:1(3)