112 |
N. Steinle and P.K. Kaiser |
|
|
Triple Therapy for Exudative Age-Related Macular Degeneration
In order to further address the multifactorial pathogenesis of exudative AMD, investigators have begun to examine the combination of corticosteroids, VPDT, and anti-VEGF agents (Table 7.3) [139–143]. This regimen has been referred to by the descriptive term “Triple Therapy” [139]. One of the goals of triple therapy is to improve vision to a level comparable to antiVEGF monthly monotherapy while reducing the number of treatments in patients with CNV due to AMD. One of the first published reports on triple therapy was a prospective, noncomparative, interventional case series of 104 patients [139]. In contrast to the previous studies with reducedfluence, VPDT was administered in a reduced– duration fashion (42 J/cm2, accomplished by light delivery time of 70 s). Approximately 16 h after VPDT, dexamethasone (800 mg) and bevacizumab (1.5 mg) were injected intravitreally. Dexamethasone was selected over IVTA since dexamethasone could be injected as a solution and thus was more rapidly cleared from the vitreous than IVTA suspensions (thereby possibly reducing unwanted corticosteroid side effects) [139]. Patients attended follow-up visits every
six weeks, and fluorescein angiography was performed every three months or earlier if OCT showed significant edema. All 104 patients received one triple therapy cycle (five patients received a second triple treatment due to remaining CNV activity). The triple therapy was complemented in 18 patients (17.3%) by an additional intravitreal injection of bevacizumab. The mean follow-up period was 40 weeks (range, 22–60 weeks). Mean increase in visual acuity was 1.8 lines, which was significant. Mean decrease in retinal thickness was also significant (182 mm). No serious adverse events were observed. Thus, the study concluded that in most patients with CNV due to AMD, triple therapy resulted in significant and sustained visual acuity improvement after only one cycle of treatment. In addition, the therapy was found to be safe and convenient for patients, all at a potentially lower cost compared with therapies that must be administered more frequently [139].
Another study investigating triple therapy examined consecutive patients with subfoveal CNV secondary to AMD [140]. Patients were treated with standard-fluence VPDT using a standard protocol (600 mW/cm2 for 83 s to deliver 50 J/cm2) immediately followed by 1.25 mg of bevacizumab and 4 mg of IVTA. Then, 1.25 mg
Table 7.3 Completed studies investigating the use of triple therapy in patients with CNV due to exudative AMD
Investigator
Augustin et al. [139]
Yip et al. [140]
Ehmann et al. [141]
Bakri et al. [142]
Ahmadieh et al. [143]
Number |
|
|
|
|
|
of eyes |
Initial Regimen |
PDT |
Steroid |
Anti-VEGF |
Follow Up |
104 |
VPDT then |
Reduced-duration |
800 mg IVD |
1.5 IVB |
40 weeks |
|
vitrectomy 16 h later |
(600 mW/cm2 for 70 s |
(0.2 mL) |
(0.06 mL) |
|
|
with IVD + IVB |
to deliver 42 J/cm2) |
|
|
|
36VPDT + immediate IVTA + IVB
32VPDT + IVD then IVB 1 and 7 week later
31Consecutive VPDT + IVD + IVB
Standard-fluence |
4 mg IVTA |
1.25 IVB |
6 months |
|
(600 mW/cm2 |
for 83 s |
(0.1 mL) |
(0.05 mL) |
|
to deliver 50 J/cm2) |
|
|
|
|
Reduced-fluence |
800 mg IVD |
1.25 IVB |
12 months |
|
(300 mW/cm2 |
for 83 s |
(0.08 mL) |
(0.05 mL) |
|
to deliver 25 J/cm2) |
|
|
|
|
Reduced-fluence |
200 mg IVD |
1.25 IVB |
12 months |
|
(300 mW/cm2 |
for 83 s |
(0.05 mL) |
(0.05 mL) |
|
to deliver 25 J/cm2)
17 |
VPDT then 48 h |
Standard-fluence |
2 mg IVTA |
1.25 IVB |
50 weeks |
|
later IVB + IVTA |
(600 mW/cm2 for 83 s |
(0.05 mL) |
(0.05 mL) |
|
|
|
to deliver 50 J/cm2) |
|
|
|
IVB intravitreal bevacizumab, IVD intravitreal dexamethasone, IVTA intravitreal triamcinolone acetonidel, VPDT verteporfin photodynamic therapy