The “triple” association of PDT with anti-angio- genic and anti-inflammatory therapies has been under debate for a long time [7]. RADICAL (Reduced Fluence Visudyne Anti-VEGF-Dexamethasone In Combination for AMD Lesions) evaluated this approach in a phase II study. The overall results showed that fewer retreatment visits were required with the combination therapies than with ranibizumab monotherapy, and that the differences were statistically significant:

Triple therapy with quarter-fluence PDT followed by ranibizumab and then dexamethasone (P = 0.04).

Triple therapy with half-fluence PDT followed by ranibizumab and then dexamethasone (P < 0.001).

Double therapy with half-fluence PDT followed by ranibizumab s (P = 0.04).

While the mean visual acuity may appear to have improved similarly across all treatment groups, the confidence intervals were wide. There were no unexpected safety findings, and adverse event incidence was similar across treatment groups.

At 12 months, while all combination groups had significantly fewer retreatment visits than the ranibizumab monotherapy group, the better results (both in VA change and retreatment visits) in the triple therapy half-fluence group compared with the other combination groups were a trend and not statistically different. The AE rates were similar among groups and no new safety signals were observed in 12 months. The combination groups received fewer retreatments over the 12-month study period.

13.7.1 Laser Photocoagulation

Classic CNV that is well demarcated on fluorescein angiography and extrafoveal can be treated by direct focal photocoagulation. For cases in which photocoagulation might be considered, the benefits of laser treatment are limited. Fluorescein angiography should be repeated after a short interval for early detection of persistence or recurrence of the vascular membrane, which might need re-treatment with photocoagulation or another, more recently developed approach. Since the published trials, nearly 30 years ago, a large amount of knowledge has been acquired, and numerous new technologies are available that would probably modify the results of the laser photocoagulation studies. Nowadays, it seems inconceivable to apply laser photocoagulation to so called “extrafoveal classic” CNV without ruling out associated subfoveal occult CNV, or polypoidal choroidal vasculopathy, or chorioretinal anastomosis on ICG angiography, or an early fluid accumulation on OCT. The extremely rare extrafoveal subepithelial occult CNV might benefit from that easy treatment approach if the fovea is threatened. Subfoveal laser treatment has always been poorly accepted, because laser photocoagulation damages the fovea overlying the treated CNV, subsequently resulting in immediate visual loss. This undesirable effect and the advent of newer treatment options has made thermal laser photocoagulation a seldom-used treatment for subfoveal classic CNV.

13.7Present Guidelines

Until recently, laser photothermal and photodynamic therapy have been the only treatments that have demonstrated benefit in large controlled clinical trials for the management of AMD-related CNV. Each of the treatments reported so far concentrates mainly on one aspect of AMD-associated CNV (e.g., laser photocoagulation on the newly grown vessels) and therefore has strengths and weaknesses.

It is extremely difficult to establish universal standards and criteria on which the treatment decision can be based. As guidance, if the natural history of the disease would be worse than after treatment, the treatment can be considered. The condition of the other eye may help in this decision [10].

13.7.2 Photodynamic Therapy

Specific indications of PDT remain. Classic CNV located primarily underneath the fovea can be treated with photodynamic therapy. A significant number of non-responders to anti-VEGF monotherapy may have underlying polypoidal choroidal vasculopathy responding well to PDT. Despite the positive benefits, there are several factors that may limit the use of antiVEGF monotherapy. Some patients are considered unsuitable to receive this treatment, including those with a chronic ocular or periocular infection. In addition, anti-VEGF monotherapy does not improve vision in all patients, such as those with chorioretinal anastomosis or fibrovascular pigment epithelial