172
5. Combined treatments
Combined approaches for treating exudative AMD have
been investigated as a mean of improving treatment
efficacy and reducing treatment frequency. Many non-
randomized studies reported successful treatment using
combinations of PDT, corticosteroids and antiangiogenic
agents
(22,23,24)
. The Focus trial
(19)
showed that combina-
tion therapy using PDT and Ranibizumab was superior
to PDT alone in efficacy and also reduced the need for
repeat PDT sessions. A merely illustrative comparison of
Although the complete results report has not been pub-
lished, the primary endpoint had not been reached at 12
and 24 months; therefore, no significant benefits were
demonstrated for the treatment of occult membranes with
PDT. These results led the EMEA to remove occult mem-
branes from the list of photodynamic therapy indications
(April 2007).
3.5 Meta-analysis of the TAP and VIP studies
The meta-analysis of the TAP and VIP studies was a ret-
rospective analysis in which lesion size, composition and
visual acuity at baseline were considered, as well as possible
relations between these parameters and study results. The
objective of this meta-analysis was to explain the appar-
ent discrepancies found between the TAP and VIP study
results, considering the following:
- in the TAP study, treatment was found to be benefi-
cial in predominantly classic and occult lesions, whereas it
was found not to be beneficial in minimally classic lesions;
- in the VIP study, treatment of occult lesions was found
to be more beneficial in small lesions (≤4 disc areas) and/
or visual acuity <20/50. This meta-analysis revealed that
the most important factor in predicting final visual acu-
ity in patients treated with PDT appears to be lesion size.
Therefore, treatment of small lesions (≤4 disc areas) will be
beneficial for all types of lesions, including occult lesions
with no classic component, provided lesions are recent.
Regarding classic membranes, treatment benefits extend
to lesions > 4 DA and non-recent lesions.
3.6 TAP Extension
Some patients that completed the 2-year TAP were
enrolled in a 3-year extension study, for a total duration
of 5 years (60 months), under an open-label regime. The
main objective of this study was to obtain long-term visual
acuity and 5-year safety data in patients with subfoveal
choroidal neovascularization treated with photodynamic
therapy. Patients having completed month 24 of the
TAP study were eligible to participate in the study exten-
sion, irrespectively of having been included in the treat-
ment or the placebo group and of lesion characteristics
at baseline. In the TAP study extension, visual outcomes
remained stable between month 24 and month 60, even
in patients with low retreatment rates. No safety problems
were found leading to contraindications being associated
to retreatment with photodynamic therapy in the 5 years
of study duration. No safety problems were found in bilat-
eral treatment.
4. PDT Safety
The most complete and extensive PDT safety data were
published in the meta-analysis of the TAP and VIP stud-
ies, where a comparison with placebo was performed.
PDT is considered a safe treatment, with rare side effects,
of little significance (Table 3). Choroidal hypoperfusion
associated to PDT has been documented in fluorescein
and ICG angiography in the first days after treatment
and, more rarely, in the following months. Controversy
exists regarding the cumulative effect of treatment in
permanent occlusion of the normal choriocapillaris and
the association between this hypoperfusion and eventual
functional consequences
(21)
.
Ocular effects
Non-specific visual disorders
Transient loss of visual acuity (18% vs. 0%)
Severe loss of visual acuity (≥ 20 letters
up to 7 days after PDT) (0.7% vs. 0%)
Scotomatous alterations (6% vs. 3.4%)
Systemic effects
Injection site reactions (13% vs. 5.6%)
Lower back pain (2.4% vs. 0%)
Hypersensitivity reactions (3% vs. 0%)
Sleep pattern alterations (1.6% vs. 0%)
Table 3 – PDT adverse effects
