198
Based on efficacy in terms of visual acuity and considering
the level of clinical evidence for the studies performed, it
is possible to conclude that no level I evidence exists to
recommend combined treatment instead of monotherapy.
However, if both clinical efficacy and efficiency (smaller
number of treatment sessions required; longer absence of
active disease between treatments; smaller drug, staff and
structural costs; smaller doses/increased tolerance) criteria
are considered, combined treatment based on anti-VEGF
agents should be favoured in most forms of exudative
AMD, as early as possible, as suggested also by several
studies with levels of evidence II-1 and II-2 and numerous
studies with levels of evidence II-3 and III. Clinical criteria
and the doctor’s experience should also weight significantly
in deciding whether or not to opt for combined treatment.
7.1 Particular cases of AMD
Due to their poor response to monotherapy, cases of
Correspondence concerning this article can be sent directly to the authors through the emails:
Retinal Angiomatous Proliferation (RAP) and Polypoid
Choroidal Vasculopathy should be primary candidates
for anti-VEGF-based combined treatment.
7.2 Improved healthcare and increased equity
If combined treatments are proved to lead to better out-
comes (greater VA line gains) or more sustained gains, as
referred in most studies, the superior clinical efficacy of
this treatment approach will be established.
Although the costs of two or three different treatments
need to be considered when calculating combined treat-
ment costs. Costs per patient will be reduced if fewer
overall resources are used. This is a more efficient strat-
egy, as well as a principle to follow in health economics:
to manage scarce resources so that health investments
may benefit more patients, instead of necessarily making
expense cuts. It is also about increasing equity – increas-
ing the number of patients benefiting from treatment
(1)
.
Levels of clinical evidence
Level I – At least one well-designed study – randomized, controlled
studies.
Level II-1 – High-quality, non-randomized, controlled studies.
Level II-2 – Studies with a control group involving more than one
research centre or group.
Level II-3 – Studies with no control group; series studies, with or
without intervention.
Level III – Opinion of respected authorities, based on clinical experi-
ence, descriptive studies or specialised committee reports.
Abbreviations
ACE - angiotensin converting enzyme
AR - angiotensin receptor
ICAM-1- Intercellular Adhesion Molecule-1
SDF-1-CRXR4 Axis – Stromal-Derived Factor-1 and its CRXR-4
receptor
PEDF- Pigment Epithelium-Derived Factor
VEGF- Vascular Endothelial Growth Factor
