53
Development and
Progression of AMD
6
Age-related macular degeneration (AMD) remains the
leading cause of irreversible vision loss in the devel-
oped world among individuals older than 50 years
(1,2,3)
.
Patients with intermediate to large soft/confluent dru-
sen with or without hyper or hypopigmentation areas in
the macula and no neovascular membrane or geographic
atrophy are considered to have early age related macu-
lopathy (ARM). Geographic atrophy and wet age related
degeneration (AMD) are more advanced forms of AMD
that are more often associated with vision disability.
Although the treatment of AMD has evolved to include
laser photocoagulation, photodynamic therapy, surgi-
cal macular translocation and antiangiogenic agents,
treatment options for advanced AMD are limited.
Furthermore, the early form of ARM, albeit less devas-
tating than the wet form, has even fewer viable treatment
options.
AMD is characterized by ageing changes at photorecep-
tors, retinal pigment epithelium (RPE), Bruch’s mem-
brane and choroid
(4,5,6)
. Such ageing changes are consid-
ered to play a major role in development and progression
of AMD. AMD is a bilateral disease and approximately
10 to 20 % of patients with early ARM will develop the
wet form of AMD. Whereas patients with early ARM
in both eyes are at increased risk of developing either
geographic atrophy or wet AMD, once wet AMD devel-
ops in one eye there is a higher risk of subsequent devel-
opment of choroidal neovascularization (CNV) in the
second eye
(7,8)
. Several funduscopic findings have been
associated with increased risk of development of CNV in
fellow eyes of patients with unilateral neovascular AMD.
Various reports have emphasized the devastating effects
of CNV in the visual function of these patients
(7,9,10)
.
It is crucial to understand the natural history of the
development of CNV or the process underlying the con-
version from early ARM to late AMD. A better under-
standing of the involved pathophysiologic process or the
identification of biomarkers for the conversion would
enhance our ability to diagnose and treat the wet AMD,
to develop better therapies and eventually to prevent
vision loss associated with the disease
(11)
.
This review summarizes the various biomarkers of
AMD and analyzes whether or not they may, one day,
be exploited to determine risks of disease onset, mea-
sure progression of disease or even assess the effects of
treatment of AMD. Potential biomarkers are important
to identify since some might be utilized to reflect the
disease state of a particular patient and to individual-
ize therapy. Although studies have yielded promising
results for nutrient and inflammatory biomarkers, these
results have been inconsistent. At present, the best avail-
able marker of AMD risk is single nucleotide polymor-
phisms (SNPs). SNPs in complement factor H (CFH)
and PLEKHA1/ARMS2/HtrA1 capture a substantial
fraction of AMD risk and permit the identification of
individuals at high risk of developing AMD.
Patients with AMD in the first eye are known to have
high risk of bilateral involvement. In prospective stud-
ies in white populations, the annual rate of fellow eye
involvement was reported to be around 6% to 9%
(9,12,13)
.
The characterization of early ARM phenotypes is chal-
lenging. By combining different imaging modalities of
the macula and correlating this information, we are bet-
ter able to determine the presence of functional macular
alterations in the fellow eye of patients with this disease.
1. Introduction
Author:
Maria Luz Cachulo, MD
Coimbra University Hospital - Coimbra, Portugal
