Current Opinion in Investigational Drugs

18
Editorial overview
Steroid therapy for exudative age-related macular degeneration: Bridging
the gap until a cure is found
Maneli Mozaffarieh & Andreas Wedrich*
Address
Department of Ophthalmology
Medical University of Graz
Auenbruggerplatz 4
A-8036 Graz
Austria
Email: andreas.wedrich@meduni-graz.at
* To whom correspondence should be addressed
Current Opinion in Investigational Drugs 2006 7(1):18-19
© The Thomson Corporation ISSN 1472-4472
Age-related macular degeneration (AMD) is a devastating
disease affecting individuals of over 50 years of age, and is
the leading cause of irreversible blindness in the developed
world [1,2]. It is estimated that 1.6% of the population in the
50- to 65-year-old age group is affected, and in the UK there
are 16,000 new cases per year. The implications of this
untreatable disease in terms of social impact, healthcare
costs and personal misery are considerable. Current
treatments for both the wet and dry forms of the disease are
of limited efficacy [3], and, therefore, there is keen interest
among scientists and physicians to develop new therapies.
Corticosteroids have long been the cornerstone of ocular
anti-inflammatory therapy. In addition, they can suppress
cell proliferation. Consequently, steroids have been used for
the treatment of several ocular diseases, administered either
locally or systemically. In recent years, one particular
steroid, triamcinolone acetonide, has received much
attention from scientists. Various researchers studied the
possibility of injecting this corticosteroid directly into the
eye, firstly in animals [4,5] and later in selected patients. The
intravitreal use of this corticosteroid gained popularity
amongst ophthalmologists for the treatment of a wide range
of retinal diseases, including diabetic and cystoid macular
edema and exudative AMD.
Steroids, along with the majority of other drugs, do not exert
solely beneficial effects. One common side effect is the rise of
intraocular pressure (IOP) that is associated with steroid use.
This issue was addressed in a study where a group of
known steroid responders were treated with four different
steroids topically [6]. The results of this study showed that
IOP did not begin to increase until after 3 and 5 weeks of
treatment. The beauty of this finding for ophthalmologists
was that in the worst-case scenario, there remains a 3-week
window of relative safety when treating with a topical
ophthalmic corticosteroid. Moreover, almost all patients
with primary-care conditions respond to treatment in less
than 2 weeks when the steroid is applied topically.
Therefore, should we be concerned about the risk of IOP
elevation after triamcinolone acetonide intravitreal use for
exudative AMD? Furthermore, do we increase the chances
of improved vision for patients in the long term when
injecting this steroid through the intravitreal route? The
results of some of the research that has been conducted in
this area show that even 4 mg of intravitreal triamcinolone
significantly raises IOP [7,8]. In one particular study, the
researchers describe using 25 mg of triamcinolone for
intravitreal injections [9], which may increase IOP even more
significantly. The investigators suggested that the advantage of
a higher dose would be the longer intraocular availability of the
drug [10], rather than the temporary visual improvements
encountered in patients after intravitreal injections [8], despite
the possible side effects. It appears that our scientific
enthusiasm for possible visual improvements in exudative
AMD with steroid injections has forced us to step sideways.
Indeed, various studies suggest that in exudative AMD, the
modes of action of triamcinolone are linked to the
downregulation of inflammatory markers and endothelial
cell permeability [11,12]. However, moderate-to-high
concentrations of this drug would be required at the site of
action in order to prevent further growth of subretinal
neovascular tissue. For patients, this requirement would mean
that triamcinolone must be injected repeatedly, otherwise visual
improvements would only occur in the short term [8]. The
question that then arises is up to how many intravitreal
injections of this steroid can be tolerated by the eye of each
patient? Unfortunately, most of the research that has been
conducted in this area to date has not been associated with a
long enough follow-up time, one of the longer follow-up times
being 18 months [7]. We therefore do not have a fair idea of the
actual long-term outcome (ie, visual improvement or the side
effects of this drug), particularly when injecting via the
intravitreal route more than once.
Another concern when using intravitreal steroids is the
association of steroid use with an increase in lens opacity. In
one particular study in which intravitreal injections of
triamcinolone were administered for the treatment of diffuse
diabetic macular edema [13], a 3-fold increase of the posterior
subcapsular cataract score among phakic patients occurred.
This trend toward cataract progression suggests that cataract is
a likely risk of steroid injections. Cataracts influence quality-oflife
measures [14], and therefore a delay of cataract onset could
have a tremendous influence on the health of patients and on
healthcare costs. The issue of cataract progression is also of
particular interest for patients with AMD, because there is
controversy regarding the possible benefits or risks of cataract
surgery in these patients. While some reports suggest that
cataract surgery may worsen the progression of AMD [15,16],
others describe a benefit [17,18]. It may therefore be more
justified to resist the temptation to treat patients with multiple
intravitreal steroid injections as there is currently no evidence
of long-term benefits and, by increasing the chances of
cataracts, patients may become more vulnerable to possible
side effects after surgery.
A further side effect of corticosteroid injections is steroidinduced
infection [19,20]. Some researchers have reported