StemCONN2015 4/27/15 program-2 - Final Program Download
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1. Correspondence
www.thelancet.com Vol 386 July 4, 2015 29
*Brent A Neuschwander-Tetri,
Mark LVan Natta, JamesTonascia,
Elizabeth M Brunt, David E Kleiner
tetriba@slu.edu
Saint Louis University, St Louis, MO, USA (BAN-T);
Johns Hopkins University, Baltimore, MD, USA
(MLVN, JT);Washington University, St Louis, MO,
USA (EMB); and National Cancer Institute,
Bethesda, MD, USA (DEK)
1 Neuschwander-Tetri BA, Loomba R, Sanyal AJ,
et al. Farnesoid X nuclear receptor ligand
obeticholic acid for non-cirrhotic,
non-alcoholic steatohepatitis (FLINT):
a multicentre, randomised, placebo-controlled
trial. Lancet 2015; 385: 956–65.
Stem cells in age-related
macular degeneration
and Stargardt’s macular
dystrophy
I read with great interest the
Article by Steven Schwartz and
colleagues (Feb 7, p 509),1
which
reported the results of treatment
of 18 patients with advanced dry
age-related macular degeneration
and Stargardt’s disease (juvenile
macular degeneration). However, an
important factor to interpret these
results is that these types of macular
degeneration are different from
wet macular degeneration, in which
visual improvement increases as fluid
leakage and bleeding decrease.
Advanced dry macular degeneration
and Stargardt’s disease cause blind
areas (scotomas) in the macula in
which the photoreceptor cells and
the retinal pigment epithelial cells
have degenerated and are no longer
present. Transplantation of stem-cell
derived retinal pigment epithelial
cells cannot restore vision but might
be able to prevent further disease
progression.
When a scotoma affects the foveal
centre, the patient needs to learn
how to move fixation out of the blind
area onto seeing retina. This skill has
often not been developed for the
worse-seeing eye of patients with
bilateral macular degeneration; the
patient adaptsto usethe better-seeing
eye effectively, and the worse-seeing
eye might often leave the image
unseen in the scotoma. Low vision
rehabilitation can help these patients
to use their remaining seeing retina
more effectively.
Most eye-care specialists have had
a patient explaining to them that
the worse eye is useless and then
1 or 2 years later report that the worse
eye has improved. In a large natural
history study2,3
of bilateral advanced
dry age-related macular degeneration,
we identified that nearly 20% of
patients spontaneously improved
by two or more lines of vision in
their worse-seeing eye over time,
despite the fact that the area of the
scotoma had enlarged further. With a
fundus microperimeter, which allows
visualisation of the retina and where
a person fixates a target, we identified
that the eyes that improved were
unable to move the fixation target
out of the scotoma onto seeing retina
at baseline, whereas at 3 years later,
these patients could put the fixation
target on eccentric seeing retina
and see it. This outcome accounts
for the improvement in vision that
the patients had despite worsening
of the disease. Other investigators4
have shown that progress in fixation
stability resulted in improvements in
reading acuity, speed, and the critical
print size for maximum reading.
This improvement of vision in the
worse eye surely comes into play
when interest is focused on repeated
testing or administration of treatment
to that eye. To try to circumvent this
issue, short-term low vision training
would be worthwhile before a clinical
trial to get the patient accustomed
to using their eye effectively;
thereafter, a change can be
attributed to the treatment. Alterna-
tively, microperimetry should be done
to verify that the patient is able to
fixate on seeing eccentric retina before
the patient is treated. The results of
the trial by Schwartz and colleagues
are encouraging, but careful analysis
of the reported improvement in visual
acuity is needed. I am hopeful that
after adequate testing, true visual
acuity improvement from successful
therapy can be shown.
JS has been a consultant to several companies
designing clinical trials for advanced dry macular
degeneration and Stargardt disease, including
Advanced CellTechnology, Acucela, Alcon
(Novartis), Alexion, BioMarin, Cell Cure, Genentech
(Roche), Intrexon, Janssen, Pfizer, Stemcells, and
Sucampo during the past 3 years.
Janet S Sunness
jsunness@gbmc.org
Richard E Hoover LowVision Rehabilitation
Services, Greater Baltimore Medical Center, and the
Department of Ophthalmology andVisual Sciences,
University of Maryland School of Medicine,
Baltimore, MD 21204, USA
1 Schwartz SD, Regillo CD, Lam BL, et al. Human
embryonic stem cell-derived retinal pigment
epithelium in patients with age-related
macular degeneration and Stargardt’s macular
dystrophy: follow-up of two open-label phase
1/2 studies. Lancet 2015; 385: 509–16.
2 Sunness JS, Applegate CA, Gonzalez-Baron J.
Improvement of visual acuity over time in
patients with bilateral geographic atrophy
from age-related macular degeneration. Retina
2000; 20: 162–69.
3 Sunness JS. Spontaneous improvement in
visual acuity in age-related geographic atrophy
of the macula. JAMA Ophthamol 2014;
132: 356–57.
4 Tarita-Nistor L, González EG, Markowitz SN,
Steinbach MJ. Plasticity of fixation in patients
with central vision loss. Vis Neurosci 2009;
26: 487–94.
The results of Steven Schwartz
and colleagues’ study1
on human
embryonic stem cell (hESC)-derived
retinal pigment epithelium in
patients with age-related macular
degeneration and Stargardt’s macular
dystrophy are very exciting; however,
we have some concerns about the
interpretation of the study.
First, a prospective clinical trial with
so few patients is extremely difficult to
interpret definitively for either toxic
effects or efficacy.
Second, the optimum density of
hESCs that provides the maximum
benefit to reduce the various
unmet medical disorders with
minimum toxic effects remains to
be determined. Are there any data
about the dose-associated benefits
of human embryonic stem cells? If
yes, what are the exact differences
between densities?
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