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96 Pages·2012·19.08 MB·English

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Volume XIX • No. 3 • March 2012
Further Gene Therapy Improves
Vision in Patients with LCA
Gene therapy for congenital blindness in light sensitivity, side vision and gene called RPE65 that is mutated
has taken another step forward, say other visual functions.” in one form of LCA.
researchers from the Children’s Other objective results came The researchers in the current
Hospital of Philadelphia and the from brain signals seen in neuro- study previously carried out a clini-
Perelman School of Medicine imaging. When a dimly fl ickering cal trial of this gene therapy in 12
at the University of Pennsylva- checkerboard pattern fl ashed in patients with LCA, four of them
nia. Three adult patients previously front of a patient’s recently treated children aged 11 and younger
treated in one eye received the same eye, an area in the brain respon- when they were treated. Exercising
treatment in their other eye, and the sible for vision lit up during func- caution, the researchers treated
patients became better able to see in tional magnetic resonance imaging. only one eye—the one with worse
dim light; two were able to navigate “This fi nding is telling us that the vision. This trial, reported in Oc-
obstacles in low-light situations. No brain is responding to the eye’s sen- tober of 2009, achieved sustained
adverse effects occurred. sitivity to dim light,” said radiology and notable results, with six sub-
Neither the fi rst treatment nor researcher Manzar Ashtari, PhD, jects improving enough to no lon-
the readministered treatment trig- of Children’s Hospital of Philadel- ger be classifi ed as legally blind.
gered an immune reaction that phia, the study’s co-leader. The research team’s experiments
cancelled the benefi ts of the in- LCA is a group of hereditary reti- in animals had showed that read-
serted genes, as has occurred in hu- nal diseases in which a gene muta- ministering treatment in a second
man trials of gene therapy for other tion impairs production of an en- eye was safe and effective. While
diseases. The current research tar- zyme essential to light receptors in these results were encouraging,
geted Leber congenital amaurosis, the retina. The study team injected the researchers were concerned
a retinal disease that progresses patients with a vector, a genetically that readministering the vector in
to total blindness by adulthood. engineered adeno-associated virus, the untreated eye of the patients
The work was reported in Science which carried a normal version of a might stimulate an infl ammatory
Translational Medicine. response that could re-
“Patients have told duce the initial benefi ts
us how their lives have in the untreated eye.
changed since receiving “Our concern was that
gene therapy,” said study the fi rst treatment might
co-leader Jean Bennett, cause a vaccine-like im-
MD, PhD, the F.M. Kir- mune response that
by professor of ophthal- could prime the indi-
mology at Penn. “They vidual’s immune system
are able to walk around to react against a repeat
at night, go shopping for exposure,” said Dr. Ben-
groceries and recognize nett. Because the eye
people’s faces—all things is immune-privileged,
they couldn’t do before. such a response was
At the same time, we considered less likely
were able to objectively than in other parts of the
measure improvements The Children’s Hospital of Philadelphia body, but the idea needed
4 | Review of Ophthalmology | March 2012
004_rp0312_news.indd 4 2/24/12 2:22 PM
to be tested in practice.
As in the fi rst study, retina spe-
cialist Albert M. Maguire, MD, a
Rhein Fire & Ice Mask
study co-author, injected the vector
into the untreated eyes of the three Product #85-9005
subjects at the Children’s Hospital
of Philadelphia. The patients had
been treated one and a half to three
years previously.
The researchers continued to fol-
low the three patients for six months
after readministration. They found
the most signifi cant improvements
were in light sensitivity, such as the
pupil’s response to light over a range
of intensities. Two of the three sub-
jects were able to navigate an obsta-
cle course in dim light, as captured
in videos that accompanied the pub-
lished study.
There were no safety problems
and no significant immune re-
sponses. There was even an unex-
pected benefit—the fMRI results
showed improved brain responses
not just in the newly injected eye,
but in the first one as well, possibly
because the eyes were better able
to coordinate with each other in
fixating on objects.
The researchers caution that
(cid:115)(cid:0) (cid:38)(cid:79)(cid:82)(cid:0)(cid:40)(cid:69)(cid:65)(cid:84)(cid:0)(cid:52)(cid:72)(cid:69)(cid:82)(cid:65)(cid:80)(cid:89)(cid:26)(cid:0)(cid:48)(cid:76)(cid:65)(cid:67)(cid:69)(cid:0)(cid:41)(cid:84)(cid:0)(cid:41)(cid:78)(cid:0)(cid:33)(cid:0)(cid:45)(cid:73)(cid:67)(cid:82)(cid:79)(cid:87)(cid:65)(cid:86)(cid:69)(cid:0)(cid:0)(cid:0)
follow-up studies must be done
(cid:0) (cid:38)(cid:79)(cid:82)(cid:0)(cid:17)(cid:21)(cid:0)(cid:51)(cid:69)(cid:67)(cid:79)(cid:78)(cid:68)(cid:83)(cid:12)(cid:0)(cid:55)(cid:65)(cid:82)(cid:77)(cid:0)(cid:50)(cid:69)(cid:76)(cid:73)(cid:69)(cid:70)(cid:0)(cid:44)(cid:65)(cid:83)(cid:84)(cid:83)(cid:0)(cid:17)(cid:21)(cid:0)(cid:45)(cid:73)(cid:78)(cid:85)(cid:84)(cid:69)(cid:83)(cid:14)
over a longer period and with ad-
ditional subjects before they can (cid:115)(cid:0) (cid:38)(cid:79)(cid:82)(cid:0)(cid:35)(cid:79)(cid:76)(cid:68)(cid:0)(cid:52)(cid:72)(cid:69)(cid:82)(cid:65)(cid:80)(cid:89)(cid:26)(cid:0)(cid:33)(cid:70)(cid:84)(cid:69)(cid:82)(cid:0)(cid:48)(cid:76)(cid:65)(cid:67)(cid:73)(cid:78)(cid:71)(cid:0)(cid:41)(cid:78)(cid:0)(cid:52)(cid:72)(cid:69)(cid:0)(cid:38)(cid:82)(cid:69)(cid:69)(cid:90)(cid:69)(cid:82)(cid:0)
defi nitively state that readminister- (cid:0) (cid:18)(cid:0)(cid:40)(cid:79)(cid:85)(cid:82)(cid:83)(cid:12)(cid:0)(cid:35)(cid:79)(cid:79)(cid:76)(cid:0)(cid:50)(cid:69)(cid:76)(cid:73)(cid:69)(cid:70)(cid:0)(cid:44)(cid:65)(cid:83)(cid:84)(cid:83)(cid:0)(cid:17)(cid:21)(cid:0)(cid:45)(cid:73)(cid:78)(cid:85)(cid:84)(cid:69)(cid:83)(cid:14)
ing gene therapy for retinal disease
(cid:115)(cid:0) (cid:41)(cid:78)(cid:67)(cid:76)(cid:85)(cid:68)(cid:69)(cid:83)(cid:0)(cid:35)(cid:76)(cid:79)(cid:84)(cid:72)(cid:0)(cid:51)(cid:76)(cid:69)(cid:69)(cid:86)(cid:69)(cid:0)(cid:38)(cid:79)(cid:82)(cid:0)(cid:33)(cid:68)(cid:68)(cid:73)(cid:84)(cid:73)(cid:79)(cid:78)(cid:65)(cid:76)(cid:0)(cid:44)(cid:73)(cid:68)(cid:0)
is safe in humans. However, said
(cid:0) (cid:48)(cid:82)(cid:79)(cid:84)(cid:69)(cid:67)(cid:84)(cid:73)(cid:79)(cid:78)(cid:14)
Dr. Bennett, the fi ndings bode well
for treating the second eye in the
(cid:115)(cid:0) (cid:37)(cid:65)(cid:83)(cid:89)(cid:0)(cid:52)(cid:79)(cid:0)(cid:53)(cid:83)(cid:69)(cid:12)(cid:0)(cid:33)(cid:78)(cid:68)(cid:0)(cid:35)(cid:65)(cid:78)(cid:0)(cid:34)(cid:69)(cid:0)(cid:35)(cid:76)(cid:69)(cid:65)(cid:78)(cid:69)(cid:68)(cid:0)(cid:33)(cid:78)(cid:68)(cid:0)(cid:50)(cid:69)(cid:85)(cid:83)(cid:69)(cid:68)(cid:0)(cid:0)
remaining patients from the fi rst
(cid:0) (cid:45)(cid:85)(cid:76)(cid:84)(cid:73)(cid:80)(cid:76)(cid:69)(cid:0)(cid:52)(cid:73)(cid:77)(cid:69)(cid:83)(cid:14)
trial—including children, who may
have better results because their (cid:115)(cid:0) (cid:33)(cid:86)(cid:65)(cid:73)(cid:76)(cid:65)(cid:66)(cid:76)(cid:69)(cid:0)(cid:21)(cid:0)(cid:53)(cid:78)(cid:73)(cid:84)(cid:83)(cid:0)(cid:48)(cid:69)(cid:82)(cid:0)(cid:34)(cid:79)(cid:88)(cid:14)
retinas have not degenerated as
much as those of the adults.
(cid:38)(cid:79)(cid:82)(cid:0)(cid:45)(cid:79)(cid:82)(cid:69)(cid:0)(cid:41)(cid:78)(cid:70)(cid:79)(cid:82)(cid:77)(cid:65)(cid:84)(cid:73)(cid:79)(cid:78)(cid:0)(cid:35)(cid:65)(cid:76)(cid:76)(cid:0)(cid:23)(cid:18)(cid:23)(cid:13)(cid:18)(cid:16)(cid:25)(cid:13)(cid:18)(cid:18)(cid:20)(cid:20)
Further, Dr. Bennett added, the
research holds promise for using a
similar gene therapy approach for
other retinal diseases. Dr. Ashtari
said that fMRI may play a future
role in helping to predict patients
RHEIN CODE VIDEO CODE
more likely to benefi t from gene
3360 Scherer Drive, Suite B, St. Petersburg, FL 33716
therapy for retinal disease. (cid:24)(cid:16)(cid:16)(cid:13)(cid:22)(cid:19)(cid:23)(cid:13)(cid:20)(cid:19)(cid:20)(cid:22)(cid:0)(cid:115)(cid:0)(cid:52)(cid:69)(cid:76)(cid:26)(cid:0)(cid:23)(cid:18)(cid:23)(cid:13)(cid:18)(cid:16)(cid:25)(cid:13)(cid:18)(cid:18)(cid:20)(cid:20)(cid:0)(cid:115)(cid:0)(cid:38)(cid:65)(cid:88)(cid:26)(cid:0)(cid:23)(cid:18)(cid:23)(cid:13)(cid:19)(cid:20)(cid:17)(cid:13)(cid:24)(cid:17)(cid:18)(cid:19)(cid:0)(cid:0)
(cid:37)(cid:77)(cid:65)(cid:73)(cid:76)(cid:26)(cid:0)(cid:41)(cid:78)(cid:70)(cid:79)(cid:32)(cid:50)(cid:72)(cid:69)(cid:73)(cid:78)(cid:45)(cid:69)(cid:68)(cid:73)(cid:67)(cid:65)(cid:76)(cid:14)(cid:67)(cid:79)(cid:77)(cid:0)(cid:55)(cid:69)(cid:66)(cid:83)(cid:73)(cid:84)(cid:69)(cid:26)(cid:0)(cid:87)(cid:87)(cid:87)(cid:14)(cid:50)(cid:72)(cid:69)(cid:73)(cid:78)(cid:45)(cid:69)(cid:68)(cid:73)(cid:67)(cid:65)(cid:76)(cid:14)(cid:67)(cid:79)(cid:77)
(cid:55)(cid:79)(cid:77)(cid:65)(cid:78)(cid:0)(cid:55)(cid:69)(cid:65)(cid:82)(cid:73)(cid:78)(cid:71)(cid:0)(cid:36)(cid:82)(cid:89)(cid:0)(cid:37)(cid:89)(cid:69)(cid:0)(cid:40)(cid:69)(cid:65)(cid:84)(cid:0)(cid:45)(cid:65)(cid:83)(cid:75)
RHEIN CODE VIDEO CODE
1301 Rev.C ACBB
004_rp0312_news.indd 5 2/24/12 1:39 PM
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Don’t Dismiss
by 147 percent from 2001 to 2009.” The research, by a team from the
Dr. Stein notes that, “Until these Institute of Ophthalmology at Univer-
Fields, Photos newer imaging devices can be dem- sity College London, was published in
onstrated to identify the presence the journal Neurobiology of Ageing.
of open-angle glaucoma and cap- The researchers identified two
Increased reliance on newer technolo- ture disease progression as well as changes in the eyes of the mice
gies—beyond visual fi eld testing and more traditional methods do, pro- that they think accounted for this
straightforward fundus photogra- viders should use these devices as improvement:
phy—to evaluate patients with and an adjunct to—not a replacement • The number of macrophages
suspected of having open-angle glau- for—visual fi eld testing and fundus was reduced considerably in the eyes
coma may undermine patient care. photography.” Such fi ndings suggest of the mice given vitamin D. Macro-
A study published in January’s that greater efforts need to be made phages work to fi ght off infections, but
Ophthalmology focused on trends to educate eye-care providers about in combating threats to the aged body
in eye-care provider use of three the importance of visual fi eld testing they can sometimes bring about dam-
methods for evaluating patients with in glaucoma management. age and infl ammation. Giving mice
open-angle glaucoma or suspected Several factors likely contribute to vitamin D not only led to reduced
glaucoma: visual fi eld testing, fundus the recent shift to newer technolo- numbers of macrophages in the eye,
photography and other ocular imag- gies. The newer imaging procedures but also triggered the remaining mac-
ing technologies. Among these newer are painless, can be performed quick- rophages to change to a different con-
imaging technologies, the three most ly, require little patient cooperation, fi guration. Rather than damaging the
commonly relied upon approaches do not rely on subjective patient in- eye, the researchers think that in their
are confocal scanning laser ophthal- put and often can be obtained with- new confi guration macrophages ac-
moscopy, scanning laser polarimetry out dilation of the patient’s pupils. By tively worked to reduce infl ammation
and optical coherence tomography. comparison, visual fi eld testing takes and clear up debris.
The fi ndings were based on claims longer to perform, requires more pa- • There was also a reduction
data of 169,917 individuals with open- tient effort and is largely subjective. among treated mice in deposits of
angle glaucoma and 395,721 individ- Financial incentives may also drive amyloid beta, a toxic molecule that
uals suspected of having glaucoma use of these newer technologies. accumulates with age. Infl ammation
aged 40 years and older enrolled in Since the imaging devices are ex- and the accumulation of amyloid beta
a national managed-care network pensive to purchase, the more tests are known to contribute, in humans,
between 2001 and 2009. “Over the eye-care providers order, the quicker to an increased risk of age-related
past decade, we found a substantial they can recoup equipment costs and macular degeneration. The research-
increase in the use of newer ocular eventually generate revenue. ers think that, based on their fi ndings
imaging devices and a dramatic de- (For a more extensive discussion in mice, giving vitamin D supple-
crease in the use of visual fi eld test- of this topic, see Glaucoma Manage- ments to people who are at risk of
ing in the management of patients ment, p. 70.) AMD might be a simple way of help-
with and suspected of having open- ing to prevent the disease.
angle glaucoma by ophthalmologists Professor Glen Jeffery, who led
British Study: Can
and optometrists,” says lead author the work, said, “When we gave older
Joshua D. Stein, MD, MS, a glau- Vitamin D Combat mice the vitamin D we found that de-
coma specialist at the University of posits of amyloid beta were reduced
Michigan Kellogg Eye Center. “Our Aging Vision Loss? in their eyes and the mice showed
results indicate that the odds of a pa- an associated improvement of vision.
tient undergoing visual fi eld testing Researchers in Britain have found that People might have heard of amyloid
decreased by 36 percent from 2001 vitamin D reduces the effects of beta as being linked to Alzheimer’s
to 2005, by 12 percent from 2005 to aging in mouse eyes and improves disease, and new evidence suggests
2009, and by 44 percent from 2001 the vision of older mice signifi cantly. that vitamin D could have a role in
to 2009. By comparison, the odds of The researchers hope that this might reducing its buildup in the brain. So,
undergoing testing using the newer mean that vitamin D supplements when we saw this effect in the eyes
ocular imaging devices increased by could provide a simple and effective as well, we immediately wondered
100 percent from 2001 to 2005, by way to combat age-related eye where else these deposits might be
24 percent from 2005 to 2009, and diseases in humans. being reduced.”
6 | Review of Ophthalmology | March 2012
004_rp0312_news.indd 6 2/24/12 1:39 PM
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References
1. Christensen MT, Blackie CA, Korb DR, et al. An evaluation of the performance of a novel lubricant eye drop. Poster D692 presented at: The Association for Research in Vision and Ophthalmology Annual Meeting; May 2-6,
2010; Fort Lauderdale, FL. 2. Lane S, Paugh JR, Webb JR, Christensen MT. An evaluation of the in vivo retention time of a novel artifi cial tear as compared to a placebo control. Poster D923 presented at: The Association for
Research in Vision and Ophthalmology Annual Meeting; May 3-7, 2009; Fort Lauderdale, FL. 3. Davitt WF, Bloomenstein M, Christensen M, et al. Effi cacy in patients with dry eye after treatment with a new lubricant eye drop
formulation. J Ocul Pharmacol Ther. 2010;26(4):347-353. 4. Alejandro A. Effi cacy of a Novel Lubricant Eye Drops in Reducing Squamous Metaplasia in Dry Eye Subjects. Presented at the 29th Pan-American Congress of
Ophthalmology in Buenos Aires, Argentina, July 7-9, 2011. 5. Wojtowica JC., et al. Pilot, Prospective, Randomized, Double-masked, Placebo-controlled Clinical Trial of an Omega-3 Supplement for Dry Eye. Cornea 2011:30(3)
308-314. 6. Geerling G., et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dysfunction. IOVS 2011:52(4).
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