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BRV893-2/11 RO0311_Ista Bepreve.indd 1 2/24/11 11:56 AM RO0311_Ista PI.indd 1 2/24/11 12:01 PM WNEWS E I V E R 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 W News E I V E R 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 Sightpath OnDemand™ Surgical Equipment and Services Perform cataract, refractive, and glaucoma surgeries where you want, when you want. Sightpath OnDemand™ equipment and services is a complete solution that enables you to meet your patients’ surgical needs at your own location. You can stop outsourcing surgeries to referral sites and start providing the best kind of care possible—the kind that’s closest to your patients’ home. 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Box 25542, London, ON N6C 6B2.V 8 | Review of Ophthalmology | March 2012 004_rp0312_news.indd 8 2/24/12 1:39 PM SOME SURFACES ARE WORTH PROTECTING THE OCULAR SURFACE IS ONE. Surface Protection and More © 2011 Novartis 11/11 SYS11179JAD 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). RP0312_Alcon Systane.indd 1 2/2/12 12:59 PM Visit us at Right On Target... 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