August 06, 2012
5 min read

Gene therapy, retinal implants may help restore sight in blind patients

New treatments for retinal degenerative diseases are under investigation.

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Many ophthalmologists, but especially non-ophthalmology physicians and the general public, are unaware of the burden of blindness, according to a physician.

Gary Brown, MD, MBA, told colleagues at the Wills Eye Institute Retinal Degenerations Mini-Symposium in Philadelphia that ophthalmologists underestimate the value that patients place on the quality of life related to vision loss.

“With very severe vision loss, less than or equal to 20/800, patients were willing to give up 63% of their theoretical remaining time of their life,” he said, whereas ophthalmologists who were polled determined that percentage to be significantly less. Patients with visual loss were polled with utility analysis, a validated instrument used to measure the quality of life associated with a health state.

And, blindness is expensive.

“The poorer a patient’s vision is, the higher the associated costs are,” Brown said, estimating the cost to take care of a person with 20/800 or less vision in their better eye to be more than $80,000 annually.

“The burden upon quality of life is severe, but the burden upon financial well-being for people who are blind is just as severe,” Brown said.

In the pipeline, however, are promising advancements for treating retinal degeneration. Among them are gene therapy and retinal implants.

Gene therapy

Gene therapy to treat congenital blindness is not a new concept.

Jean Bennett, MD, PhD 

Jean Bennett

In 2008, Jean Bennett, MD, PhD, announced that a surgical procedure could restore and improve vision in patients with Leber congenital amaurosis (LCA). The procedure involves a subretinal injection of a vector carrying a normal version of the gene that causes LCA, called RPE65, into the affected eye. Two weeks after the injection, patients noticed improved vision in the injected eye.

Achievements made within the first study prompted an extension in 2009. At that time, Bennett and her husband, Albert Maguire, MD, became interested in administering the injection in patients’ untreated eyes.

“The main concern being that by the initial injection, you are basically vaccinating the person, and if you come along and do a second injection, it’s like a booster effect,” Bennett said. “We certainly didn’t want to have an immune complication, prevent benefit in the second eye and further potentially harm the first eye.”

After continued testing, Maguire injected the untreated eyes of patients from the original study. Ninety days after the injection, the second eye showed improved visual cortex activation.

“That was something that we didn’t expect,” Bennett said. “We realized that one of the things that are different is that by injecting this second eye, the nystagmus is dampened quite a bit.”

Bennett said in an email interview with Ocular Surgery News that a phase 3 clinical trial will be carried out this year, with the hope that the treatment will be approved by the U.S. Food and Drug Administration.

“There is no approved gene therapy drug at this point in time, and so approval of a gene therapy drug by the FDA would be a big step,” she said.

Epiretinal, subretinal implants

The Argus II Retinal Prosthesis System (Second Sight) is an epiretinal implant that is intended to provide electrical stimulation to the retina in order to induce the sensation of visual perception. The Argus II trial is the largest trial of a retinal prosthesis in the United States.

“It’s very important for patients to understand this and for us to understand this, as well: It’s not providing vision in the sense of what we experience,” Jason Hsu, MD, said at the meeting. “This is not color vision. This is not even gray-scale vision. This is the sensation of flickering lights — phosphenes — in a pattern that allows patients to distinguish their surrounding environment.”

Standardized testing was done for visual function and quality of life, including object localization, motion discrimination, visual acuity, orientation and mobility.

Hsu said that the 1- and 2-year postoperative results were similar, with no significant drop-off.

“Using the system, blind subjects were able to detect light and improve their performance on visual tasks. And, the results, again, seem to be sustained long term out to the 2-year results that have been reported here,” he said.

Advancements are also being made on a subretinal implant.

Eberhart Zrenner, MD 

Eberhart Zrenner

Eberhart Zrenner, MD, reported on the subretinal chip implant Alpha IMS (Retina Implant AG) that translates the light distribution of an image at the retinal level and transmits an electric mirror image to the bipolar cells. This allows the patient to have light and shape perception, see up to nine levels of gray, and control contrast and brightness. Many of the 29 patients operated so far can see objects of daily living again, such as a plate and cutlery on a table or door handles; some can even read letters and words, he said.

“We think that we have several advantages with the subretinal implantation,” Zrenner said. “We are replacing the lost retinal photoreceptors by technical ones, and therefore each image point is correctly localized in the visual field. The remaining retinal network can be used for image processing, and objects can be localized simply by eye movements.”

The subretinal implant has no camera outside as the subretinal “camera chip” moves with the eye, whereas the Argus II system requires a camera, a transmitter in a pair of glasses and a small wireless computer.

“The aim is to restore some useful visual functions in patients blind from retinitis pigmentosa. It’s not vision as we are experiencing it right now, but to go from blindness to low vision ability is already a step for somebody who has been blind for many years,” Zrenner said. – by Ashley Biro

  • Bennett J, Ashtari M, Wellman J, et al. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med. 2012;4(120):120ra15.
  • Brown MM, Brown GC, Lieske HB, Lieske PA. Preference-based comparative effectiveness and cost–effectiveness: a review and relevance of value-based medicine for vitreoretinal interventions. Curr Opin Ophthalmol. 2012;23(3):163-174.
  • Humayun MS, Dorn JD, da Cruz L, et al; Argus II Study Group. Interim results from the international trial of Second Sight’s visual prosthesis. Ophthalmology. 2012;119(4):779-788.
  • Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009;374(9701):1597-1605.
  • Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358(21):2240-2248.
For more information:
  • Jean Bennett, MD, PhD, can be reached at Cell and Molecular Biology Graduate Group, 310 Stellar-Chance Labs, 422 Curie Blvd., Philadelphia, PA 19104; 215-898-0915; fax: 215-573-7155; email:
  • Gary Brown, MD, MBA, can be reached at Retina Service, Wills Eye Institute, 840 Walnut St., Suite 1020, Philadelphia, PA 19107; 800-331-6634; email:
  • Jason Hsu, MD, can be reached at Retina Service, Wills Eye Institute, 840 Walnut St., Suite 1020, Philadelphia, PA 19107; 215-928-3300; fax: 215-825-9087; email:
  • Eberhart Zrenner, MD, can be reached at the Center for Ophthalmology, University Eye Hospital, Schleichstraße 12, D-72076 Tübingen, Germany; 49-7071-2984786 or 2987311; fax: 49-7071-295038; email:
  • Disclosures: Bennett, Brown and Hsu have no relevant financial disclosures. Zrenner receives research support from and has a stake in Retina Implant AG.