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Invited Commentary
February 2, 2017

Visual Consequences of Delivering Therapies to the Subretinal Space

Author Affiliations
  • 1Department of Ophthalmology, University of California–San Francisco
JAMA Ophthalmol. Published online February 2, 2017. doi:10.1001/jamaophthalmol.2016.5659

Inherited retinal degenerations represent some of the most challenging diseases that ophthalmologists and affected patients encounter. They cause progressive, relentless vision loss as a result of changes in genes that are critical to the survival of photoreceptors and retinal pigment epithelial (RPE) cells. To make matters worse, the primary cells affected by the degeneration are isolated from the rest of the systemic circulation by the blood-retina barrier, making delivery of therapies to these cells extremely challenging. The most direct delivery method is to create a retinal detachment and deliver the treatment to the subretinal space between the retina and RPE cells. In general, detachment of the photoreceptors from the RPE cells causes vision loss, as documented in many studies of the consequences of macula-off rhegmatogenous retinal detachment and its incomplete visual recovery after repair.1 This detachment is especially of concern in eyes with retinal degeneration. However, to avoid exposing the eye and the rest of the body to extremely high doses of therapies required to deliver treatment to the photoreceptors, investigators have justified creating iatrogenic retinal detachment to deliver effective titers of viral vectors and stem cells to the subretinal space, with the goal of effectively treating photoreceptors and RPE cells.

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