Surgical “pearls” of research have been published in the journal, Retina (accessed January 18, 2021), following the completion of 120 subretinal surgeries, performed by a two-surgeon team based at the Department of Ophthalmology, Bascom Palmer Eye Institute at the University of Miami. Similarly, there are other surgical teams across the EU and several other jurisdictions to develop further expertise in this particular field. Given that an increasing number of surgical treatments may derive from a range of multiple gene therapies, this current study has provided some valuable insights to support retinal surgeons across other centres. The report concluded that surgical techniques evolve “as surgeons are exploring ways to minimize trauma to the retina while delivering the correct dose of the virus to the desired treatment target zone”. At current estimates, clinical trial databases indicate that there are more than 45 trials focused on gene therapy studies for inherited retinal degenerations.
The study has reported 120 subretinal cases focused on choroideremia, achromatopsia, retinitis pigmentosa, RPGR and for the approval of voretigene neparvovec-rzyl (licensed by EMA and FDA). Several pearls to be outlined from their current observations range from actual surgical techniques (including video links in the paper), to managing of the reflux vector for visualisation and the optimisation of supporting OCT to identify the site location for delivery of the vector. The posterior hyaloid in patients with IRDs may be abnormal and therefore staining with dilute triamcinolone acetonide improves visualization. The researchers have advised that, “in many patients with peripheral retinal atrophy, the hyaloid elevates poorly anterior to the equator. To avoid peripheral breaks, we stop elevating when we notice retinal traction or strong adhesion”. In addition, site selection for the injection is a key step of the surgery allowing targeting along the superior temporal or inferior temporal arcade. Vascular landmarks help “to locate the self-sealing penetration site if multiple injections into the same retinotomy are administered, such as virus after BSS or multiple pulses”. In terms of intraoperative OCT, imaging has been an extremely helpful tool to confirm subretinal versus suprachoroidal injection, providing “real-time assurance that the target zone has been elevated, and allows monitoring the foveal stretch”.
Commenting on their assessments, researchers highlighted that other subretinally-delivered gene products “may become commercially available in the near future with more surgeons performing gene therapy surgery. Improvements in vector design may facilitate exposure of subretinal target tissues with alternative routes of administration, such as intravitreal or suprachoroidal injection. Nonetheless, lessons learned during current subretinal gene therapy cases will remain relevant to other targeted subretinal therapies such as cellular transplantation or retinal prostheses”.