Expert shares tips for safe subretinal delivery of gene therapy
FORT LAUDERDALE, Fla. — Best practices for safe subretinal delivery of gene therapy were presented at the Retina World Congress.
“We have been continually looking at refining the technique and improving safety by avoiding excessive stretching of the retina, macular hole formation, reflux, hemorrhage and injury to the retinal pigment epithelium (RPE), as well as postoperative complications such as hypotony and inflammation,” Andreas K. Lauer, MD, said. Lauer is a specialist who has performed gene therapy in 160 patients for 12 different conditions, mostly by subretinal injection.
Over the years, he has transitioned from direct manual delivery to pneumatic-assisted injection using the Constellation vision system (Alcon) and intraoperative OCT.
His first recommendation was to direct the infusion cannula to the mid-periphery, away from the bleb area. Triamcinolone is important to remove the hyaloid so that it does not get trapped into the injection needle. In eyes in which the separation is difficult, using a loop or a scraper may be helpful.
Long, flexible needles are advantageous in many ways, according to Lauer.
“The moment you see a bow, you know you have gone far enough to start injecting. This prevents you from puncturing the RPE and choroid. As the bleb develops, having that longer metal end allows you to stay in the bleb, and you are less likely to dimple it,” he said. “The other thing I do is scleral depression before the injection to avoid deformation of the bleb by fluid currents. This is more relevant for larger blebs.”
Rapid injection speed of 1,800 µL per minute results in loss of RPE signal and possibly retinal damage. Lauer recommended an injection rate of 180 µL per minute or less. Injection pressure is monitored by the Constellation system.
“I use a [balanced salt solution] bleb first and then propagate the bleb as a second step with the aid of OCT, with a maximum pressure of 16 psi. Take into account that the older the patient is, the less pressure is needed to separate the neurosensory retina,” he said.
In his hands, injections are taking mostly 2 to 6 minutes at less than 180 µL per minute.
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Lauer AK. Best practices in retinal gene therapy surgery. Presented at: Retina World Congress; May 12-15, 2022; Fort Lauderdale, Fla.
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