The Role of Subretinal Injection in Ophthalmic Surgery: Therapeutic Agent Delivery and Other Indications

Abstract

Subretinal injection is performed in vitreoretinal surgery with two main aims, namely, the subretinal delivery of therapeutic agents and subretinal injection of fluid to induce a controlled and localized macular detachment. The growing interest in this technique is mainly related to its suitability to deliver gene therapy in direct contact with target tissues. However, subretinal injection has been also used for the surgical management of submacular hemorrhage through the subretinal delivery of tissue plasminogen activator, and for the repair of full-thickness macular holes, in particular refractory ones. In the light of the increasing importance of this maneuver in vitreoretinal surgery as well as of the lack of a standardized surgical approach, we conducted a comprehensive overview on the current indications for subretinal injection, surgical technique with the available variations, and the potential complications.

Keywords: drug delivery; full-thickness macular hole; gene therapy; submacular hemorrhage; subretinal fluid application; subretinal injection; tissue plasminogen activator.

Figure 1

Subretinal gene therapy. Subretinal injection of gene therapy in a patient with retinitis pigmentosa and RPE-65 mutation. Injection site was placed along the supero-temporal vascular arcade. The injection, fovea-involving, was performed automatically, keeping a controlled injection pressure to avoid the overstretching of the retina and, in particular, of the fovea.

Figure 2

Schematic diagram of “lock and load” or a “load and lock” method to load the therapeutic agent. On the left “lock and load” (A) schematic illustration of viscous fluid injection mode (VFIM) syringe and subretinal cannula; (B) cannula and VFIM syringe for subretinal injection are assembled; (C) the vector solution is aspirated from the vial. On the right “load and lock” (A) the vector solution is aspirated using a separate syringe; (B) the vector is then transferred from the first syringe into the distal end of the VFIM syringe; (C) VFIM and subretinal cannula are assembled; (D) the system is ready for use.

Figure 3

Subretinal injection for full-thickness macular hole: (A) schematic diagram of fundus with full-thickness macular hole; (B) injection of perfluorocarbon liquid until the edges of the hole are covered; (C) three subretinal blebs of BSS created using a subretinal cannula in different macular quadrants; (D) once PFCL is removed, the bubbles are further enlarged to involve the hole center.

Figure 4

Atrophic changes after gene therapy. (A) Baseline; (B) 1 year after subretinal injection of voretigene neparvovec-rzyl, peripapillary area of chorioretinal atrophy; (C) 2 years after subretinal injection of voretigene neparvovec-rzyl, further enlargement of peripapillary chorioretinal atrophy.