Subretinal Injection Techniques for Retinal Disease: A Review

Abstract

Inherited retinal dystrophies (IRDs) affect an estimated 1 in every 2000 people, this corresponding to nearly 2 million cases worldwide. Currently, 270 genes have been associated with IRDs, most of them altering the function of photoreceptors and retinal pigment epithelium. Gene therapy has been proposed as a potential tool for improving visual function in these patients. Clinical trials in animal models and humans have been successful in various types of IRDs. Recently, voretigene neparvovec (Luxturna®) has been approved by the US Food and Drug Administration for the treatment of biallelic mutations in the RPE65 gene. The current state of the art in gene therapy involves the delivery of various types of viral vectors into the subretinal space to effectively transduce diseased photoreceptors and retinal pigment epithelium. For this, subretinal injection is becoming increasingly popular among researchers and clinicians. To date, several approaches for subretinal injection have been described in the scientific literature, all of them effective in accessing the subretinal space. The growth and development of gene therapy give rise to the need for a standardized procedure for subretinal injection that ensures the efficacy and safety of this new approach to drug delivery. The goal of this review is to offer an insight into the current subretinal injection techniques and understand the key factors in the success of this procedure.

Three-dimensional heads-up system assisted pars plana vitrectomy and subretinal recombinant tissue plasminogen activator injection for submacular hemorrhage

“…The subretinal injection could cause possible mechanical damage to the retinal nerve fiber layer, RPE, and choroid. Multiple complications with subretinal injections have been reported previously, such as retinal and/or RPE tears, choroidal neovascularization, and so on [ 20 ]. Considering that, minimizing the collateral damage of the injection procedure is extremely important.…”

In Vivo Efficacy and Safety Evaluations of Therapeutic Splicing Correction Using U1 snRNA in the Mouse Retina

“…Fundus imaging was carried out prior to injection on a Phoenix Micron III high-resolution retinal imaging microscope (Phoenix Technology Group, Bend, OR, USA). Subretinal injections were performed by the transcorneal approach [ 39 ]: The cornea was punctured at the nasal side close to or at the limbus with a 30 G cannula, and a 33 G needle attached to a Hamilton microliter syringe (Hamilton, Reno, NV, USA) was inserted through the hole. While the iris may be punctured by this method, touching the lens can be avoided in a free-hand injection as the angle of the injection needle is steep enough to pass it.…”

Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration

“…The region between the RPE layer and the photoreceptors is considered as a subretinal space which allows the direct delivery of drugs to the RPE and photoreceptor cells. The subretinal injections utilize trans-scleral and trans-corneal routes in animal studies for attaining the required desired concentration of a drug in subretinal space [ 113 , 114 ]. It involves the prior conducting of a vitrectomy to separate the posterior vitreous that may use acetonide triamcinolone for better visualization [ 114 ].…”

“…The subretinal injections utilize trans-scleral and trans-corneal routes in animal studies for attaining the required desired concentration of a drug in subretinal space [ 113 , 114 ]. It involves the prior conducting of a vitrectomy to separate the posterior vitreous that may use acetonide triamcinolone for better visualization [ 114 ]. The subretinal injection primarily involves three approaches/routes for the administration of drugs: (a) the transcorneal route crossing through the pupil, lens, vitreous region, and retina; (b) the transscleral route through the limbus region and passing through the vitreous; and (c) the transscleral route crossing through the Bruch’s membrane and choroid [ 114 ].…”

“…It involves the prior conducting of a vitrectomy to separate the posterior vitreous that may use acetonide triamcinolone for better visualization [ 114 ]. The subretinal injection primarily involves three approaches/routes for the administration of drugs: (a) the transcorneal route crossing through the pupil, lens, vitreous region, and retina; (b) the transscleral route through the limbus region and passing through the vitreous; and (c) the transscleral route crossing through the Bruch’s membrane and choroid [ 114 ]. Figure 4 illustrates the approaches for subretinal injection adopted by various researchers for the delivery of drugs for AMD.…”