Suprachoroidal injection (SC) is an innovative drug delivery method that has the potential to greatly revolutionize the field of ophthalmology. In fact, this technique has shown to possess many advantages over certain traditional routes of administration such as its simplicity as well as its ability to bypass biological barriers. Notably, access to the SCS can be achieved using microcatheters, needles, or microneedles. Each technique has its own benefits and drawbacks, but so far, microneedle-based injections offer precise control, broad coverage, and improved safety compared to standard needles, making them the most promising route for drug administration.
1. Rationale
SC injection is a minimally invasive and potentially long-lasting treatment method that combines the benefits of IV and subretinal injections [1][2][59,63]. The suprachoroidal space (SCS) can be accessed using various tools, including catheters, needles, and microneedles. Microneedles offer improved precision and control during in-office deliveries to the SCS compared to traditional hypodermic needles [1][59].
1.1. Advantages over the Intravitreal Injection
SC injection provides precise and targeted delivery to the retina, retinal pigment epithelium (RPE), and choroid, bypassing barriers encountered in intravitreal (IV) drug administration [3][64], resulting in broader bioavailability across the diseased retina and choroid [1][2][59,63].
The compartmentalization within the subconjunctival space (SCS) plays a key role in the advantages of SC injection. It restricts drug exposure to target tissues, minimizing contact with the anterior segment and reducing complications like cataract formation and elevated intraocular pressure [4][24]. Additionally, it decreases systemic absorption, leading to fewer systemic side effects [4][24]. A 2022 study in rabbits demonstrated that SC delivery of TRIESENCE provided 12-fold greater exposure to the RPE, choroid, sclera, and retina compared to IV delivery, while significantly reducing drug exposure to anterior chamber structures by 460-fold, 34-fold, and 22-fold for the lens, iris ciliary body, and vitreous humor, respectively [4][24].
SC injection offers sustained release, reducing the need for frequent injections and patient appointments [1][59]. It also theoretically poses a lower risk of endophthalmitis compared to IV injections, although further studies are needed to confirm this claim [4][24]. Moreover, risks associated with direct vitreous cavity injections, such as traumatic cataracts and retinal tears leading to detachments, may be diminished. SC injection also mitigates visual axis obstruction and reduces post-injection floaters, a common side effect with IV methods [1][59].
1.2. Advantages over Subretinal Injection
The SC method, compared to subretinal injection, offers the advantage of being administered in an outpatient setting, eliminating the need for complex surgical procedures like vitrectomy [1][2][59,63]. Additionally, it has the potential to provide a broader distribution of drugs throughout the posterior segment [3][64].
1.3. Drug Suspension Size and Formulation Viscosity
Current research is investigating the possibility of modifying drug suspension size and formulation viscosity to customize the duration and distribution of injected drugs. This flexibility offers the potential for precise tailoring of drug delivery, ensuring the appropriate amount of medication reaches the intended target location.
1.4. Cost-Effectiveness
A 10-year simulated US adult patient-level model assessed the cost-effectiveness of suprachoroidal triamcinolone acetonide (SC-TA) compared to best supportive care for macular edema derived from the PEACHTREE trial. The study found that SC-TA was a cost-effective procedure at willingness-to-pay thresholds of $50,000 or more per quality-adjusted life-year gained [5].
The combination of practicality, enhanced safety profile, proven efficacy, targeted delivery, and durability offered by SC drug delivery has positioned SC injections as an innovative treatment approach for various ocular conditions. This highlights the need for further research into this therapeutic strategy.
Access to the SCS can be achieved through three primary methods: microcatheters, needles, and microneedles. The iTrack microcatheter, for example, involves inserting a 250 A microcatheter into the SCS through a scleral incision [6][65]. The microcatheter's placement is guided and adjusted using indirect ophthalmoscopy, allowing for precise targeting and visualization with the assistance of a flashing diode [7]. However, this invasive procedure typically requires an operating room and relies on the administrator's skills. Potential risks and complications include vitreous penetration, SC hemorrhage, choroidal tears, irregularities in choroidal blood flow, post-operative inflammation, scleral ectasia, retinal detachment, wound abscess, and endophthalmitis [7].
Alternatively, injection into the SCS can be performed using a free-hand technique with a standard hypodermic needle attached to a Hamilton syringe or insulin syringe [7][8][9][7,66,67]. The needle is inserted behind the limbus of the sclera, either with or without sclerotomy, and advanced slowly and controlledly by applying gentle plunger pressure. The injection is administered gradually upon experiencing a loss of resistance. This technique offers the advantage of using readily available materials and being less invasive, making it more accessible and convenient. However, it lacks visualization capabilities and requires extensive training and skill to ensure precise injection. There is a risk of unintended injections into structures, leading to complications such as choroidal hemorrhage and retinal detachment. The difficulty in controlling insertion depth and angle further increases the likelihood of inadvertent intravitreal or subretinal injections.
Hollow microneedles, commonly used for transdermal drug delivery, have a significant impact on accessing the subconjunctival space (SCS) without the need for surgical procedures [7][10][7,13]. These miniature devices feature a hollow internal compartment filled with drug dispersion or solution, along with small-holed tips. Recent advancements in microneedle technology have made SCS accessibility more convenient. One such innovation is the SCS microinjector, a manual piston syringe designed for non-surgical access to the SCS [11][68]. It comes with varying microneedle lengths (900 µm or 1100 µm) to accommodate different scleral thicknesses. The microneedle is inserted until a loss of resistance is felt, with its length slightly exceeding that of the scleral and conjunctival layers to minimize the risk of vitreous perforation [11][68].
The process of drug administration using the SCS microinjector involves several steps. After local anesthesia, a 900 µm microneedle is positioned perpendicularly 4.5 mm posterior to the limbus at the pars plana. Gentle pressure is applied to create a sealing gasket between the needle hub and conjunctiva, preventing backflow. The injection into the SCS takes place over 5–10 seconds while maintaining the perpendicular position and compressing the conjunctiva. After the injection, the needle hub should remain in place for 3 to 5 seconds. If there is still scleral resistance, an 1100 µm microneedle should be used instead [12][69].
Microneedle technology allows precise control in reaching the SCS, distinguishing it from standard hypodermic needles [7][10][7,13]. The use of short microneedles ensures consistent penetration into the SCS, facilitating drug delivery to the intended site. Once inside the SCS, the injectate spreads broadly in a posterior and circumferential manner, ensuring comprehensive coverage. Unlike catheter-based procedures, microneedle-based SC injections can be performed in an office setting under aseptic conditions, without the need for vitrectomy or sclerotomy. These SCS microneedles are specifically designed to match the approximate thickness of the sclera, offering several advantages such as ease of use, minimal pain, affordability, low invasiveness, reduced training requirements, outpatient suitability, and an improved safety profile. Consequently, they represent the most promising approach for drug administration [7][10][7,13].
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