RU2799076C1 - Method of medicinal products administration into the suprachoroidal space - Google Patents

Abstract

FIELD: medicine; ophthalmology.

SUBSTANCE: fixation ring is placed on the eye, transconjunctival-transcleral injection of the medicinal product into the suprachoroidal space (SCS) through a 30G needle at a distance of 3.5–4 mm posterior to the limbus in the superior temporal quadrant at an angle of 15° to the ocular surface with the direction of the needle in the plane, parallel to the plane of the limbus, with simultaneous pressure on the syringe plunger at the time the needle advances. Before starting the injection, paracentesis of the cornea is performed in the quadrant opposite to the injection site, using a 0.5 ml syringe with a needle 8 mm long. The introduction of the needle into the sclera is performed with a cut facing outward. The moisture of the anterior chamber of the eye is released through paracentesis in a volume of 0.1 ml. Then the medicinal product is injected in a volume of 0.2 ml and after 10 seconds the needle is removed.

EFFECT: invention reduces the risk of intraoperative and postoperative complications and medicinal products reflux from SCS to the ocular surface.

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Description

The invention relates to medicine, namely to ophthalmology, and is intended for the introduction of a drug into the suprachoroidal space.

There are a large number of diseases of the posterior segment of the eye that require long-term and diligent treatment. Currently, intravitreal administration of drugs (glucocorticosteroids (GCS), anti-VEGF, anti-infective) is the main method of delivery for various diseases of the posterior segment of the eye. However, its use is associated with serious side effects such as glaucoma and cataracts. Also, the high frequency of injections and the cost of treatment are burdensome for patients [Kang-Mieler JJ, Rudeen KM, Liu WQ, Mieler WF. Advances in ocular drug delivery systems. Eye (Lond) 2020;34(8):1371-1379].

Recently, the suprachoroidal space (SCS) has emerged as a potential site for drug delivery to the posterior segment of the eye. A number of studies have shown that with suprachoroidal administration, in comparison with intravitreal administration of the drug, 10-12 times higher concentrations of the administered substance are achieved in the sclera, choroid, retinal pigment epithelium, comparable concentrations in the retina and significantly lower concentrations in the vitreous body, iris, ciliary body, lens, and anterior chamber fluid [Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 1996;80(4):332-336]. This increased selectivity could potentially allow a reduction in dosage or frequency of drug administration, as well as a reduction in the risk of cataract formation and/or elevated intraocular pressure (IOP) associated with corticosteroid delivery. The use of corticosteroid injections has shown successful results in a limited range of ophthalmic diseases, including non-infectious uveitis, retinal vein occlusion with macular edema, and diabetic macular edema [Habot-Wilner Z, Noronha G, Wykoff CC. Suprachoroidally injected pharmacological agents for the treatment of chorio-retinal diseases: a targeted approach. Acta Ophthalmol 2019;97(5):460-472].

Access to the SCS is difficult because it is a slit-like space between the choroid and the sclera. Initially, catheters were introduced into this space using a custom hollow microneedle or Hamilton glass syringe [Tyagi P, Kadam RS, Kompella UB. Comparison of suprachoroidal drug delivery with subconjunctival and intravitreal routes using noninvasive fluorophotometry. PLoS One 2012;7(10):e48188.]. These methods are invasive and difficult to perform, with a high risk of postoperative complications.

A known method of suprachoroidal injection of drugs using an injector with microneedles for the introduction of a suspension of triamcinolone acetonide, in which the injection is performed 3.5-4 mm from the limbus in the lower outer quadrant, first the syringe is placed perpendicular to the surface of the eye, then the conjunctiva is compressed with a needle - sleeve no longer than 1 mm and perform a puncture into the sclera until the sleeve stops, after which the drug is slowly injected in a volume of 0.2 ml for 5-10 seconds and the needle is removed (https://clearsidebio.com/technology/scs-microinjector/ ).

The disadvantage of the described method is the high cost and the lack of wide availability of this injector, the high risk of reflux of the drug injected into the SCS due to the short scleral canal at the injection site. There is a risk of injecting the drug into the vitreous cavity in patients with thinned sclera. When the injection is not perpendicular to the surface of the eye, the microneedle of the injector does not pierce through the sclera, and as a result, the drug is injected intrasclerally, and not into the SCS.

The closest analogue of the proposed method is a method of the same purpose, including the use of a 1 ml disposable syringe with a 30G needle and a length of 12.7 mm (Becton Dickinson, Franklin Lakes, NJ, USA). After installing the eyelid expander, the conjunctival cavity is treated with a cotton applicator moistened with povidone-iodine. Then a fixation ring is placed over the eye to prevent its movement. After that, at a distance of 3.5-4 mm posterior to the limbus in the upper temporal quadrant at an angle of approximately 15-20° to the ocular surface, a needle is inserted into the sclera. The bevel of the needle is directed to the surface of the sclera parallel to the limbus. After the bevel of the needle is completely immersed in the sclera, the tip of the needle is redirected back and the insertion of the needle continues. When the needle is inserted, pressure is applied to the plunger of the syringe, which allows the drug to be injected only after the needle tip reaches the SCS. After the injection of 0.1 ml of the drug, the needle is removed immediately after the injection (Zhang DD, Che DY, Zhu DQ. A simple technique for suprachoroidal space injection of triamcinolone acetonide in treatment of macular edema. Int J Ophthalmol 2022; 15(12):2017- 2021).

The disadvantage of this method of suprachoroidal injection is that the use of a 1.0 ml syringe makes it difficult to perform manipulations, increases the inaccuracy of movements, especially at the time of pressure on the syringe plunger, which increases the risk of puncturing the choroid and injecting the drug into the vitreal cavity. The 12.7 mm long 30G needle has insufficient rigidity, thereby reducing the accuracy of the direction of movement of the needle tip when it is inserted into the sclera. This increases the risk of intravitreal administration of the drug and the development of such intraoperative complications as hemophthalmia, suprachoroidal hemorrhage. Rapid withdrawal of the needle immediately after injection increases the reflux of the drug injected into the SCS.

The objective of the claimed invention is to develop an effective method of suprachoroidal injection of drugs for the treatment of diseases of the posterior segment of the eye.

The technical result of the proposed method is to reduce the risk of intraoperative, postoperative complications and reflux of the drug from SCS to the ocular surface.

The technical result is achieved due to the fact that before the start of the injection, paracentesis of the cornea is performed in the quadrant opposite to the injection site, a 0.5 ml syringe with an 8 mm needle is used to administer the drug, and the drug is administered after the liquid is released from the anterior chamber of the eye.

The use of a 0.5 ml syringe for injection into the SCS, in comparison with 1.0 ml, increases the accuracy of manipulation when performed with one hand, and also allows for more controlled pressing of the syringe plunger with one finger due to its shorter exposure to the collected drug from its zero position. The use of an 8 mm 30G injection needle, compared to a 12.7 mm 30G needle, allows more controllable guidance of the needle in the sclera due to greater rigidity. The use of a 30G needle reduces the risk of hemorrhagic complications compared to the use of a larger needle. The introduction of the needle into the sclera with the cut of the end of the needle facing outward makes it possible to accurately visualize the complete immersion of the end of the needle into the sclera, and the timely start of creating pressure on the syringe plunger for drug administration. Performing paracentesis and drainage of anterior chamber moisture allows more drug to be injected into the SCS without the risk of an increase in intraocular pressure, and also reduces the risk of drug reflux from the SCS to the ocular surface. Also, the prevention of reflux of the injected drug from the SCS is to maintain a pause for 10 seconds before withdrawing the needle after drug administration, due to the distribution of the drug in the SCS.

Thus, the claimed method of injection allows the administration of the drug directly into the SCS with great accuracy, and in a larger volume, with a minimal risk of reflux of the drug from the SCS, with a minimal risk of increasing intraocular pressure and hemorrhagic complications.

The method is carried out as follows.

A transconjunctival-transcleral injection of the drug into the SCS is carried out through a 30G needle at a distance of 3.5-4 mm posterior to the limbus in the superior temporal quadrant at an angle of 15° to the ocular surface with the direction of the needle in a plane parallel to the plane of the limbus with simultaneous pressure on the syringe plunger in moment of needle advance. Before starting the injection, paracentesis of the cornea is performed in the quadrant opposite to the injection site. A 0.5 ml syringe with an 8 mm needle is used. The introduction of the needle into the sclera is performed with a cut facing outward. The moisture of the anterior chamber of the eye is released through paracentesis in a volume of 0.1 ml. The drug is injected in a volume of 0.2 ml and after 10 seconds the needle is removed.

After injection of the drug into the SCS, a fundus ophthalmoscopy is performed to ensure that the drug suspension has not been erroneously introduced into the vitreous cavity. Patients were examined using spectral coherence tomography of the anterior segment of the eye (AS-OCT, Casia SS-1000; Tomey, Nagoya, Japan) before and immediately after injection. The control examination was carried out every month after the injection for six months. In total, 30 GCS injections were performed in the SCS by the proposed method in patients with non-infectious macular edema. The results of dynamic observation showed a significant decrease in the central retinal thickness (CRT) after the injection of corticosteroids into the SCS, while maintaining a positive result 4 months after the procedure. In all cases, the drug was injected directly into the SCS. None of the patients had hemorrhagic complications after injection into the SCS. Using the proposed method, it is possible to introduce any drugs into the SCS, depending on the nature of the ophthalmopathology, since the methods of the method do not depend on the characteristics of the drug.

Clinical example 1: patient M., 71 years old, diagnosed with cystic macular edema (Irwin-Gass syndrome), pseudophakia of the right eye. He complained of decreased visual acuity, image distortion. These complaints appeared 1 month after surgery on the right eye, cataract phacoemulsification with intraocular lens implantation. According to optical computed tomography in the macular zone, a change in the macular profile, cystic intraretinal edema, and an increase in CTS to 645 μm were revealed. Ophthalmoscopically in the macular zone, the reflex is smoothed. Visual acuity of the right eye 0.1 is not corrected.

The patient was injected into the SCS according to the proposed method. First, the surgical field was processed in accordance with the general recommendations for intravitreal injection. Then, 0.2 ml of GCS was drawn into a 0.5 ml syringe with a 30G needle 8.0 mm long. Performed paracentesis in the cornea with a knife in the lower-inner quadrant. A fixation ring is installed on the eye. An injection needle was introduced at a distance of 3.5 mm posterior to the limbus in the superior temporal quadrant at an angle of 15° to the ocular surface through the conjunctiva into the sclera with the direction of the needle running parallel to the limbus, with the cut end of the needle facing outward. As the needle was inserted, constant pressure was applied to the plunger of the syringe. Then, moisture was released from the anterior chamber of the eye in a volume of 0.1 ml. After that, 0.2 ml of GCS was injected into the SCS and after 10 seconds the needle was removed.

Immediately after the injection, an ophthalmoscopy of the fundus was performed, in which no GCS was detected in the vitreal cavity, and in the upper outer quadrant at the extreme periphery, a local protrusion of the choroid in the form of a hemisphere no more than 3 mm high was detected. In the early postoperative period, there was no increase in intraocular pressure and hemorrhagic complications. At a follow-up period of 1 month, according to optical computed tomography, the macular profile was normalized, there was no cystic edema, and the CTS was 268 μm. Visual acuity of the right eye was 0.8 with correction.

Clinical example 2: patient S., 45 years old, diagnosed with cystic macular edema, non-infectious uveitis, phacosclerosis of the left eye. She complained of decreased visual acuity, image distortion, floating flies in front of the eye. The patient has a history of rheumatoid arthritis. According to optical computed tomography in the macular zone, a change in the macular profile, cystic intraretinal edema, and an increase in CTS up to 580 μm were revealed. Ophthalmoscopically in the vitreal cavity, the destruction of the vitreous body, in the macular zone, the reflex is smoothed. Visual acuity of the right eye 0.2 is not corrected.

The patient was injected into the SCS according to the proposed method. First, the surgical field was processed in accordance with the general recommendations for intravitreal injection. Then, 0.2 ml of GCS was drawn into a 0.5 ml syringe with a 30G needle 8.0 mm long. Performed paracentesis in the cornea with a knife in the lower-inner quadrant. A fixation ring is installed on the eye. An injection needle was introduced at a distance of 4 mm posterior to the limbus in the upper outer quadrant at an angle of 15° to the ocular surface through the conjunctiva into the sclera with the direction of the needle travel parallel to the limbus, with a cut of the end of the needle facing outward. As the needle was inserted, constant pressure was applied to the plunger of the syringe. Then, moisture was released from the anterior chamber of the eye in a volume of 0.1 ml. After that, 0.2 ml of GCS was injected into the SCS and after 10 seconds the needle was removed.

Immediately after the injection, an ophthalmoscopy of the fundus was performed, in which no GCS was detected in the vitreal cavity, and in the upper outer quadrant at the extreme periphery, a local protrusion of the choroid in the form of a hemisphere no more than 3 mm high was detected. In the early postoperative period, there was no increase in intraocular pressure and hemorrhagic complications. At a follow-up period of 1 month, according to optical computed tomography, a positive trend was revealed in the reduction of cystic intraretinal edema and a decrease in CTS to 300 μm. Visual acuity of the right eye was 0.5 with correction. At a follow-up period of 6 months, according to optical computed tomography, there was no negative dynamics in the increase in cystic intraretinal edema in comparison with the results one month after the injection. The PZT remained at the same level of 303 µm. Visual acuity of the right eye was 0.5 with correction. There were no lens opacities or increased intraocular pressure.

Thus, the claimed method of injection allows the administration of drugs directly into the SCS with great accuracy and in the required amount, with a minimal risk of drug reflux from the SCS, with a minimal risk of increasing intraocular pressure and hemorrhagic complications. It also shows good clinical results in the treatment of various diseases of the posterior segment of the eye with minimal cataractogenic effect.

Claims (1)

The method of drug administration into the suprachoroidal space (SCS), including the installation of a fixation ring on the eye, transconjunctival-transcleral administration of the drug into the SCS through a 30G needle at a distance of 3.5-4 mm posterior to the limbus in the superior temporal quadrant at an angle of 15° to the ophthalmic surface with the direction of the needle in a plane parallel to the plane of the limbus, with simultaneous pressure on the syringe plunger at the moment the needle advances, characterized in that before the injection, corneal paracentesis is performed in the quadrant opposite to the injection site, a 0.5 ml syringe with a needle length is used 8 mm, the needle is inserted into the sclera with a cut facing outward, the moisture of the anterior chamber of the eye is released through paracentesis in a volume of 0.1 ml, then the drug is injected in a volume of 0.2 ml and the needle is removed after 10 seconds.