RU2835865C1 - Method of administering drug into suprachoroidal space of eyeball - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to ophthalmology. Drug is introduced into the suprachoroidal space, the corneal paracentesis is performed on the opposite side of the injection site with the release of moisture of the anterior chamber in volume of 0.1 ml, using 0.5 ml syringe with 30G needle, which is introduced transconjunctival-transscleral in the upper temporal quadrant at angle of 15° to the eye surface with the needle travel direction in the plane parallel to the limb plane. Preparation is introduced in volume of 0.2 ml, then the needle is removed 10 seconds later. Thickness of the patient’s eye membranes in the area of injection is measured by optical coherence tomography in micrometres. Then, a limiter with a fixture is put on an injection needle of the insulin syringe with medicinal substance, the cutting angle of the fixture coincides with the cutting angle of the needle, leaving the needle tip by a value according to measurement of thickness of eye membranes in micrometres. Eye is fixed with microtweezers in the limb area, the needle is inserted at distance of 1 to 4 mm from the limb with a cut inside until the limiter touches the eyeball surface, and then the syringe plunger is pressed.

EFFECT: method provides more accurate positioning of the needle tip in the suprachoroidal space, improves the control of the drug administration, reduces the probability of eye membrane injury and increases the effectiveness of the drug administration into the suprachoroidal space.

1 cl, 2 ex, 6 dwg

Description

The invention relates to medicine, in particular to ophthalmic surgery, namely to methods of delivering a medicinal product to the tissues of the posterior part of the eye.

Among the traditional methods of administering drugs to the eye tissues, there are instillations of drops, subconjunctival or subtenal injections, parabulbar and retrobulbar injections, and electrophysiological methods of drug delivery. However, none of the listed methods achieved a sufficient concentration of the drug in the posterior segment of the eye, namely in the retina and choroid, due to the low permeability of the hematoophthalmic barrier [Egorov A.E. et al. 1997]. Methods of transconjunctival cryoapplication or laser coagulation of the sclera [Patent of the Russian Federation No. 2149615, Nesterov A.P., et al.] were proposed to increase the bioavailability of drugs, but all of them required additional equipment, increased the likelihood of complications associated with iatrogenic eye injury, and the development of inflammation.

Administration of ophthalmic drugs into the space between the sclera and choroid of the eyeball, known as the suprachoroidal space, is a relatively new method of drug delivery that is actively undergoing preclinical and clinical studies (Chen et al., 2015; Einmahl et al., 2002); Gilger et al., 2013; Goldstein, 2015; Yanchulev, 2014; Olsen et al, 2006; Patel et al., 2012; Patel et al., 2011). In contrast to the traditional methods of ophthalmic drug administration described above, suprachoroidal injections provide targeted drug delivery to the choroid and retina with high bioavailability. (Abarca et al., 2013; Chen et al., 2015; Einmahl et al., 2002, Kadam et al., 2013, Olsen et al., 2011; Patel et al., 2012; Patel et al., 2011; Peden et al., 2011, Tzameret et al., 2014). Thus, the administration of corticosteroids by suprachoroidal administration, in particular triamcinolone for the treatment of diabetic macular edema, more than halves the number of injections performed, compared with intravitreal injections of dexamethasone, due to the accumulation of high concentrations in the retina of the posterior segment of the eye [Haroon Tayyab, et al, 2020]. In addition, suprachoroidal triamcinolone injections reduce the likelihood of developing lens opacity and the risk of developing glaucoma [Campochiaro P.A, Wykoff S.S., Brown D.M., et al., 2017]. Currently, clinical trials are evaluating the safety and effectiveness of injections in diseases such as posterior non-infectious uveitis [Goldstein, 2015] and can even be performed on an outpatient basis [Jiang et al., 2007; Patel et al., 2012; Patel et al., 2011].

Among the methods of delivering a medicinal substance to the posterior part of the eyeball, a method of subscleral administration of medicinal preparations is known (RU Patent No. 2238709 dated 12.20.2004). The method consisted of a perpendicular puncture with an injection needle from an insulin syringe to a depth of 1 mm in the lower-outer segment, closer to the posterior pole of the eyeball of its surface through the conjunctiva, the outer and inner leaflets of the Tennon capsule under the episcleral flap and the medicinal preparation was administered. To prevent damage to the eye structures and prevent complications, a limiter in the form of a disk of compacted tissue was installed at the end of the injection needle, at a distance of 1 mm. A significant disadvantage of this method is the localization of the injection, where there is a high risk of retinal injury, the risk of a through puncture of the sclera if the thickness of the eye membranes is less than a specified value.

A method for delivering a medicinal substance directly into the suprachoroidal space is also known (patent No. 2635320 Prausnitz Mark R., Edelhauser Henry F., Patel Samirkumar Rajinikanth, published 10.11.2017 Bulletin No. 31), where it was proposed, in addition to perpendicular insertion of the needle to the surface of the eye, to insert the needle at different angles, while the effective length of the needle can vary, reaching a length of up to 2000 μm or 2 mm. The advantage of this method is a reduction in the risk of developing endophthalmitis when performing a puncture of the sclera at an angle. However, it should be noted that the disadvantages are that the depth of penetration of the microneedle is visually controlled during the injection. At the same time, the authors emphasize that the depth of microneedle insertion can be controlled by measuring the degree of tissue deformation, which is not accurate and may depend on the thickness of the membranes, the elastic properties of the membranes of the eye, the level of intraocular pressure, and makes it extremely difficult to perform the injection.

The closest in technical essence and achieved result is the method of introducing a medicinal product into the suprachoroidal space, which includes installing a fixation ring on the eye, performing corneal paracentesis on the side opposite to the injection site with the release of 0.1 ml of aqueous humor from the anterior chamber of the eye, using a 0.5 ml syringe with an 8 mm long and 30G diameter needle, which is inserted transconjunctivally-transclerally with the cut facing outward, 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 and simultaneously pressing on the syringe plunger at the moment of needle advancement, the drug is injected in a volume of 0.2 ml, then after 10 seconds the needle is removed (patent No. 2799076 dated 03.07.2023 Bulletin No. 19.).

Despite all the advantages of the known method of introducing a medicinal preparation into the suprachoroidal space, taken as a prototype, it is necessary to note the disadvantages: the thickness of the eye membranes through which the needle is inserted is not taken into account, namely: the thickness of the sclera, conjunctiva and Tennon's membrane at the site of needle insertion, which significantly affects the final position of the needle tip with the hole, and also the gradual introduction of the preparation when advancing the needle with the bevel outward reduces the probability of delivering the medicinal substance directly into the suprachoroidal space and increases the risks of introducing the medicine into the thickness of the sclera or episclerally.

The technical result, which is aimed at achieving by creating this invention, is to increase the accuracy of the placement of the needle tip in the suprachoroidal space, improve control of the introduction of the medicinal substance, reduce the likelihood of injury to the membranes of the eye and increase the efficiency of the introduction of the medicinal preparation into the suprachoroidal space.

The stated technical result is achieved by the fact that in the method of introducing a medicinal preparation into the suprachoroidal space, which includes performing a corneal paracentesis on the opposite side from the injection site with the release of 0.1 ml of the anterior chamber fluid of the eye, using a 0.5 ml syringe with a 30G diameter needle, which is inserted transconjunctivally-transclerally 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, the preparation is introduced in a volume of 0.2 ml, then after 10 seconds the needle is removed, characterized in that the thickness of the patient's eye membranes in the injection area is measured using optical coherence tomography in micrometers, then a limiter with a lock is put on the injection needle of the insulin syringe with the medicinal substance, the cutting angle of which coincides with the cutting angle of the needle, leaving the tip of the needle at a value according to the measurement of the thickness of the eye membranes in micrometers, the eye is fixed Using microtweezers in the limbus area, insert the needle at a distance of 1 to 4 mm from the limbus with the cut inward until the stopper touches the surface of the eyeball and then press the plunger of the syringe.

Fig. 1 shows a diagram of the implementation of the proposed method of introducing a drug into the suprachoroidal space, where:

1 - suprachoroidal space

2 - sclera

3 - conjunctiva and tennoid membranes of the eyeball

4 - needle stop

5 - needle lock

6 - injection needle 30G

7 - insulin syringe with medicinal substance

8 - syringe plunger

The method is carried out in several stages.

The first step is to measure the thickness of the patient's eye membranes (3) in the injection area using optical coherence tomography in micrometers (Fig. 2).

In the second stage, a limiter (4) with a retainer (5) is put on the injection needle (6) of the insulin syringe with the medicinal substance (7), the bevel angle of which coincides with the bevel angle of the needle, leaving the tip of the needle at a value according to the measurement of the thickness of the eye membranes (2 and 3), then the eye is fixed with microtweezers in the limbus area, a corneal paracentesis is performed on the opposite side from the injection site with the release of 0.1 ml of the anterior chamber fluid of the eye and a transconjunctival-transcleral puncture is performed 1-4 mm from the limbus, in the upper temporal quadrant at an angle of 15° to the ocular surface with the direction of the needle in the plane, with the bevel of the needle inward, until the limiter touches the surface of the eyeball, then the plunger of the syringe (8) is pressed and 0.2 ml of the medicinal substance is injected and the needle is removed after 10 seconds.

After the injection is completed, antiseptic drops are instilled.

The advantages of the proposed invention are that the location of the needle tip is at a depth that is measured in advance on an optical coherence tomograph, and the limiter with the needle lock allows for the injection to be performed safely, effectively and most accurately to introduce the drug into the suprachoroidal space.

Using the proposed method, 32 operations were performed on patients with macular edema aged 62 to 78 years.

Clinical example 1. Patient A., 72 years old, underwent combined surgical treatment of cataract phacoemulsification with intraocular lens implantation, vitrectomy, membrane peeling, with air injection for epimacular fibrosis with vitreomacular traction syndrome. Three months after the surgery, macular edema up to 476 μm in height was diagnosed according to optical coherence tomography, visual acuity was 0.8. The drug triamcinolone was administered according to the proposed method of the invention at a distance of 4 mm from the limbus. Seven days after the surgery, the height of the macular edema decreased to 370 μm. Dynamic observation showed a decrease in the thickness of the macular edema after 6 months to 345 μm, an improvement in visual acuity to 1.0 (Fig. 3, 4).

Clinical example 2. Patient V., 1 year old, diagnosed with congenital operated terminal glaucoma, partial congenital cataract, sluggish uveitis, macular edema. Before the operation, the ultrasound scan showed the thickness of the macular edema to be up to 1.2 mm. Surgical treatment was performed according to the proposed method - suprachoroidal injection of triamcinolone 1 mm from the limbus. After the operation, the height of the macular edema decreased to 0.5 mm, after 6 months to 0.5 mm (Fig. 5, 6).

Claims (1)

A method for administering a medicinal product into the suprachoroidal space, comprising performing a corneal paracentesis on the opposite side from the injection site with the release of 0.1 ml of anterior chamber fluid, using a 0.5 ml syringe with a 30G diameter needle, which is inserted transconjunctivally-transclerally 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 limbus plane, administering the drug in a volume of 0.2 ml, then removing the needle after 10 seconds, characterized in that the thickness of the patient's eye membranes in the injection area is measured using optical coherence tomography in micrometers, then a limiter with a lock is put on the injection needle of an insulin syringe with a medicinal product, the bevel angle of which coincides with the bevel angle of the needle, leaving the tip of the needle at a value according to the measurement of the thickness of the eye membranes in micrometers, fixing the eye with microtweezers in the limbus area, administering the needle at a distance of 1 to 4 mm from the limbus with the cut inward until the stopper touches the surface of the eyeball and then press the plunger of the syringe.