RU2696923C1 - Method for surgical management of subretinal hemorrhages - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine, specifically to ophthalmology. For surgical treatment of subretinal hemorrhages of various aetiologies complicating the course of age-related macular dystrophy with the subretinal neovascular membrane, subtotal vitrectomy is performed with removal of the posterior hyaloid membrane, introduction of recombinant prourokinase solution into subretinal space together with air bubbles, for this purpose retinal fibers are stratified with the above solution flow; at that, internal boundary membrane is locally removed in area of lamination.EFFECT: method enables improving the functional results of the surgical intervention, reducing the risk of postoperative complications, reducing the risk of developing retina detachment, by translocation of blood from the central area and resorption thereof with direct contact with the drug substance.3 cl, 3 ex, 16 dwg

Description

The invention relates to medicine, and specifically to ophthalmology, and is intended for the surgical treatment of subretinal hemorrhages (IBS) of various etiologies, complicating the course of age-related macular degeneration with a subretinal neovascular membrane (SNM).

Subretinal hemorrhage is a complex pathology that occurs in the retina. In this case, damage to medium or large vessels occurs. Such a disease can be the result of a persistent increase in blood pressure, pathological processes in the vessels, metabolic disorders, age-related macular degeneration, with eye injuries. Such types of bleeding quite often affects only one eye. The resulting submacular hemorrhage is always accompanied by a significant decrease in visual acuity. Significant damage to the functional state of the retina is caused by iron oxide formed during the breakdown of hemoglobin, causing toxic damage to the retina and pigment epithelium. The prolonged presence of a clot under the retina is accompanied by its contraction with mechanical damage to photoreceptors. Subsequently, the fibrin clot is converted into fibrous tissue with necrosis of the adjacent retina, which is accompanied by an irreversible loss of function. This dictates the need for early removal of submacular hemorrhage.

The development and improvement of microinvasive vitreous surgery has contributed to the development of active approaches to the treatment of IBS. The greatest interest today is the use of fibrinolytic enzymes with their introduction intravitreal or subretinal. The mechanism of action of these drugs is the conversion of plasminogen to plasmin, which allows you to lyse a clot and, depending on the surgical technique, remove or deploy it from the macular zone. In Western countries, tissue plasminogen activator is used. In Russia, proenokinase (hemase) proenzyme is common.

Age-related macular degeneration takes third place after glaucoma and diabetic retinopathy among the causes of blindness in the second half of life. Against the background of an increase in the life expectancy of the population, the problem of age-related macular degeneration becomes very relevant. The loss of central vision and the loss of general disability give this pathology great social and medical significance. In 80-90% of cases, serious central vision loss is associated with the formation of SNM in the central zone of the retina. Quite often, they are complicated by the appearance of submacular hemorrhage, which additionally has a toxic effect on the sensitive neurosensory retina and significantly reduces the chances of restoration of vision.

Among surgical techniques for blood dislocation from under the central region of the retina are known: vitrectomy with intravitreal administration of a tissue plasminogen activator, isolated pneumodislocation, YAG - laser retinopuncture, submacular surgery, combined use of gas and tissue plasminogen activator. The essence of these interventions is to more fully remove blood clots from the central region to reduce the toxic effect of hemolysis products on photoreceptors and prevent the development of submacular proliferation.

There is a method of surgical treatment of submacular hemorrhages by intravitreal administration of expanding gas and tissue plasminogen activator without resorting to vitrectomy (Heriot W. Intravitreal gas and tPA: an outpatient procedure for submacular hemorrhage. Presented at: Meeting of the American Academy of Ophthalmology; Chicago: Octouber 1996 ; Chen C. Management of submacular hemorrhage with Intravitreal injection of tissue plasminogen activator and expansile gas. Retina 2007; 27: 321-328). It consists in the slow intravitreal administration of a diluted solution of tissue plasminogen activator (TAP) through a flat part of the ciliary body at a dose of 100 mg / 0.1 ml and 0.3-0.4 ml of perfluoropropane gas (C ₃ F ₈ ) or sulfurhexafluoride (SF ₆ ) For two days, the patient observes a downward facing position. The contact of a blood clot with TAP leads to its partial lysis and displacement under the action of gas from the macular region to the lower half of the retina.

The disadvantage of this method is the lack of impact on the etiological component of subretinal hemorrhage: directly on the subretinal neovascular membrane. Surgical intervention leads only to anatomical dislocation of blood from the central region, reducing its toxic effect on the retina, without affecting the visual prognosis, and the functional results of the operation are usually limited by the presence of a subretinal neovascular membrane in the macular zone. The introduction of an expanding gas without preliminary vitrectomy leads to a change in the structure of the vitreous, provokes the onset of a proliferative process, which can cause retinal detachment (according to different authors, from 3 to 36% of cases).

A known method of treating massive submacular hemorrhage (patent RU No. 2342105, IPC A61F 9/007, A61K 38/43, A61K 38/49, A61P 27/02, published: 12/27/2008 Bull. No. 36, in which subtotal vitrectomy is performed. After Removal of the vitreous body perform retinotomy over hemorrhage and fill the vitreous cavity with air A solution of recombinant prourokinase “hemase” in the amount of 0.3-0.5 ml of 1500-2000 ME for 15-20 minutes is injected into the retina in the projection of the hemorrhage and the liquid fraction is evacuated blood from under the retina. Wash the remnants of the drug. In case of incomplete After blood removal from under the retina, the vitreous cavity is re-filled with air and recombinant prourokinase is reintroduced in the same volume of 500-1000 ME. Air is replaced with gaseous organofluorine compound. After surgery, the patient is placed in the “on the back” position for 2 hours, and then in the "face down" position for 1-3 days. The method allows for the full and accelerated lysis of the fibrin clot, which forms the basis of hemorrhage, which helps to stop the mechanical effects of fibrin and eliminate toxic the influence of the products of decay of blood cells in the neuroepithelium and the retinal pigment epithelium while minimizing mechanical trauma to the retina during surgery.

A known method for the surgical treatment of subretinal hemorrhages on the background of age-related macular degeneration with a subretinal neovascular membrane (patent RU No. 2366388, IPC A61F 9/00, A61K 39/395, A61K 35/16, A61K 38/49, A61P 27/02, published: 10.09. 2009 Bull. No. 25, adopted as a prototype in which subtotal vitrectomy is performed with the posterior hyaloid membrane removed. Bevacizumab or ranibizumab is intravitreal, tissue plasminogen activator and expanding gas are introduced intravitreal, followed by face down positioning of the patient. dislocate blood from under the retina, exert a pathogenetic effect on the source of hemorrhage, prevent proliferative processes in the vitreous cavity. Recombinant prourokinase (Gemaza, LLC NPP TECHNOGEN, patent No. 2216348) can be used as an active substance that promotes lysis of the subretinal blood clot. "Hemase" is a lyophilized enzyme preparation containing recombinant prourokinase and catalyzing the conversion of plasminogen to plasmin-serine protease, by it can lyse fibrin clots, and has a high specificity of action, since it activates plasmitogen mainly in the area of the clot, which reduces the risk of possible bleeding and hemorrhage.

The technical problem is the difficult accessibility of drug delivery to the source of hemorrhage, which is located under the retina and is limited by it, it is necessary to create an effective method of treating subretinal hemorrhages with minimal trauma and with a low risk of postoperative complications,

The technical result to which the claimed invention is directed is to improve the functional results of surgical intervention, minimize trauma, reduce the risk of postoperative complications, reduce the risk of retinal detachment, due to translocation of blood from the central zone and dissolve it in direct contact with the drug substance.

The technical result is achieved by the fact that in a method for the surgical treatment of subretinal hemorrhages, including subtotal vitrectomy with removal of the posterior hyaloid membrane, the introduction of a solution of recombinant prourokinase, it is new that the solution of recombinant prourokinase is injected into the subretinal space (under the retina), for which the retinal fibers are stratified the above solution, while previously in the area of delamination locally remove the inner boundary membrane.

A recombinant prourokinase solution is administered along with air bubbles.

The retina is stratified with a stream of recombinant prourokinase solution using a 41G cannula, connected using a Luer to Luer adapter with a silicone tube to a 1.0 ml syringe, while 0.2 ml of sterile air is collected through a filter to a recombinant prourokinase solution.

A solution of recombinant prourokinase is administered in an amount of 0.5-0.7 ml of 1500-2000 IU.

Due to the tension of surface membranes on air bubbles, there is an increase in the movement of red blood cells, the movement of cellular elements along the walls of the bubbles, due to which diffusion and resorption processes are activated.

Due to the local removal of the inner border membrane (200 μm), without retinotomy, as well as due to the delamination of the retinal fibers and the introduction of a recombinant prourokinase solution at low perfusion pressure, the injection site remains airtight and there are no conditions for the development of regmatogenous retinal detachment.

Figure 1 presents a photograph of the adapter from "Luer" to "Luer" with a silicone tube.

In FIG. 2 is a photograph of a 41G cannula.

In FIG. Figure 3 shows a photograph of a device for subretinal administration of solutions (41G cannula connected using an adapter from Luer to Luer with a silicone tube to a 1.0 ml syringe).

In FIG. 4 shows optical coherence tomography (OCT) of patient 1 before surgery.

In FIG. 5 shows the OST of patient 1 1 month after surgery.

In FIG. 6 shows the OST of patient 1 6 months after surgery.

In FIG. 7 is a photograph of the fundus of patient 1 6 months after surgery.

In FIG. 8 shows the OST of patient 2 before surgery.

In FIG. 9 is a photograph of the fundus of patient 2 before surgery.

In FIG. 10 shows the OST of patient 2 5 days after surgery.

In FIG. 11 shows the OST of patient 2 1 month after surgery.

In FIG. 12 is a photograph of the fundus of patient 3 before surgery.

In FIG. 13 is a photograph of the fundus of patient 3 1 month after surgery.

In FIG. 14 shows the OST of patient 3 1 month after surgery.

In FIG. 15 is a photograph of the fundus of patient 3 3 months after surgery.

In FIG. 16 presents the OST of patient 3 3 months after surgery.

The operation is carried out as follows.

1. Microinvasive three-port subtotal vitrectomy 25G + 27G. Three sclerectomy punctures are made 4 mm from the limbus and ports are installed. Frequency from 3000 to 5000 cuts per minute, vacuum from 5 to 400 mm RT. To detail the structure of the posterior cortical layers of the vitreous, triamcenolone staining is used.

2. Removal of the posterior hyaloid membrane (DGM) is carried out using an aspiration technique, starting from the optic nerve disk (optic nerve disc), gradually lifting it to the periphery using a vitreotome.

3. Staining of the inner border membrane (VPM) with Brilliant Peel solution (Brilliant blue), followed by removal of the VPM locally, in the area of delamination with tweezers.

4. Separation of the retina with a stream of a recombinant prourokinase solution using a 41G cannula connected with a 1.0ml syringe to the Luer to Luer silicone tube to a 1.0 ml syringe, while 0.2 ml of sterile air is drawn into the recombinant prourokinase solution through a filter and the introduction of a solution of recombinant prourokinase into the subretinal space.

5. The operation ends with the removal of ports, without gas-air tamponade.

The technology of subretinal administration of a solution of recombinant prourokinase (or drug solutions) during microinvasive vitrectomy with subretinal hemorrhages (with hemorrhagic age-related macular degeneration (AMD), hypertension, injuries) using a 41G cannula (Fig. 2) connected using a silicone tube. 1) (adapter) to a 1.0 ml syringe (Fig. 3), while 0.2 ml of sterile air is collected through a filter to a solution of recombinant prourokinase.

By delaminating the retinal fibers (tissue) with a fluid (solution) stream, a recombinant prourokinase solution along with air bubbles is introduced into the subretinal space (under the retina) to flush out the spilled blood (or impact on the spilled blood). The introduction is carried out without conducting a retinotomy opening, which avoids the development of retinal detachment, and also avoids the restrictive laser coagulation of the retinotomy site (extra burn). The separated retinal tissue spontaneously closes and does not require additional exposure: laser retinal coagulation (LKS) or gas-air tamponade. In this case, a minimal effect on the retina is made, the residual liquid + recombinant prourokinase solution dissolves the blood. The operation ends without gas-air tamponade, on the water.

Patient 1

Before the operation of 10.28.17 g Visus OS = 0.05 n / a.

Diagnosis: Subretinal hemorrhage (Fig. 4).

10.28.17, Surgical treatment: posterior vitrectomy (CVE) + subretinal administration of a recombinant prourokinase solution.

After 1 month, Visus OS = 0.3 n / a (Fig. 5).

After 6 months, Visus OS = 0.5 n / a (Fig. 6, 7).

Patient 2

Before Visus surgery, OD = 0.05 n / a.

Diagnosis: AMD (hemorrhagic form). Subretinal hemorrhage (Fig. 8, 9).

09/12/18, Surgical treatment: CVE + subretinal administration of a solution of recombinant prourokinase.

After 5 days, Visus OD = 0.3 n / a (Fig. 10).

After 1 month, Visus OD = 0.3 n / a (Fig. 11).

Patient 3

Before Visus surgery, OD = 0.01 n / k.

Diagnosis: Subretinal hemorrhage (Fig. 12).

07/26/18, Surgical treatment: CVE + subretinal administration of a solution of recombinant prourokinase.

After 1 month MKOZ OD = 0.8 n / a (Fig. 13, 14).

After 3 months MKOZ OD = 1,0 (Fig. 15, 16).

Thus, the proposed method allows you to reliably, with minimal impact on the retina and, therefore, with minimal trauma to remove blood from the Central zone of the retina, which reduces the risk of postoperative complications.

Claims (3)

1. A method for the surgical treatment of subretinal hemorrhages, including subtotal vitrectomy with removal of the posterior hyaloid membrane, the introduction of a recombinant prourokinase solution, characterized in that the recombinant prourokinase solution is introduced into the subretinal space under the retina, for which the retinal fibers are stratified by a stream of the above solution, previously bundles locally remove the inner boundary membrane. 2. The method according to p. 1, characterized in that the solution of recombinant prourokinase is administered together with air bubbles. 3. The method according to p. 1 or 2, characterized in that the retina is stratified by a stream of a recombinant prourokinase solution using a 41G cannula, connected using a Luer to Luer adapter with a silicone tube to a 1.0 ml syringe, 0.2 ml of sterile air is collected through a filter using a recombinant prourokinase solution.

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