Viscoelastic compound for stabilizing inner membrane flap in macular pore surgery

Abstract

The invention discloses a viscoelastic compound for stabilizing an inner bound flap in a macular pore surgery, the viscoelastic compound comprises a viscoelastic agent and a penetrant, the viscoelastic agent is any one or a compound of more than two of hyaluronic acid, hydroxypropyl methyl cellulose, methyl cellulose and cross-linked HA; the penetrant is a solution of glucose, cane sugar, mannitol or sorbitol with the mass concentration of 5-20%. According to the application, the specific viscoelastic agent and the penetrant are uniformly fused to form the viscoelastic compound, the viscoelastic compound is accurately coated on a macular pore area in a minimally invasive vitreous surgery to cover the whole pore area, and the viscoelastic compound can provide immediate mechanical fixation, so that the turnover ILM flap is stable and does not move in the operation process, and the operation efficiency is improved. The dissection closing rate of the complex macular hole and postoperative visual function recovery are improved.

Description

Technical Field

[0001] This application belongs to the field of medical device technology, specifically relating to a viscoelastic complex for stabilizing the internal limiting flap during macular hole surgery. Background Technology

[0002] Macular holes (MH) are defects in the entire or partial layer of the neuroepithelial layer in the fovea region of the retina, leading to severe central vision loss, central scotoma, and distorted vision. For persistent or large macular holes, surgical intervention is the primary treatment. Following standard pars plana vitrectomy, dissection of the internal limiting membrane (ILM) has become a crucial step, aiming to relieve tangential traction on the retina and promote hole closure. However, in complex cases such as large-diameter (typically ≥400-500µm), chronically present, or complicated by high myopia (significantly elongated long axis, traction on the eyeball, and weakened retinal tissue), simple complete ILM dissection does not guarantee a high success rate in anatomical closure and functional recovery.

[0003] To improve the closure rate of complex eye tears, the inverted ILM flap technique is widely used. This technique involves inverting the dissected ILM flap and covering or filling the eye tear surface, acting as a biological scaffold to support the migration and proliferation of neuroepithelial cells, thereby promoting tear closure. However, this technique presents significant challenges during operation: the ILM flap itself is not thin, is soft, and elastic, making it prone to curling and drifting in the vitreous cavity fluid environment, or accidental aspiration and displacement due to intraocular fluid flow (such as irrigation fluid or aspiration) during surgery. This makes it difficult for the surgeon to accurately and stably place the flap and adhere it to the eye tear area, affecting the reliability and repeatability of the technique.

[0004] To stabilize ILM flaps during surgery, the most common methods currently used are viscoelastic agents or heavy-density substances. For example, heavy-density liquids such as perfluorocarbon liquids (PFO) are used; PFO's high density can "press" the flap against the retinal tear. However, it carries a clear risk of retinal toxicity and must be completely removed before the end of surgery; it cannot remain for long periods. Improper handling may lead to residues, and PFO itself lacks viscoelasticity, limiting its effectiveness in flap adhesion and fixation. Another method is to use viscoelastic agents for short-term coverage, such as injecting sodium hyaluronate onto the flap surface for temporary coverage. However, conventional viscoelastic agents are easily diffused and diluted in intraocular fluids, exhibiting poor stability and short duration, making it difficult to provide continuous and reliable stability throughout the critical procedure. Further optimization using a mixture of sodium hyaluronate and saline buffer, while extending its duration, significantly dilutes its viscoelasticity and cohesion, resulting in insufficient mechanical support, weak settling and spatial retention capabilities, and inability to effectively resist fluid flow disturbances, leaving the flap prone to displacement.

[0005] In summary, existing substances or methods for stabilizing ILM flaps have limitations to varying degrees in terms of biocompatibility, intraoperative stability, ease of operation, and postoperative safety. Summary of the Invention

[0006] In view of this, the primary objective of this application is to provide a viscoelastic complex for stabilizing the internal limiting membrane flap in macular hole surgery. A specific viscoelastic agent and a penetrant are uniformly fused to form a viscoelastic complex with suitable viscoelasticity and specific gravity, thereby achieving precise coating in minimally invasive vitrectomy. This viscoelastic complex can provide immediate mechanical fixation, ensuring the stability of the flipped ILM flap during the operation, improving the anatomical closure rate of complex macular holes and postoperative visual function recovery.

[0007] To achieve the above objectives, this application adopts the following technical solution: One aspect of this application discloses a viscoelastic complex for stabilizing the internal limiting flap during macular hole surgery, comprising a viscoelastic agent and a penetrant, wherein the viscoelastic agent is any one or a combination of two or more of hyaluronic acid, hydroxypropyl methylcellulose, methylcellulose, and cross-linked HA; and the penetrant is a solution of glucose, sucrose, mannitol, or sorbitol with a mass concentration of 5%-20%.

[0008] Another aspect of this application discloses a medicine box comprising a viscoelastic agent and a penetrant as defined in this application.

[0009] The beneficial effects of this application are: This application discloses a viscoelastic complex formed from a specific viscoelastic agent and a penetrant. When applied to the internal limiting membrane (ILM) flap inversion surgery, it provides immediate mechanical fixation and settling support for the inverted ILM flap during the procedure, significantly improving flap stability and flap closure rate. Compared to traditional ILM inversion surgery, where flaps are prone to curling, drifting, or aspiration in large-diameter, chronic, or highly myopic macular holes, requiring PFO or other auxiliary instruments for fixation, and involving complex procedures and potential risks, the viscoelastic complex of this application achieves stable fixation without additional instruments, offering significant advantages in surgical procedures. Attached Figure Description

[0010] Figure 1 This is a schematic diagram illustrating the operation of mixing a viscoelastic agent and a penetrant to form a viscoelastic complex in a preferred embodiment of this application.

[0011] Figure 2 This is a diagram illustrating the procedures performed on the patient during surgery.

[0012] Figure 3 OCT imaging of 14 patients before and after surgery. Detailed Implementation

[0013] The embodiments of this application will be clearly and completely described below. The technical solutions in the embodiments described below are exemplary and only possible technical implementations of this application, not all possible implementations. Those skilled in the art can combine the embodiments of this application to obtain other embodiments without creative effort, and these embodiments are also within the protection scope of this application.

[0014] This application discloses a viscoelastic complex for stabilizing the internal limiting flap in macular hole surgery, comprising a viscoelastic agent and a penetrant. The viscoelastic agent is any one or a combination of two or more of hyaluronic acid, hydroxypropyl methylcellulose, methylcellulose, and cross-linked HA. The penetrant is a solution of glucose, sucrose, mannitol, or sorbitol with a mass concentration of 5%-20%.

[0015] As a preferred example, the volume ratio of the viscoelastic agent to the penetrant is 1:2 to 2:1.

[0016] In some specific examples, hyaluronic acid is used as the viscoelastic agent and glucose solution as the penetrant. The viscoelastic agent has a mass concentration of 1%-2%, for example, any concentration or a range between 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, and 2.0%. The glucose solution has a mass concentration of 5%-20%, for example, any concentration or a range between 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, and 20%.

[0017] It is understood that this application can meet the individualized needs of different patients by adjusting the molecular weight of the viscoelastic agent, the mass concentration of the viscoelastic agent and the penetrant, and the ratio of the viscoelastic agent and the penetrant. Specifically, it optimizes the viscoelasticity and sedimentation effect according to the size, duration, and long axis of the eyeball. For small macular holes (<400μm): a medium concentration of HA (approximately 1-1.5% by mass) is usually selected, with a mixing volume ratio (HA: 10% glucose) of 1:1 or 1:2, to ensure adequate viscoelasticity and local retention time, while facilitating intraoperative manipulation and removal. For large or complex macular holes (≥400-600μm) and high myopia: a high concentration of HA (approximately 1.5-2% by mass) can be selected, with a mixing volume ratio (HA: 10% glucose) of 1:1, to provide stronger support and longer local retention time, while paying attention to achieving a balance between "stability" and "removability". Those skilled in the art can determine the specific concentration and ratio range through experimental methods, and therefore there are no particular limitations.

[0018] Furthermore, the molecular weight of hyaluronic acid can also be appropriately selected according to the condition of macular holes, such as size and chronicity, to adjust the viscoelasticity and sedimentation properties of the viscoelastic complex. Specifically, this includes, but is not limited to, hyaluronic acid with medium molecular weight (0.5-1.0 MDa), high molecular weight (1.0-2.0 MDa), or ultra-high molecular weight (>2.0 MDa). As a preferred example, the molecular weight of the hyaluronic acid is 1.0-2.0 MDa.

[0019] Another aspect of this application discloses a kit comprising a viscoelastic agent and a penetrant as defined in the first aspect of this application. In this kit, the viscoelastic agent and penetrant are appropriately pre-packaged for direct use during subsequent surgical procedures.

[0020] Understandably, in addition to the necessary viscoelastic and penetrant, the medicine box usually also contains corresponding consumables and instructions for use, which should specify the usage method.

[0021] In some specific examples of this application, the methods of using viscoelastic agents and penetrants include two types, either of methods (1)-(2): Method (1): After sterilizing the viscoelastic agent and penetrant, mix them thoroughly to form a viscoelastic composite liquid with uniform liquid and suitable fluidity. Apply the viscoelastic composite liquid to the crack area in one application or at multiple points to cover the entire crack area. Method (2): After sterilizing the viscoelastic agent and the penetrant, the viscoelastic agent is first coated on the crack area to form a basic viscoelastic layer, and then the penetrant is locally added to cover the crack area.

[0022] The sterilization can be achieved through filtration using a 0.22μm filter membrane.

[0023] In method (1), the viscoelastic composite liquid can be mixed in a manner well known in the art. For example, in some specific examples, the viscoelastic agent and the penetrant are injected separately into a stopcock tee via a syringe for mixing, and the viscoelastic composite liquid is uniformly mixed by repeatedly pushing and pulling the syringe. In other specific examples, the viscoelastic agent and the penetrant can be mixed thoroughly and uniformly by micro-magnetic stirring.

[0024] The present application will be further illustrated below with reference to specific embodiments. It should be noted that the specific embodiments below are for illustrative purposes only and do not limit the scope of the present application in any way.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein in the specification of this application is for the purpose of describing particular embodiments only and is not intended to be limiting of this application.

[0026] In addition, unless otherwise specified, methods without detailed conditions or steps are conventional methods, and the reagents and materials used are commercially available.

[0027] Table 1. Composition of viscoelastic composites in each embodiment

[0028] In practical use, follow the proportions in Table 1 and use the three-way cock system ( Figure 1To mix the viscoelastic composite solution, specifically, the viscoelastic agent and penetrant are injected into two separate 1ml syringes, which are then connected by a sterile three-way stopcock to form a closed mixing system. With all channels of the stopcock fully open, the operator alternately presses the pistons of the two syringes, causing the two solutions to circulate back and forth through the stopcock. This reciprocating cycle is typically repeated 20 to 30 times until the mixture achieves a uniform viscosity, color, and flow characteristics.

[0029] Effect verification The application of the viscoelastic complex from Example 1 in 14 patients with macular holes is demonstrated. All patients underwent vitrectomy using an inverted ILM flap technique. The viscoelastic complex formed in Example 1 was applied topically at multiple points on the inverted ILM flap to enhance flap stability. Specific procedures are described in [link to procedure]. Figure 2 Under posterior anesthesia, a standard three-port total vitrectomy (PPV) was performed using a Leica 23G or 25G sutureless vitrectomy system with contact lens assistance. After completing the core and peripheral vitrectomy, the posterior vitreous was gently lifted and completely removed to eliminate residual retinal traction. Subsequently, the internal limiting membrane (ILM) was stained with indocyanine green (ICG, 5 mg / mL) and immediately rinsed to reduce dye exposure. The ILM was dissected from the edge of the macular hole (MH), retaining the remnant attached to the temporal edge, and trimmed into a rectangular flap for the inverted ILM flap technique. The temporal ILM flap was carefully inverted to cover the macular area, ensuring full contact between the flap and the edge of the hole. Subsequently, a diluted sodium hyaluronate solution mixed with a 10% glucose solution is gently applied to the macular region (the surface of the macular hole and the flap being rotated), forming a stable "viscoelastic pool," a viscoelastic layer 0.1-0.3 mm thick. This provides a near-static environment for flap manipulation. Specifically, this viscoelastic layer, relying on its viscoelastic properties and specific gravity, can temporarily fix the flap during surgery, reducing the occurrence of curling, drift, and aspiration. For patients with retinal detachment, subretinal fluid is drained through the macular hole using a reverse irrigation needle to reduce retinal elevation and flatten the macular region. Subsequently, fluid and air exchange is carefully performed through the optic disc surface to avoid interfering with the viscoelastic pool or internal limiting membrane flap. After surgery, 18% C3F8 gas is injected into the vitreous cavity, and the patient is instructed to maintain a face-down position for at least one week to promote macular hole closure.

[0030] Outcome parameters included postoperative best-corrected visual acuity (BCVA), macular hole closure rate, retinal reattachment rate, and surgical complications. Patient demographics and ocular characteristics, including age, axial length, macular hole diameter, and follow-up time, were recorded. Results are as follows... Figure 3 As shown in Table 2: Table 2. Pre- and post-operative data of 14 patients.

[0031] The mean axial length of the 14 patients with complex macular holes was (25.08±2.73) mm (21.83~29.65 mm), and the mean macular hole diameter was (474.23±239.16) µm (149~980 µm). The viscoelastic complex described in this application was used to stabilize the internal limiting flap. The follow-up period was 8~45 days (mean 16.92±11.59 days).

[0032] The best-corrected visual acuity (BCVA) after stabilizing the internal limiting membrane flap using the viscoelastic complex described in this application improved by approximately 38.46% compared to preoperative values. Macular holes were successfully closed in all patients, with a 100% retinal reattachment rate in the two patients with preoperative retinal detachment. No complications were observed during follow-up. OCT (optical coherence tomography) imaging showed that the inverted ILM flap was stably attached to the retinal hole after being covered with a viscoelastic composite fluid during surgery. The fluid layer maintained the flap position during fluid-gas replacement and gas filling (SF6 or C3F8), avoiding the curling or displacement problems common in traditional methods.

[0033] The above results indicate that using the viscoelastic complex described in this application for stabilizing the internal limiting membrane flap can provide a safe, effective, and controllable treatment option for complex macular holes. This viscoelastic complex can simultaneously provide mechanical fixation, sedimentation support, and local microenvironment optimization, significantly enhancing flap stability and improving intraoperative controllability. It not only ensures a high closure rate but also promotes postoperative visual function improvement. Furthermore, it does not require additional instruments or complex procedures, providing a feasible surgical strategy for patients with large macular holes, chronic macular holes, or axial elongation, demonstrating promising clinical application prospects.

[0034] It should be noted that this application is not limited to the above-described embodiments. The above embodiments are merely examples, and any embodiments with the same structure and effect as the technical concept within the scope of this application are included in the technical scope of this application. Furthermore, various modifications that can be conceived by those skilled in the art to the embodiments, and other ways of constructing by combining some of the constituent elements of the embodiments, without departing from the spirit of this application, are also included in the scope of this application.

Claims

1. A viscoelastic complex for stabilizing the internal limiting flap during macular hole surgery, characterized in that, It includes a viscoelastic agent and a penetrant. The viscoelastic agent is any one or a combination of two or more of hyaluronic acid, hydroxypropyl methylcellulose, methylcellulose, and cross-linked HA. The penetrant is a solution of glucose, sucrose, mannitol, or sorbitol with a mass concentration of 5%-20%.

2. The viscoelastic composite as claimed in claim 1, characterized in that, The volume ratio of the viscoelastic agent to the penetrant is 1:2 to 2:

1.

3. The viscoelastic composite as described in claim 1, characterized in that, In the viscoelastic composite, the penetrant is a glucose solution with a mass concentration of 10%.

4. The viscoelastic composite as claimed in claim 1, characterized in that, The viscoelastic agent is hyaluronic acid.

5. The viscoelastic composite as claimed in claim 1, characterized in that, The viscoelastic agent has a molecular weight of 1.0-2.0 MDa.

6. A medicine box, characterized in that, The medicine box includes a viscoelastic agent and a penetrant as defined in any one of claims 1-5.

7. The medicine box as described in claim 6, characterized in that, The medicine box also includes an instruction manual, which specifies how to use the medicine.

8. The medicine box as described in claim 7, characterized in that, The method of use is any one of methods (1)-(2): Method (1): After sterilizing the viscoelastic agent and the penetrant, they are thoroughly mixed to form a viscoelastic composite liquid. The viscoelastic composite liquid is applied once or locally at multiple points to the tear area and the surface of the flipped skin flap to cover the tear area. Method (2): After sterilizing the viscoelastic agent and the penetrant, the viscoelastic agent is first applied to the tear area and the surface of the flap to form a basic viscoelastic layer, and then the penetrant is locally added to cover the tear area.

9. The medicine box as described in claim 8, characterized in that, The sterilization is achieved by filtration through a 0.22μm filter membrane.

10. The medicine box as described in claim 8, characterized in that, In method (1), the viscoelastic agent and the penetrant can be injected into the three-way tube by two separate syringes, and mixed by repeated pushing and pulling of the syringes.

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