RU2841286C1 - Method of surgical treatment of primary through macular retinal rupture - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, specifically to ophthalmology, and can be used for surgical treatment of primary through macular rupture (MR), retina. Upper inverted single-layer fragment of the internal limiting membrane (ILM) is formed. Formed upper inverting one-layer ILM fragment is turned over and placed with its inner side on the MR. ILM is not removed on the other retinal segments. Then fluid is replaced with air. ILM fragment straightening is achieved in air environment. Surface of a dried inverted ILM fragment is coated with 2 drops of autologous lean blood plasma (PPP). Plasma is exposed for 1 minute, then a retinal surface is slightly dried with removing PPP and residual intraocular fluid. Further, the surface of the ILM fragment is coated with 5 drops of PPP. Exposure is maintained for 5 minutes. Then air is replaced with BSS.

EFFECT: invention reduces the number of intraoperative manipulations, performs tamponade-free surgery while maintaining the stable position of the ILM fragment, reliable blocking of the macular hole with an ILM fragment, MR closure with recovery of the normal histological retinal architecture in the fovea, high functional therapeutic effect, minimized risk of intra- and postoperative complications.

1 cl, 1 ex

Description

The invention relates to medicine, namely to ophthalmology, and can be used for surgical treatment of primary through-and-through macular hole (MP) of the retina using an upper inverted fragment of the internal limiting membrane (ILM) and platelet-depleted autologous blood plasma.

For a long time, the generally accepted method of treating MP was vitrectomy with removal of the ILM and subsequent tamponade of the vitreous cavity [Eckardt C., Eckardt U., Groos S. et al. Removal of the internal limiting membrane in macular holes. Clinical and morphological findings // Ophthalmologe. - 1997. - Vol. 94. - P. 545-551].

To date, the attitude towards the removal of the ILM is ambiguous, more and more authors talk about the traumatic effect of this procedure on the retinal structures, which leads to low functional results, despite the achieved anatomical success [Lyskin P.V., Volodin P.L., Makarenko I.R. Functional results of surgical treatment of macular holes with complete preservation of the internal limiting membrane in comparison with the traditional technique. Russian Ophthalmological Journal. 2023; 16(4):44-49. Casini G., Mura M., Figus M., Loiudice P., Peiretti E., De Cilia S., Fuentes T., Nasini F. Inverted internal limiting membrane flap technique for macular holesurgery without extra manipulation of the flap // Retina. - 2017. - Vol. 37. - No 11. - P. 2138-2144].

There are also publications on the advisability of abandoning tamponade of the vitreous cavity with any tamponade agents in order to minimize the risk of damage to the retinal neuroreceptor apparatus [Djatikusumo A., Victor A.A., Yudantha A.R. et al. Risk factors of post-operative optic nerve injury after vitrectomy: a systematic review. F1000Research2023, 12:1587].

In addition, in recent years, various types of autologous blood plasma have been used in the treatment of MP, which help to reduce the trauma of surgical intervention [Naresh B.; Piyush K.; et all Comparison of platelet-rich plasma and inverted internal limiting membrane flap for the management of large macular holes. A pilot study. Indian Journal of Ophthalmology. 2020; 68(5):880-884. Krupina E.A. Analysis of molecular and biological aspects of the use of PRP and ACP therapy. Bulletin of the National Medical and Surgical Center named after N.I. Pirogov. 2020; 15(3, part 2):80-85].

The above makes it relevant to develop new effective and safe methods of surgical treatment of penetrating retinal MPs with minimization of the area of ILM peeling, increased reliability of fixation of the inverted ILM fragment to the retina in the MP zone, and the absence of prolonged postoperative tamponade of the vitreous cavity.

A method of surgical treatment of retinal MP is known (RU patent for invention No. 2773204), according to which after three-port vitrectomy, circular maculorexis, application of platelet-rich autologous plasma (PRP) in the "air" medium and formation of a fibrin film, a drop of PFOS is applied to the macular area. Then the vitreous cavity is filled with BSS, after 5 minutes the PFOS is aspirated in the "BSS" medium without subsequent tamponade of the vitreous cavity. However, in the "BSS" medium there are difficulties with removing PFOS bubbles, which requires additional manipulations, increasing the risk of retinal injury and involuntary detachment of the fibrin film from the retinal surface, which can lead to unblocking and non-closure of MP.

A method of surgical treatment of primary penetrating MP of any diameter is known (RU patent for invention No. 2784894), according to which an invertible single-layer fragment of the ILM is formed, which is turned over and placed with the inner side on the MP, thereby blocking it, 2-3 drops of platelet-rich blood plasma (PRP) are applied to the surface of the invertible fragment of the ILM, PFOS is introduced into the area of the macular hole for 5-7 minutes, then PFOS is removed, air is replaced with BSS without subsequent tamponade of the vitreous cavity.

The disadvantage of this method is a large number of intraoperative manipulations, as well as the need to use PFOS. In the air environment, as in the BSS environment, there are difficulties with removing PFOS bubbles entangled in the layers of the PRP fibrin film, which has a complex three-dimensional structure. This requires additional manipulations, increasing the risk of injury to the retina and involuntary detachment of the fibrin film from the retinal surface, which can lead to unblocking and non-closure of the MP. Another significant disadvantage of this technique is the rapid contraction of platelet-rich plasma, which leads to compression of the clot fixed on the retinal surface to a degree directly proportional to the number of platelets in the plasma. It is known that with an increase in the concentration of platelets in the amount of more than 500 thousand/μl, the degree of contraction increases by more than 30% within 20 minutes [Tutwiler V, Litvinov RI, Lozhkin AP, Peshkova AD, Lebedeva T, Ataullakhanov FI, Spiller KL, Cines DB, Weisel JW. Kinetics and mechanics of clot contraction are governed by the molecular and cellular composition of the blood. Blood. 2016; 127(1): 149-59]. This, in turn, given the absence of tamponade, can cause deformation or detachment of the ILM fragment from the retinal surface in the early postoperative period. Also, in the work of foreign authors it was shown that the proliferation of fibroblasts and the production of type 1 collagen significantly increase as the concentration of platelets increases. This may lead to increased fibroblast proliferation on the retinal surface in the late postoperative period and cause relapse of epiretinal fibrosis [Lui Y, Kalen A, Risto O, et al: Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent. Wound Repair Regen 10:336, 2002].

The author was unable to find in the available sources a method for surgical treatment of primary penetrating MP using the upper inverted fragment of the ILM and platelet-depleted autologous blood plasma.

The objective of the invention is to develop a new effective low-traumatic method of surgical treatment of primary penetrating MP using an upper inverted fragment of the ILM and platelet-depleted autologous blood plasma.

The technical result of the claimed method is a reduction in the number of intraoperative manipulations, performing tamponade-free surgery while maintaining a stable position of the ILM fragment, reliable blocking of the macular hole with the ILM fragment, closure of the MP with restoration of the normal histological architecture of the retina in the fovea, high functional treatment results, minimization of the risk of intra- and postoperative complications.

The technical result is achieved in that, according to the invention, an upper invertible single-layer fragment of the ILM is formed, which is turned over and placed on the MP with the inner side, while the ILM is not removed from other areas of the retina; then the liquid is replaced with air, in the air medium the ILM fragment is straightened on the surface of the retina, after which 2 drops of autologous platelet-poor plasma (PPP) are applied to the surface of the ILM fragment, which is a fraction of blood plasma containing 5×10 ⁹ platelets/ml or less [Zhang J, Zhang J, Zhang N, Li T, Zhou X, Jia J, Liang Y, Sun X, Chen H. The Effects of Platelet-Rich and Platelet-Poor Plasma on Biological Characteristics of BM-MSCs In Vitro. Anal Cell Pathol (Amst). 2020 Aug 26; 2020:8546231. doi: 10.1155/2020/8546231], then PPP is exposed for 1 minute, then the retinal surface is dried with the removal of PPP and residual intraocular fluid, while due to the polymerization of PPP, the final straightening and fixation of the edges of the ILM fragment to the retina occurs, then 5 drops of PPP are applied to the surface of the fragment, exposure is carried out for 5 minutes, then air is replaced with liquid. PFOS solution is not used at any stage of the surgery. The technical result is achieved due to the fact that:

1) formation of an inverted fragment of the ILM in the upper part of the macular region, without circular peeling of the ILM concentrically to the MP, reduces trauma to the inner layers of the retina, reduces the risk of damage to the structure of the macular zone, dissociation of nerve fibers in the late postoperative period;

2) RRR is used as a bioglue that fixes the ILM fragment on the retinal surface in the desired position without the intraoperative use of PFOC. RRR also creates an additional protective layer that prevents the reverse rotation of the ILM fragment and the ingress of fluid into the MP zone in the early postoperative period;

3) unlike the commonly used PRP (platelet-rich plasma), PPP does not contain sodium citrate, the safety profile of which for human retinal structures has not been studied; it also contains virtually no leukocytes, which reduces the risk of postoperative inflammation;

4) the amount of platelets in the PPP (5*10 ⁹ ), reduced by 30-100 times compared to blood plasma (150-400*10 ⁹ ), ensures slow, prolonged and moderate contraction of the clot, which ensures long-term reliable fixation of the inverted fragment of the ILM to the retina and blocking of the MP, the absence of the risk of unblocking the MP due to rapid contraction of the fibrin clot and, as a consequence, the absence of the risk of displacement, deformation of the ILM fragment or detachment of the fibrin clot from the surface of the retina in the early postoperative period;

5) when first applied to the surface of the ILM fragment, slow uniform polymerization of PPP (2 drops) in the absence of excess platelets ensures fixation of the ILM fragment in a position blocking the macular hole. This technique avoids the need for long-term drying of the ILM fragment and the surrounding retina, and reduces the risk of its trauma;

6) exposure to PPP for 1 minute is necessary to initiate fibrin polymerization;

7) the absence of the stage of using PFOS eliminates the risks of complications associated with manipulations to remove it from the eye, as well as the risk of leaving PFOS in the vitreous cavity, which causes visual discomfort from “floating balls” and a toxic effect on intraocular structures;

8) repeated application of 5 drops of PPP to the surface of the ILM fragment allows the creation of a fibrin film of sufficient thickness for reliable prolonged fixation of the fragment without the use of tamponade of the vitreous cavity with vitreous substitutes;

9) 5-minute exposure upon repeated application of PPP to the surface of the VLM fragment is necessary for the polymerization of fibrin molecules, aggregation of polymerized molecules, and the beginning of the formation of a three-dimensional fibrin-polymer network.

The method is carried out as follows.

Before the operation, 6 ml of venous blood is collected from the patient to obtain autologous platelet-poor plasma (PPP). The blood is collected in a sterile disposable plastic tube with a lid. The blood is then centrifuged for 15 minutes at 1600g. After that, 0.1 ml of the upper layer of PPP plasma is collected from the tube. The procedure for obtaining PPP is performed directly in the operating room, in parallel with the surgical intervention, in such a way as to minimize the time from the moment of obtaining PPP to the moment of its intravitreal use.

During the surgical intervention, a transconjunctival 3-port 27G subtotal vitrectomy is performed. The posterior cortical layers of the vitreous body are separated from the center of the retina to the periphery using the aspiration method. An upper inverted single-layer fragment of the ILM is formed to close the macular hole. The formed upper inverted single-layer fragment of the ILM is turned over and placed with the inner side on the MP, thereby blocking it. The remaining areas of the retina, including in the projection of the papillomacular bundle, are left intact, that is, the ILM is not removed from them. Next, the fluid is replaced with air; in the air medium, the ILM fragment is straightened on the retinal surface. After this, 2 drops of PPP are applied to the surface of the dried inverted fragment of the ILM. Plasma is exposed for 1 minute, then the retinal surface is dried with the removal of PPP and residual intraocular fluid. Due to the polymerization of PPP, the final straightening and fixation of the edges of the ILM fragment to the retina occurs, which eliminates its displacement or folding. Next, 5 drops of PPP are applied to the surface of the ILM fragment. The exposure is maintained for 5 minutes. Then the air is replaced with BSS, while the vitreous cavity is filled with BSS gradually using a 20 ml syringe and a straight 27G flute-type cannula, under direct visual control, applying BSS drops directly to the macular zone of the retina, which prevents the occurrence of swirls of fluid in the vitreous cavity and separation of the fibrin film from the retina. The operation is completed without tamponade of the vitreous cavity.

The invention is illustrated by the following clinical data.

Clinical example.

Patient O. Diagnosis: OD - primary through macular retinal hole of medium diameter. Complaints of distortion of lines and objects, low vision OD. Best corrected visual acuity (BCVA) OD 0.3. According to microperimetry, central light sensitivity (6 degrees from the fixation point) (CLS) is 26.5 dB. According to spectral optical coherence tomography (SOCT), the minimum diameter of the macular hole is 334 μm.

Surgical treatment was performed using the claimed method with the formation of an upper inverted fragment of the ILM, using autologous platelet-poor blood plasma (PPP), without tamponade of the vitreous cavity.

During the surgical intervention, an upper inverted single-layer fragment of the ILM was formed, which was turned over and placed on the MP with the inner side, while the ILM was not removed from other areas of the retina; then the liquid was replaced with air, in the air medium, the ILM fragment was straightened on the surface of the retina, after which 2 drops of autologous platelet-poor plasma (PPP) were applied to the surface of the ILM fragment, the PPP exposure was maintained for 1 minute, then the retinal surface was dried with the removal of PPP and residual intraocular fluid, while due to the polymerization of PPP, the final straightening and fixation of the edges of the ILM fragment to the retina occurred, then 5 drops of PPP were applied to the surface of the fragment, the exposure was carried out for 5 minutes, then the air was replaced with liquid. PFOS solution was not used at any stage of the surgery. The operation was completed without tamponade of the vitreous cavity. No intraoperative complications arose.

Positive dynamics were observed the day after the operation. According to the SOCT data: the macular hole was blocked by a fragment of the ILM, the minimum diameter of the through retinal defect decreased to 270 μm. A hyperreflective film (HRF) with a thickness of 350 μm was visualized on the surface of the retina.

Seven days after the surgery, according to the SOCT data: the edges of the MP are adapted with preservation of the defect at the level of the outer segments of the photoreceptors and the ellipsoid with local detachment of the neuroepithelium in the projection of the fovea (up to 106 μm in height, up to 428 μm in diameter). The MP is blocked by an inverted fragment of the ILM with the formation of a duplication. In the upper segment of the macular region, there are defects of the inner surface of the retina as a result of ILM peeling. The fibrin film of the RRR was not visualized, the small cystic edema along the edge of the rupture was resorbed. BCVA was 0.3. According to microperimetry, the central HF increased to 27.4 dB. The patient subjectively noted improved vision and reduced distortions.

One month after the operation, according to the SOCT data: the edges of the MP are adapted with preservation of the defect at the level of the outer segments of the photoreceptors and the ellipsoid and local detachment of the neuroepithelium in the projection of the fovea (H up to 103 μm, diameter up to 420 μm). The MP is blocked by an inverted fragment of the ILM. BCVA is 0.4. According to microperimetry data, the central HF increased to 27.9 dB.

Three months after the surgery, according to the SOCT data: MP is closed, blocked by a fragment of the ILM, the defect at the level of the outer segments of the photoreceptors and the ellipsoid and local detachment of the neuroepithelium in the projection of the fovea is reduced (height up to 76 μm, diameter up to 270 μm). BCVA is 0.5. Central MF is 29.1 dB. The point of visual fixation is in the center of the fovea. The patient subjectively noted an improvement in the quality of visual functions, distortions were practically not felt.

Six months after the operation, according to the SOCT data: the edges of the MP are adapted with preservation of the defect at the level of the ellipsoid zone of photoreceptors in the projection of the fovea with a width of 64 μm. Detachment of the neuroepithelium is not determined. The external limiting membrane is preserved along its entire length, has a linear profile. The MP is blocked by an inverted fragment of the ILM. BCVA is 0.7. According to microperimetry, the central SF increased to 31.1 dB.

During the 6-month observation period, no postoperative complications were observed.

Thus, the claimed method ensures a reduction in the number of intraoperative manipulations, performance of tamponade-free surgery with maintenance of a stable position of the ILM fragment, reliable blocking of the macular hole with the ILM fragment, closure of the MP with restoration of the normal histological architecture of the retina in the fovea, high functional treatment results, minimization of the risk of intra- and postoperative complications.

Claims (1)

A method for surgical treatment of primary through-and-through macular retinal hole, including formation of an upper invertible single-layer fragment of the internal limiting membrane (ILM), which is turned over and placed with the inner side on the macular hole (MP), while the ILM is not removed from other areas of the retina; then the fluid is replaced with air, in the air medium the ILM fragment is straightened on the surface of the retina, after which 2 drops of autologous platelet-poor plasma (PPP) are applied to the surface of the ILM fragment, then the PPP is exposed for 1 minute, then the retinal surface is dried with removal of the PPP and residual intraocular fluid, then 5 drops of PPP are applied to the surface of the fragment, exposure is carried out for 5 minutes, then the air is replaced with liquid.