RU2833147C1 - Method of performing through keratoplasty with native donor cornea - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology, and can be used for surgical treatment of purulent and trophic ulcers, vascularised leukoma and outcomes of degenerative-dystrophic processes of both the recipient's own cornea and the previously transplanted cornea. That is ensured by replacing the injured cornea with a through native donor graft. Eyeballs are extracted from the donor with the stated brain death and the extraocular eye muscles and the optic nerve are transected. Further, eyeballs are placed in sterile containers at temperature of 4-8 °C and for no more than 3 hours delivered to the ophthalmological centre. In an ophthalmic hospital environment, donor cornea suitability for transplantation is assessed for no more than 5 hours. For this purpose, when performing biomicroscopy, corneal transparency, absence of signs of previous operations and other pathological processes are assessed; endothelial microscopy – density of corneal endothelial cells, presence of hexagonal shape and uniform size of corneal epithelium; adrenaline test – the state of the pupil is inspected under a slit lamp at time intervals of 5, 10, 15 minutes after instillation on the surface of cornea of 2-3 drops of 0.1% solution of epinephrine hydrochloride. If the donor cornea is suitable for transplantation, a through corneal transplantation is performed within next 12 hours. In the operating room, after a two-minute exposure of the donor material in an aqueous solution of povidone iodine 1%, followed by abundant irrigation of the donor material with sterile 0.9% NaCl solution, method involves cutting out a corneoscleral disc and trepanation of a native donor cornea with diameter of 8.0 to 9.0 mm, not more than 0.25 mm of a recipient bed. Trepanation and subsequent excision of the recipient's tissue is performed at a distance of at least 0.25 mm from the area of the affected corneal tissue, followed by suturing the previously cut out donor graft. Latter is sutured with interrupted and/or continuous sutures with 10-0 nylon sutures into the recipient’s bed prepared in advance. Further, an ophthalmic solution of BSS is introduced into the anterior chamber of the recipient until normalization.

EFFECT: invention provides high anatomical and functional result of surgical intervention, high probability of transparent engraftment of graft and reduced risk of postoperative complications due to high functional activity of endothelium of native donor tissue.

2 cl, 1 tbl, 3 ex

Description

The invention relates to medicine, namely to ophthalmology, and is intended for the surgical treatment of purulent and trophic ulcers, vascularized leukomas and outcomes of degenerative-dystrophic processes of both the recipient's own cornea and a previously transplanted cornea, with the aim of both emergency eye rescue (with an organ-preserving purpose) and subsequent optical-reconstructive operations.

In many cases, with the development of purulent and trophic ulcers, vascularized leukomas and outcomes of degenerative-dystrophic processes, drug treatment is ineffective. The only way to save the eye, with a subsequent chance to restore vision is penetrating corneal transplantation.

Today, thanks to the development of microsurgical techniques and drug therapy, it is possible to perform penetrating corneal transplantation even in cases of severe inflammatory infections and dystrophic processes. However, in most cases, the operation is performed using donor cornea kept in a preservative solution [1], but the results of this corneal transplantation remain unfavorable - keratotransplant disease occurs in 65-70% of patients [2].

The closest analogue is the corneal transplantation method [3], in which a bed for the transplant is formed up to the Descemet membrane, the donor cornea is cut out and the donor transplant is placed in a previously prepared recipient bed with an intact Descemet membrane. This method is not applicable to patients with purulent-inflammatory changes in the recipient's stroma for technical reasons, as well as due to the need for a complete replacement of the affected cornea in order to eliminate the infectious focus.

Known methods of corneal transplantation do not describe performing a full-thickness (throughout the entire thickness) transplantation with native donor cornea, but describe the use of preserved or cadaveric corneal grafts.

The method of using native donor cornea that we propose is characterized by a high level of preservation of the endothelium of the donor cornea, since the extraction of the eyeballs is performed in donors with preserved blood circulation and oxygenation (donors with brain death) and corneal transplantation is performed in a fairly short time from the moment of collecting the donor material in the first 20 hours, which ensures high functional results, as well as transparent engraftment of the corneal transplant, due to the preservation of the endothelial cells of the donor tissue, including in recipients of the “high risk” group of corneal transplant disease.

It is believed that acute inflammation in the recipient's eye during surgery (the so-called "hot transplant") significantly predisposes to transplant disease due to non-immunological reasons. However, in a number of cases: corneal ulcer with perforation, trauma with loss of corneal tissue, corneal infiltrates - performing penetrating corneal transplantation for recipients is the only way to save the eye. Transparent engraftment is the most important factor in high visual acuity in the operated eye. In connection with the above, the state of the endothelium, given the lack of regenerative capacity of the latter, is decisive in corneal transplantation.

The pathogenesis of endothelial cell loss in transplant disease is complex, associated with many mechanisms, and studies on endothelial cell regeneration are in the early stages [4]. In this regard, the development of methods to ensure the preservation of endothelial cells during penetrating corneal transplantation is relevant. The absence of a period of exposure of the native donor cornea to a preservation solution ensures a short period of “shock period” - the time when the endothelium is in vitro. In a high-tech ophthalmological center and with extensive experience of the microsurgeon, this period can be less than 60 seconds (the moment from the removal of the corneoscleral disc to placing the transplant in a pre-prepared recipient bed). All of the above ensures protection of the endothelial cells of the transplant, which significantly increases the likelihood of transparent engraftment - a favorable outcome - of penetrating transplantation of the native donor cornea.

The objective of the invention is an effective and functionally promising implementation of penetrating transplantation of native (non-preserved) donor cornea of the eye removed from a donor with preserved blood circulation and oxygenation (brain-dead donors).

Unlike similar methods, the developed method solves the problem due to the fact that eyeballs are collected from donors with preserved blood circulation and oxygenation (donors with brain death), followed by examination and transplantation to the recipient in a fairly short time; this method is available in a hospital setting, provides high functional indicators of the procedure of transplantation of native donor cornea, the implementation of which, in many clinical situations, is the only way to save the recipient's eye, as well as to obtain a high functional result.

The invention is based on the results of a study of more than 250 patients who underwent 285 penetrating keratoplasties.

Diagnoses of patients who underwent penetrating keratoplasty

(n=285)

Clinical diagnoses Number of cases Share in % Corneal ulcer 87 30% EED 77 27% Corneal leucorrhoea 62 22% Keratoconus 40 14% Hereditary corneal dystrophies 19 7% Total 285 100%

The essence of the present invention is that, on a working heart, after cerebral death has been established in donors with preserved blood circulation and oxygenation (donors with brain death), the eyeballs are extracted by cutting the extraocular eye muscles and the optic nerve. The eyeballs are then placed in sterile containers at a temperature of 4–8 °C and delivered to an ophthalmology center within no more than 3 hours. In an ophthalmology hospital, the native donor cornea is analyzed within no more than 5 hours for suitability for penetrating keratoplasty, using:

- biomicroscopy: evaluates the transparency of the cornea, the absence of signs of previous operations and other pathological processes;

- use of an endothelial microscope: the density of corneal endothelial cells is more than 2500 mm², hexagonal shape and uniform size of 20-25 µm;

- biochemical method: adrenaline test[5]. 2-3 drops of official 0.1% solution of adrenaline hydrochloride are instilled onto the surface of the cornea. The initial time of the test is noted. At time intervals of 5, 10, 15 minutes, the condition of the pupil is examined under a slit lamp. If the onset of deformation of the pupil towards mydriasis is detected (change in shape and size along at least one of the meridians), the reaction is considered positive, and the reaction time is complete. If the onset of the pupil's reaction to adrenaline is 5 minutes, the test is considered sharply positive and corresponds to grade A viability of the cells of the tissues of the anterior segment of the eye (including the cornea); if the reaction time is 10 minutes, the test is assessed as positive and corresponds to grade B; if the reaction time is 15 minutes, the test is considered conditionally positive and corresponds to grade C. If there is no pupillary reaction within intervals of up to 15 minutes, the test is considered negative, and the native donor cornea is energetically non-viable.

Upon establishment of suitability, within no more than 20 hours from the moment of collection, penetrating corneal transplantation is performed: in operating room conditions, after a two-minute exposure of the donor eyeball to an aqueous solution of 1% povidone iodine, followed by irrigation of the donor eyeball with a sterile solution of 0.9% NaCl, the corneoscleral disc is cut out and trepanation of the native donor cornea with a diameter of 8.0 to 9.0 mm is performed no more than 0.25 mm from the recipient bed; trepanation and subsequent excision of the recipient tissue are performed at a distance of at least 0.25 mm from the area of the affected corneal tissue. The native donor cornea is sutured with interrupted and/or continuous sutures with 10-0 nylon thread into a previously prepared recipient bed. Next, ophthalmic solution BSS is introduced into the anterior chamber of the recipient until normotension is achieved.

The essence of the proposed method is explained by the following clinical examples:

Example 1. Donor R., 24 years old, diagnosed with blunt traumatic brain injury, severe traumatic brain contusion, SAH, cerebral edema, dislocation syndrome, was declared brain dead on 18.01.2021 at 23:45. Eyeballs were collected and transported under sterile conditions at a temperature of (4-8 °C) and the material was handed over to the MGOC staff at 02:12 on 19.01.2021. At 07:00 on 19.01.2021, the donor cornea was deemed suitable for transplantation. A decision was made to transplant the native donor cornea to recipient H., 26 years old, who was undergoing treatment at the MGOC with a diagnosis of corneal infiltrate, post-traumatic keratoiridocyclitis of the left eye. At 14:10 on 19.01.2021, penetrating keratoplasty was performed with native donor material using the developed method from the above-mentioned donor. Given the presence of a 7.5 mm wide corneal infiltrate, the donor cornea was cut out with a diameter of 8.25 mm and sutured to the recipient bed with a diameter of 8.0 mm with interrupted sutures (given the risk of cutting through, with subsequent failure, of a continuous suture) with a 10-0 nylon thread. Despite the fact that the operation belonged to the category of “high risk” of graft disease, the postoperative period was uneventful. The inflammation was stopped conservatively, the sutures were removed after 12 months. On the 472nd day, at the control examination, the graft is transparent, visual acuity of the left eye is 0.7 n / k. The example demonstrates a high functional result of the proposed method of penetrating corneal transplantation with native donor material.

Example 2. Donor P., 60 years old, diagnosed with cerebral infarction on 26.05.2021, left middle cerebral artery syndrome, stage 3 hypertension, risk of cardiovascular complications 4, occlusion of the left internal carotid artery, was declared brain dead on 28.05.2021 at 15:45. Eyeballs were collected and transported under sterile conditions at a temperature of (4-8 ° C) and the material was handed over to the MGOC staff at 18:12 on 28.05.2021. After confirming the suitability (at 22:12 on 28.05.2021) of donor corneas for transplantation, a decision was made to transplant native donor corneas. Recipient E., 25 years old, who was treated at the Moscow Regional Eye Center with a diagnosis of corneal ulcer with perforation of the right (only seeing eye) underwent penetrating keratoplasty with native donor material from the above-mentioned donor using the developed method at 08:35 on 28.05.2021. The operation was performed for organ-preserving purposes. Considering the presence of corneal perforation and an 8.0 mm wide area of infected tissue, the donor cornea was cut out with a diameter of 8.5 mm and sutured into the recipient's bed with a diameter of 8.25 mm using interrupted and continuous sutures with 10-0 nylon thread. The operation belonged to the category of "high risk" graft disease, the postoperative period was uneventful. The inflammation was stopped conservatively, the sutures were removed after 16 months. When examined after 27 months, the transplant is transparent, visual acuity of the right eye is 0.9 n/c. Even when using native donor material, in cases of corneal transplants for organ-preserving purposes, the presented method ensures a high functional result due to the preservation of the endothelium of the transplanted cornea.

Example 3. Donor Sh., aged 36, with a diagnosis of closed craniocerebral injury, severe brain contusion, subdural hematoma of the right hemisphere with a volume of 65 ml. traumatic subarachnoid hemorrhage, soft tissue contusion of the left parietal region was declared brain dead at 21:40 on 13.10.2021. The eyeballs were collected and transported under sterile conditions at a temperature of (4-8 ° C) and the material was transferred to the MGOC staff at 01:12 on 14.10.2021. After confirming the suitability (at 04:05 on 14.10.2021) of the donor corneas for transplantation, a decision was made to transplant the native donor cornea. Recipient P., 48 years old, who was treated at the Moscow Regional Eye Center with the diagnosis of corneal ulcer with perforation of the left eye, luxation of the lens into the anterior chamber, choroidal detachment, underwent penetrating keratoplasty with native donor material using the developed method from the above-mentioned donor at 15:35 on 14.10.2021. The operation was performed for organ-preserving purposes. Considering the presence of corneal perforation and an 8.5 mm wide area of infected tissue, the donor cornea was cut out with a diameter of 9.0 mm and sutured into the recipient's bed with a diameter of 8.75 mm using interrupted and continuous sutures with 10-0 nylon thread. The operation belonged to the category of "high risk" graft disease, the postoperative period was uneventful. The inflammation was stopped conservatively. When examined after 10 months, the transplant is transparent.

Thus, the developed method for performing penetrating keratoplasty with a native donor cornea ensures the preservation of the endothelium of the transplanted cornea, which increases the transparency of the transplant engraftment.

Sources of information taken into account when preparing the description of the application for an invention:

1. Application for invention No. 2007101966/15, dated 19.01.2007.

2. Yildiz EH, Hoskins E, Fram N, Rapuano CJ, Hammersmith KM, Laibson PR, Cohen EJ. Third or greater penetrating keratoplasties: indications, survival, and visual outcomes. Cornea. 2010 Mar;29(3):254-9. doi: 10.1097/ICO.0b013e3181b31b6f. PMID: 20118784.

3. Patent for invention No. 95117002 dated September 19, 1995.

4. Baturina G.S., Katkova L.E., Solenov E.I., Iskakov I.A. Restoration of corneal endothelial function (literature review) // Siberian Scientific Medical Journal. 2019. No. 3.

5. Patent for invention RU No. 2070009 dated 17.03.1993.

Claims (6)

1. A method for performing penetrating keratoplasty with native donor cornea, which consists in the fact that, on a working heart, after establishing brain death in donors with preserved blood circulation and oxygenation - donors with brain death, the eyeballs are collected and transported to the clinic within no more than 3 hours, in a sterile container under hypothermia; then, within no more than 5 hours, the native donor cornea is analyzed for suitability for penetrating keratoplasty, using: - biomicroscopy: evaluates the transparency of the cornea, the absence of signs of previous operations and other pathological processes; - endothelial microscope: corneal endothelial cell density is more than 2500 ^mm2 , hexagonal shape and uniform size of 20-25 µm; - biochemical method: adrenaline test, for which 2-3 drops of official 0.1% solution of adrenaline hydrochloride are instilled onto the surface of the cornea; the initial time of the test is noted; at time intervals of 5, 10, 15 minutes, the condition of the pupil is examined under a slit lamp; if the onset of deformation of the pupil towards mydriasis is detected: changes in shape and size along at least one of the meridians - the reaction is considered positive, and the reaction time is complete; if the onset of the pupil's reaction to adrenaline is 5 minutes, the test is considered sharply positive and corresponds to grade A viability of tissue cells of the anterior segment of the eye, including the cornea; if the reaction time is 10 minutes, the test is assessed as positive and corresponds to grade B; in the case of a reaction time of 15 minutes, the test is considered conditionally positive and corresponds to grade C; if there is no pupillary reaction within intervals of up to 15 minutes, the test is considered negative, and the native donor cornea is energetically non-viable; if suitability is established within no more than 20 hours from the moment of collection, a penetrating corneal transplant is performed: in an operating room, after a two-minute exposure of the donor eyeball to an aqueous solution of 1% povidone iodine, followed by irrigation of the donor eyeball with a sterile solution of 0.9% NaCl, the corneoscleral disc is cut out and trepanation of the native donor cornea with a diameter of 8.0 to 9.0 mm is performed no more than 0.25 mm from the recipient bed; trepanation and subsequent excision of the recipient tissue are performed at a distance of at least 0.25 mm from the area of the affected corneal tissue, followed by suturing of the previously cut native donor cornea into the previously prepared recipient bed; then, BSS ophthalmic solution is injected into the anterior chamber of the recipient until normotension is achieved. 2. The method according to item 1, characterized in that the suturing of the native donor cornea is carried out with interrupted and/or continuous sutures using 10-0 nylon thread.