Transplantation of the cornea (keratoplasty)

Keratoplasty (corneal transplantation) is the main section in corneal surgery. The transplantation of the cornea has a different target setting. The main purpose of the operation is optical, that is, restoration of lost vision. However, there are situations when the optical target can not be reached at once, for example, with severe burns, deep ulcers, which do not heal keratitis for a long time. The prognosis of transparent transplant engraftment in such patients is questionable. In these cases, keratoplasty can be performed for a therapeutic purpose, that is, for excising necrotic tissue and saving the eye as an organ. At the second stage, optical keratoplasty is performed on a calm cornea, when there is no infection, excessive vascularization and the graft will not be surrounded by a disintegrating tissue of the cornea. These two types of corneal transplantation, different in the target setting, do not differ much from each other in terms of the actual surgical technique. Therefore, in clinical practice, cases when after the therapeutic keratoplasty the transplant is transient is not uncommon, and the patient simultaneously has both a therapeutic and an optical result.

Meliorative corneal transplantation (keratoplasty) is a transplant performed to improve the soil as a preparatory stage for subsequent optical keratoplasty. With a tectonic purpose, surgery is performed for fistulas and other corneal defects. It can be considered that meliorative and tectonic operations are varieties of corneal transplantation.

Cosmetic transplantation of the cornea (keratoplasty) is performed on blind eyes, when it is impossible to restore vision, but the patient is confused by a bright white spot on the cornea. In this case, the throat is excised with trephine of the appropriate diameter and the defect is replaced with a transparent cornea. If there are white areas on the periphery that are not captured in the trepanation zone, they are masked with mascara or soot by the tattoo method.

Refractive corneal transplantation (keratoplasty) is performed in healthy eyes to alter the optics of the eye, if the patient does not want to wear glasses and contact lenses. The operations are aimed at changing the shape of the entire transparent cornea or just the profile of its surface.

On the basis of fundamental differences in the technique of surgery, a layered and through transplantation of the cornea is isolated.

Layered corneal transplantation (keratoplasty) is performed in cases where opacities do not affect the deep layers of the cornea. The operation is performed under local anesthesia. The superficial part of the turbid cornea is cut off taking into account the depth of the turbidity and their surface boundaries. The resulting defect is replaced by a transparent cornea of the same thickness and shape. The graft is strengthened with nodal sutures or with one continuous suture. Centrally located round grafts are used for optical stratified keratoplasty. Medical layer-by-layer transplants of different types can be produced both in the center and on the periphery of the cornea within the zone of its destruction. The graft can have a round and other shape.

As the donor material, the cornea of the human corpse eye is mainly used. For healing corneal transplantation, the material can be preserved in various ways (freezing, drying, storage in formalin, honey, various balms, blood serum, gamma globulin, etc.). If the transplant is turbidly engrafted, a second operation can be performed.

End-to-end transplantation of the cornea (keratoplasty) of the cornea is most often performed with an optical purpose, although it can be both curative and cosmetic. The essence of the operation consists in the through excision of the central part of the muddy cornea of the patient and replacement of the defect with a transparent graft from the donor eye. Cutting out the cornea of the recipient and the donor is made with a round tubular knife-trephine. In the surgical set there are trephines with a cutting crown of different diameters from 2 to 11 mm.

In a historical aspect, good results of through keratoplasty were first obtained using small diameter grafts (2-4 mm). This operation was called partial through keratoplasty and was associated with the names of Cyrram (1905), Elshniga (1908) and VP Filatov (1912).

Transplantation of a large diameter cornea (more than 5 mm) is called subtotal through keratoplasty. Transplant engraftment of a large transplant was first obtained by NA Puchkovskaya (1950-1954) - a pupil of VP Filatov. Mass successful replacement of large corneal discs became possible only after the appearance of microsurgical technique of operation and the finest atraumatic suture material. A new direction in eye surgery has arisen: the reconstruction of the anterior and posterior segments of the eye on the basis of free operative access, which opens with wide trepanation of the cornea. In these cases, keratoplasty is performed in combination with other interventions such as dissection of the adhesions and restoration of the anterior chamber of the eye, iris plastic and pupillary repositioning, removal of cataracts, introduction of an artificial lens, vitrectomy, removal of the lenticular lens and foreign bodies,

When performing throughtotal keratoplasty, a good anesthesia preparation of the patient and extremely careful manipulation of the surgeon are required. A slight strain of the muscles and even uneven breathing of the patient can lead to the loss of the lens to the wound and other complications, so in children and troubled adults, the operation is performed under general anesthesia.

The transverse corneal transplantation (keratoplasty), in which the diameter of the transplanted cornea is equal to the diameter of the cornea of the recipient, is called total. With the optical purpose, this operation is practically not used.

The biological result of keratoplasty is assessed by the condition of the transplanted graft: transparent, translucent and turbid. The functional outcome of the operation depends not only on the degree of transparency of the transplant, but also on the safety of the optic-nervous apparatus of the eye. Often, in the presence of a transparent transplant, visual acuity is low due to the occurrence of postoperative astigmatism. In this regard, the importance of meeting the measures of intraoperative prevention of astigmatism.

The best results can be obtained when performing operations on quiet eyes that do not have a large number of vessels. The lowest functional parameters after the operation are noted in all types of burns, long-term healing ulcers and profusely vascularized leukomas.

Transplantation of the cornea (keratoplasty) is part of a large general biological problem of transplantation of organs and tissues. It should be noted that the cornea is an exception among other tissues to be transplanted. It has no blood vessels and is separated from the vascular tract of the eye by intraocular fluid, which explains the relative immune isolation of the cornea, which makes it possible to successfully perform keratoplasty without strict selection of the donor and recipient.

The requirements for the donor material for through keratoplasty are significantly higher than for layered keratoplastics. This is because the through graft contains all layers of the cornea. Among them there is a layer very sensitive to changing living conditions. It is an internal single-row layer of cells in the posterior epithelium of the cornea, which has a special, glial, origin. These cells always die first, they are not capable of full-fledged regeneration. After the operation, all structures of the donor cornea are gradually replaced by the tissues of the cornea of the recipient, except for the cells of the posterior epithelium, which continue to live, providing the life of the entire graft, therefore, through keratoplasty is sometimes called the art of transplantation of a single row of cells of the posterior epithelium. This explains the high quality requirements of the donor material for through keratoplasty and maximum care with respect to the posterior surface of the cornea with all manipulations during the operation. For through keratoplasty, a corpse cornea is used, which is stored for no more than 1 day after the death of the donor without preservation. The cornea is also transplanted, preserved in special media, including low and ultra-low temperatures.

In the large cities, special services of eye banks are organized, which take the collection, conservation and control over the storage of donor material in accordance with the requirements of existing legislation. Methods of preservation of cornea are constantly being improved. Donor material is necessarily examined for the presence of AIDS, hepatitis and other infections; carry out biomicroscopy of the donor's eye in order to exclude pathological changes in the cornea, to reveal the consequences of surgical interventions in the anterior part of the eye.

The transplantation of the cornea (keratoplasty) and the rejection reaction

It is known that their compatibility with the organs and tissues of the recipient for the genes of HLA class II (especially DR) and HLA-B class I antigens, as well as mandatory immunosuppression, play a decisive role in achieving success in the transplantation of theplastic organs and tissues (including the cornea). With full compatibility with the DR and B genes and conducting adequate immunosuppressive therapy after surgery (ciclosporin A is the optimal agent), the probability of a transparent engraftment of the donor cornea is high. However, even with such an optimal approach, there is no guarantee of total success; in addition, it is far from always possible (including for economic reasons). At the same time, numerous clinical cases are known where, without special selection of the donor and the recipient and without appropriate immunosuppressive therapy, the transplant transplant was perfectly transparent. This occurs mainly in cases where keratoplasty is performed on avascular lining, having receded from the limb (one of the "immunocompetent" zones of the eye), if all the technical conditions of the operation are observed. There are also other situations when the probability of an immunological conflict after surgery is very high. First of all, this refers to post-burn fenestrains, deep and long-term healing corneal ulcers, abundantly vascularized leukemias, which are formed against the background of diabetes and concomitant infections. In this connection, the methods of pre-operative immunological forecasting of the risk of graft rejection and post-operative monitoring (constant monitoring) become of particular relevance.

Among patients referred to keratoplasty, especially those with immunity disorders are common. So, for example, only 15-20% of patients with post-burned belly detect normal immunological parameters. Signs of secondary immunodeficiency are found in more than 80% of patients: half of them - mainly systemic abnormalities, 10-15% - selective local shifts, about 20% - combined disorders of local and systemic immunity. It was found that not only the severity and nature of the burn suffered, but also the surgical interventions made earlier, have a certain influence on the development of secondary immune deficiency. Among patients who had previously undergone keratoplasty or some other operation on burned eyes, normo-reactive individuals occur about 2 times less often, and the combined immunity disorders in such patients are revealed in 2 times more often than in previously not operated patients.

Transplantation of the cornea can lead to aggravation of immunity disorders that were observed before the operation. Immunopathological manifestations are most pronounced after a through keratoplasty (in comparison with layered), repeated surgical interventions (on the same or a pair eye), in the absence of adequate immunosuppressive and immunocorrective therapy.

To predict the outcomes of optical and reconstructive keratoplasty, monitoring of changes in the ratio of immunoregulatory subpopulations of T cells is very important. Progressing increase in the blood content of CD4 ⁺ lymphocytes (helpers) and a decrease in the level of CD8 ⁺ cells (suppressors) with an increase in the CD4 / CD8 index promotes the development of systemic tissue-specific autoimmunization. The increase in the expression (before or after the operation) of autoimmune reactions directed against the cornea is usually associated with an unfavorable outcome. A recognized prognostic test is the "inhibition" of migration of leukocytes in contact with corneal antigens in vitro (in RTML), indicating the enhancement of a specific cellular immune response (a key immunological factor in transplantology). It is detected with varying frequency (from 4 to 50% of cases), depending on previous immunity disorders, the type of keratoplasty, the nature of pre- and postoperative conservative treatment. The peak is usually noted at 1-3 weeks after surgery. The risk of a biological graft reaction in such cases is significantly increased.

The testing of anti-coronary antibodies (in RIGA) is not very informative, which, apparently, is due to the formation of specific immune complexes.

Immunological prediction of outcomes of keratoplasty is possible on the basis of the study of cytokines. Detection (before or after surgery) of tear and / or serum IL-1b (responsible for the development of antigen-specific cellular response) is associated with the threat of graft disease. In the lacrimal fluid, this cytokine is detected only in the first 7-14 days after the operation and not in all patients (about 1/3). In the serum, it can be detected much longer (within 1-2 months) and more often (up to 50% of cases after layer-by-layer, up to 100% - after through keratoplasty), especially with insufficient immunosuppressive therapy. A prognostically unfavorable sign is also the detection in the lacrimal fluid or serum of another cytokine - TNF-a (synergist IL-1, capable of causing inflammatory, cytotoxic reactions). These facts should be taken into account when controlling the effectiveness of the treatment and determining the duration of the use of immunosuppressants that suppress the production of proinflammatory cytokines.

Despite the fact that the immunodeficiency state in patients with penetrating wounds and eye burns can be due to hyperproduction of prostaglandins that inhibit the secretion of IL-2 (one of the main inducers of the immune response) and its dependent IFN-y, the appointment of IL-2 (Roncoleukin) or stimulants of its products during corneal transplantation are contraindicated, since they can cause activation of cytotoxic lymphocytes, which increases the risk of graft damage.

The pronounced influence on the outcome of keratoplasty is exerted by the interferon status of the patient. An increase in the concentration of IFN-a in the serum (up to 150 pg / ml and more) observed in every fifth patient with post-burn fenestoms and 1.5-2 times more often after the transplantation of the burned cornea (within 2 months) is associated with adverse outcomes of keratoplasty . These observations are consistent with data on the unfavorable pathogenetic role of interferon hyperproduction and contraindications to the use of interferon therapy (in particular, recombinant a ₂ -interferon-rheferon) in the transplantation of other organs and tissues. The immunopathological effect is due to the ability of interferons of all types to enhance the expression of HLA class I molecules (IFN-a, IFN-p, IFN-y) and class II (IFN-y), stimulate production of IL-1 and, consequently, IL-2, thereby promoting the most activation of cytotoxic lymphocytes, autoimmune reactions and the development of the biological response of the graft followed by its turbidity.

The inability to moderate production of interferons (especially IFN-a, IFN-b), i.e., in concentrations necessary to protect against latent, chronic viral infections (often exacerbated by immunosuppressive therapy), as well as hyperproduction of interferons, have an unfavorable influence on the results of keratoplasty. An example is the observation of patients infected with the hepatitis B virus, for which the deficiency of the INF is particularly characteristic. In this group, the rejection reaction of the corneal transplant was 4 times more frequent than in uninfected patients. These observations show that in patients with a defect in interferon formation, it is reasonable to moderate it (with the goal of activating antiviral protection at the level of the whole organism) without unduly strengthening immunopathological reactions. Such treatment can be carried out in conjunction with therapy with immunosuppressive and symptomatic means with the help of soft immunocorrectors with systemic (but not local!) Their application.