Corneal transplantation (keratoplasty)

Keratoplasty (corneal transplant) is the main section in corneal surgery. Corneal transplant has different goals. The main goal of the operation is optical, i.e. restoration of lost vision. However, there are situations when the optical goal cannot be achieved immediately, for example, in severe burns, deep ulcers, long-term non-healing keratitis. The prognosis of transparent engraftment of the transplant in such patients is questionable. In these cases, keratoplasty can be performed for therapeutic purposes, i.e. for excision of 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, abundant vascularization and the transplant will not be surrounded by decaying corneal tissue. These two types of corneal transplant, different in their goals, differ little from each other in terms of the actual surgical technique. Therefore, in clinical practice, there are frequent cases when, after therapeutic keratoplasty, the transplant takes root transparently and the patient simultaneously experiences both a therapeutic and optical result.

Ameliorative corneal transplantation (keratoplasty) is a transplantation performed to improve the soil as a preparatory stage for subsequent optical keratoplasty. For tectonic purposes, the operation is performed for fistulas and other corneal defects. It can be considered that ameliorative and tectonic operations are types of therapeutic corneal transplantation.

Cosmetic corneal transplantation (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 cataract is excised with a trephine of the appropriate diameter and the resulting defect is replaced with a transparent cornea. If there are white areas on the periphery that are not captured in the trephine zone, they are masked with ink or soot using the tattoo method.

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

Based on fundamental differences in the surgical technique, a distinction is made between layer-by-layer and penetrating corneal transplantation.

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 cloudy cornea is cut off taking into account the depth of the opacities and their superficial borders. The resulting defect is replaced with a transparent cornea of the same thickness and shape. The transplant is reinforced with interrupted sutures or one continuous suture. In optical layered keratoplasty, centrally located round transplants are used. Therapeutic layered transplants of various types can be performed both in the center and on the periphery of the cornea within the affected area. The transplant can be round or of another shape.

The cornea of a human cadaveric eye is mainly used as donor material. For therapeutic layer-by-layer corneal transplantation, material preserved in various ways (freezing, drying, storage in formalin, honey, various balms, blood serum, gamma globulin, etc.) is suitable. If the transplant does not take root well, a repeat operation can be performed.

Penetrating corneal transplantation (keratoplasty) of the cornea is most often performed for optical purposes, although it can be both therapeutic and cosmetic. The essence of the operation is the penetrating excision of the central part of the patient's cloudy cornea and the replacement of the defect with a transparent transplant from the donor eye. The cornea of the recipient and donor is cut out with a round tubular trephine knife. The surgical kit includes trephines with a cutting crown of different diameters from 2 to 11 mm.

In the historical aspect, good results of penetrating keratoplasty were first obtained using small diameter transplants (2-4 mm). This operation was called partial penetrating keratoplasty and was associated with the names of Zirm (1905), Elschnig (1908) and V. P. Filatov (1912).

Transplantation of a large diameter cornea (more than 5 mm) is called subtotal penetrating keratoplasty. Transparent engraftment of a large transplant was first achieved by N. A. Puchkovskaya (1950-1954), a student of V. P. Filatov. Mass successful replacement of large corneal discs became possible only after the advent of microsurgical surgery techniques and the finest atraumatic suture material. A new direction in eye surgery emerged - reconstruction of the anterior and posterior segments of the eye based on free surgical access opened by wide trepanation of the cornea. In these cases, keratoplasty is performed in combination with other interventions, such as dissection of adhesions and restoration of the anterior chamber of the eye, iris plastic surgery and pupil repositioning, cataract removal, insertion of an artificial lens, vitrectomy, removal of a luxated lens and foreign bodies, etc.

When performing penetrating subtotal keratoplasty, good anesthetic preparation of the patient and extremely careful manipulation by the surgeon are required. Minor muscle tension and even uneven breathing of the patient can lead to the lens falling out into the wound and other complications, therefore, in children and restless adults, the operation is performed under general anesthesia.

A penetrating corneal transplant (keratoplasty), in which the diameter of the transplanted cornea is equal to the diameter of the recipient's cornea, is called total. This operation is practically not used for optical purposes.

The biological result of keratoplasty is assessed by the condition of the transplanted graft: transparent, translucent, and cloudy. The functional outcome of the operation depends not only on the degree of transparency of the graft, but also on the preservation of the optic nerve apparatus of the eye. Often, with a transparent graft, visual acuity is low due to the occurrence of postoperative astigmatism. In this regard, compliance with intraoperative astigmatism prevention measures is of great importance.

The best results can be achieved when performing operations on calm eyes that do not have a large number of vessels. The lowest functional indicators after surgery are observed with all types of burns, long-term non-healing ulcers and abundantly vascularized leukomas.

Corneal transplantation (keratoplasty) is part of a large general biological problem of organ and tissue transplantation. It should be noted that the cornea is an exception among other tissues subject to transplantation. It has no vessels and is separated from the vascular tract of the eye by intraocular fluid, which explains the relative immune isolation of the cornea, which allows keratoplasty to be successfully performed without strict selection of donor and recipient.

The requirements for donor material in penetrating keratoplasty are significantly higher than in layer-by-layer keratoplasty. This is explained by the fact that the penetrating transplant contains all layers of the cornea. Among them, there is a layer that is very sensitive to changing living conditions. This is the inner single-row layer of cells of the posterior corneal epithelium, which has a special, glial, origin. These cells always die first, they are not capable of full regeneration. After the operation, all structures of the donor cornea are gradually replaced by the tissues of the recipient's cornea, except for the cells of the posterior epithelium, which continue to live, ensuring the life of the entire transplant, which is why penetrating keratoplasty is sometimes called the art of transplanting a single-row layer of cells of the posterior epithelium. This explains the high requirements for the quality of donor material for penetrating keratoplasty and maximum caution in relation to the posterior surface of the cornea during all manipulations during the operation. For penetrating keratoplasty, a cadaveric cornea is used, preserved for no more than 1 day after the donor's death without preservation. Corneas preserved in special environments, including using low and ultra-low temperatures, are also transplanted.

In large cities, special eye bank services have been organized that collect, preserve, and control the storage of donor material in accordance with the requirements of existing legislation. Corneal preservation methods are constantly being improved. Donor material is necessarily examined for the presence of AIDS, hepatitis, and other infections; biomicroscopy of the donor eye is performed to exclude pathological changes in the cornea and to identify the consequences of surgical interventions in the anterior part of the eye.

Corneal transplant (keratoplasty) and rejection reaction

It is known that the decisive role in achieving success in transplantation of aplogic organs and tissues (including the cornea) is played by their compatibility with the recipient's organs and tissues in terms of HLA class II genes (especially DR) and HLA-B class I antigens, as well as mandatory immunosuppression. With complete compatibility in terms of DR and B genes and adequate immunosuppressive therapy after surgery (cyclosporine A is recognized as the optimal drug), the probability of transparent engraftment of the donor cornea is high. However, even with such an optimal approach, there is no guarantee of complete success; moreover, it is far from always possible (including for economic reasons). At the same time, numerous clinical cases are known when, without a special selection of a donor and recipient and without appropriate immunosuppressive therapy, a penetrating transplant engrafted perfectly transparently. This occurs mainly in cases where keratoplasty is performed on avascular leukomas, retreating from the limbus (one of the "immunocompetent" zones of the eye), if all the technical conditions of the operation are met. There are also other situations when the probability of an immunological conflict after the operation is very high. First of all, this applies to post-burn leukomas, deep and long-term non-healing corneal ulcers, abundantly vascularized leukomas formed against the background of diabetes and concomitant infections. In this regard, methods of preoperative immunological prediction of the risk of transplant rejection and postoperative monitoring (constant monitoring) are of particular relevance.

Among patients referred for keratoplasty, individuals with impaired immunity are especially common. For example, only 15-20% of patients with post-burn leukomas have normal immunological indices. Signs of secondary immunodeficiency are found in more than 80% of patients: half of them have predominantly systemic deviations, 10-15% have selective local shifts, and approximately 20% have combined disorders of local and systemic immunity. It has been established that not only the severity and nature of the burn, but also previous surgeries have a certain effect on the development of secondary immune deficiency. Among patients who have previously undergone keratoplasty or any other surgery on burned eyes, normoreactive individuals are found approximately 2 times less often, and combined immune disorders in such patients are detected 2 times more often than in previously unoperated patients.

Corneal transplantation may lead to aggravation of immune disorders observed before the operation. Immunopathological manifestations are most pronounced after penetrating keratoplasty (compared to layer-by-layer), repeated surgical interventions (on the same or fellow eye), in the absence of adequate immunosuppressive and immunocorrective therapy.

To predict the outcomes of optical and reconstructive keratoplasty, it is very important to monitor changes in the ratio of immunoregulatory T-cell subpopulations. A progressive 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 contribute to the development of systemic tissue-specific autoimmunization. An increase in the severity (before or after surgery) of autoimmune reactions directed against the cornea is usually associated with an unfavorable outcome. A recognized prognostic test is "inhibition" of leukocyte migration upon contact with corneal antigens in vitro (in RTML), indicating an increase in the 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 immune disorders, the type of keratoplasty, and the nature of pre- and postoperative conservative treatment. The peak is usually observed in the 1st to 3rd week after surgery. The risk of a biological reaction of the transplant in such cases increases significantly.

Testing of anti-corneal antibodies (in RIGA) is uninformative, which is apparently due to the formation of specific immune complexes.

Immunological prediction of keratoplasty outcomes is possible based on cytokine studies. Detection (before or after surgery) of IL-1b (responsible for the development of an antigen-specific cellular response) in the lacrimal fluid and/or blood serum is associated with a risk of transplant disease. This cytokine is detected in the lacrimal fluid only during the first 7-14 days after surgery and not in all patients (approximately 1/3). In serum, it can be detected much longer (within 1-2 months) and more often (up to 50% of cases after lamellar, up to 100% after penetrating keratoplasty), especially with insufficient immunosuppressive therapy. Detection of another cytokine, TNF-a (an IL-1 synergist capable of causing inflammatory, cytotoxic reactions), in the lacrimal fluid or serum is also a prognostically unfavorable sign. These facts should be taken into account when monitoring the effectiveness of the treatment and determining the duration of use of immunosuppressants that suppress the production of proinflammatory cytokines.

Despite the fact that the immunodeficiency state in patients with penetrating wounds and burns of the eye can be caused by hyperproduction of prostaglandins that suppress the secretion of IL-2 (one of the main inducers of the immune response) and the IFN-γ dependent on it, the administration of IL-2 (the drug Roncoleukin) or stimulants of its production during corneal transplantation is contraindicated, since they can cause activation of cytotoxic lymphocytes, resulting in an increased risk of transplant damage.

The patient's interferon status has a pronounced effect on the outcome of keratoplasty. An increase in the serum IFN-a concentration (up to 150 pg/ml and more), observed in every fifth patient with post-burn leukomas and 1.5-2 times more often after transplantation of the burned cornea (within 2 months), is associated with unfavorable outcomes of keratoplasty. These observations are consistent with data on the unfavorable pathogenetic significance of interferon hyperproduction and contraindications to the use of interferon therapy (in particular, recombinant a ₂ -interferon-reoferon) in 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 (IFN-a, IFN-b, IFN-y) and class II (IFN-y) molecules, to stimulate the production of IL-1 and, consequently, IL-2, thereby promoting the activation of cytotoxic lymphocytes, autoimmune reactions and the development of a biological reaction of the transplant with its subsequent turbidity.

Inability to moderately produce interferons (especially IFN-a, IFN-b), i.e. in concentrations required to protect against latent, chronic viral infections (often aggravated by immunosuppressive therapy), as well as hyperproduction of interferons, have an adverse effect on the results of keratoplasty. An example is observations of patients infected with the hepatitis B virus, for whom IFN-a deficiency is especially characteristic. In this group, the reaction of corneal transplant rejection was 4 times more frequent than in uninfected patients. These observations show that in patients with a defect in interferon formation, its moderate stimulation is advisable (in order to activate antiviral protection at the level of the whole organism) without undesirable enhancement of immunopathological reactions. Such treatment can be carried out in combination with immunosuppressive and symptomatic therapy using soft immunocorrectors with their systemic (but not local!) use.