Corneal limbal stem cell transplantation is a breakthrough in ophthalmology, as it can restore vision in patients who have had thermal or chemical burns to the surface of the eyes, for example as a result of a firecracker or lime burn. The treatment methods used so far have not always been effective, and have been associated with numerous complications.

A corneal limbal stem cell transplantcan restore vision in patients who have had their corneal cells damaged by chemical burns or thermal trauma.

The cornea is the convex, transparent, blood vessel-free layer that covers the front of the cornea. In a he althy person, the anterior corneal epithelium is constantly replaced (damaged or aging) and replaced (every 3 to 10 days) due to the presence of corneal limbal stem cells (this is a narrow, transitional zone about 1 mm wide, located at the edge of the cornea, conjunctiva and sclera).

Damage to this area, e.g. as a result of chemical or thermal factors, may lead to neovascularization, i.e. the appearance of blood vessels, the growth of the conjunctiva on the cornea, reduction of the transparency of the cornea and significant deterioration of vision. The accompanying symptoms are pain, photophobia, tearing, blepharospasm, chronic inflammation and redness of the eye

The consequence of corneal damage is the deficiency or failure of limbalstemcelldeficiency (LSCD) stem cells and loss of transparency, which is associated with loss of vision.

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Secondary and acquired limbal stem cell deficiency

Deficiency or failure of limbal stem cells can be either congenital or acquired. Primary, is very rare and is associated with congenital absence of iris and KID syndrome including: corneal keratopathy, ichthyosis, deafness, erythokeratoderma, and sclera.

Secondary limbal insufficiency (KRM) is mainly associated with burns of the surface of the eye (thermal and chemical, often resulting from an accident at work).

This group also includes: Stevens-Johnson syndrome, wearing contact lenses, corneal infections, neoplastic lesions, peripheral ulcerative diseasescornea or neurotrophic keratopathy (related to damage to the nerves supplying the cornea).

The degree of damage to the corneal limbus of stem cells is determined primarily on the basis of a clinical history or biomicroscopic examination (slit lamp). The diagnosis can be supported by a Pap smear (impression cytology).

Corneal limbal stem cell transplant - what is it?

What is the treatment like when there is a thermal or chemical burn to the cornea? In the initial phase of treatment, the focus is on maximum protection of damaged tissues and support of the regenerative process. Conservative treatments include supportive care, reduction of inflammation, removal of dead tissue, and the use of an amniotic dressing, and their effects depend on the presence of stem cells that have survived the injury or disease.

If there are no stem cells available, transplant is the only treatment option. Until now, corneal limbal stem cells could be obtained from a second, he althy eye, from a related donor, or from a deceased one. These treatments are financed by the National He alth Fund.

However, the above-mentioned methods of treatment are associated with long-term treatment, lifelong use of immunosuppressive drugs (in the case of allogeneic transplants), high risk of transplant rejection, serious complications, and they do not always bring the expected results.

The situation is different in the case of the latest method, which involves transplanting corneal epithelial stem cells from a he althy eye of the patient, cultured in a laboratory.

After a transplant, stem cells produce the cell epithelium throughout their lives.

A new treatment option, a transparent circular plate made of living autologous human corneal epithelial cells containing limbal stem cells.

To obtain such a plate, a small portion (1-2 mm sq) of he althy limbal tissue should be collected. This is very little, considering that for CLAU (Autologous Limbal Transplantation), approximately 20 mm kw of limbal biopsy must be obtained.

The next stage is the cultivation of stem cells under special controlled conditions in a certified laboratory, where they are "nourished" and multiplied for about half a year.

The grown material undergoes a series of serological and bacteriological tests and is transported in an appropriate container to the medical facility where the transplant will take place. It is worth knowing that the journey can only take place by land. Pressure variation that occurs during flightby plane, it could destroy the cells.

Corneal limbal stem cell transplant as an autologous transplant reduces the risk of rejection by the patient, and there is no need to administer immunosuppressants for life.

Before transplantation, the damaged surface tissue of the cornea should be removed. The operated eye is protected with patches for four days. It is worth noting that during this time, doctors do not administer any medications. On the fifth day, the epithelium that covers the surface of the eye can be seen using an optical coherent tomograph. For the next two weeks, doctors still do not administer medications to the patient, e.g. eye drops, which contain substances that could damage or destroy the transplant.

- This procedure is revolutionary due to the fact that we only need a very small fragment of the corneal limbus from a he althy eye, so the risk of its damage is practically zero. The old method, in which we needed a larger cut, also works and it is not bad, but it was associated with this risk, which now does not exist - says Prof. dr hab. n. med. Elisabeth Messmer from the Ludwig and Maximilian University in Munich.

The distinguishing feature of this therapy is that the transplant contains multiplied, appropriate stem cells. In the case of other transplant techniques, we do not know what cell pool we are transplanting.

This method is called a breakthrough in ophthalmology, as it enables the effective treatment of diseases for which until recently there were no effective therapies.

- We can heal with it, e.g. double-sided blindness, i.e. not only injuries or diseases of one eye. Besides, also other types of pathologies, autoimmune diseases, Stevens-Johnson syndrome - lists prof. Augusto Pocobelli, director of U.O.C. Ophthalmology, Banca degli Occhi Azienda Ospedaliera S. Giovanni Addolorata.

Limbal stem cell therapy is aimed at adult patients with moderate or severe limbal stem cell deficiency in one or both eyes due to thermal or chemical burns to the eyes.

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Techniques for stem cell transplantation

  • autologous corneal conjunctival limb transplant (CLAU)

the procedure involves collecting the conjunctiva andlimb from the second, he althy eye (a he althy eye can donate 40% of stem cells without risking it). This technique has no risk of rejection. However, it should be remembered that CLAU disqualifies patients with bilateral disease and carries the risk of damaging the he althy eye, from which a large amount of material has to be collected. It also happens that after corneal limbus transplantation, a cornea transplant must be performed in order to improve the quality of vision.

  • allogeneic corneal and conjunctival limb transplant from a living relative (LR-CLAL)

Compared to the previous method, it enables the treatment of the disease not only unilaterally, but also in a situation where both eyes are affected. Unfortunately, this procedure carries a high risk: rejection of the transplant; serious side effects; transmission of infectious diseases, as well as the development of neoplastic diseases due to the long-term use of immunosuppressive drugs; damage to the eye of the person from whom the implantation material is taken. Due to the fact that the procedure is based on the removal of tissue from another person, there is a risk of transplant failure and the administration of immunosuppressive drugs is necessary. It is worth emphasizing that it is often impossible to perform such a transplant due to the lack of relatives who would qualify for the procedure.

  • allogeneic corneal limbal transplant from a deceased donor (KLAL).

The procedure allows for obtaining a large number of stem cells and is mainly performed in bilateral treatment, although it can also be used in the case of damage to one eye. Compared to the LR-CLAL transplant, the KLAL method does not allow for the collection of the conjunctiva. Therefore, it is used in patients whose disease mainly affects the corneal limbus, with no or little involvement of the conjunctiva. The main risk for the patient is the rejection of the transplant, and with it the use of immunosuppressive drugs. As in the case of LR-CLAL, there is a risk of transmission of infectious diseases, as well as the development of neoplastic diseases due to the long-term use of immunosuppressants.

  • mixed grafts (LT-CLAL and KLAL, CLAU and KLAL

in case of damage to the corneal limbus of stem cells, a mixed transplant (LR-CLALi KLAL, CLAU and KLAL) can also be performed. One of the advantages of this technique is the possibility of using deceased and living donor material, increasing the treatment options for severe conjunctival and limbal injuries. The disadvantages of a mixed graft are: KLAL does not allow the collection of a large part of the conjunctiva, while LR-CLAL and CLAU give a limited amount of limbal tissue.(insufficient quantity and quality of transplant material).

  • transplant of cultured corneal epithelial stem cells from a he althy eye of the patient

The latest method involves transplanting corneal epithelial stem cells from a he althy eye of the patient, cultured in a laboratory.

Corneal limbal stem cell transplant in Poland

Currently, in patients with limbal stem cell deficiency, there is no other effective, approved treatment option to restore vision. It is estimated that in Poland, approximately 30-40 patients per year would be eligible for the procedure using corneal limbal stem cells.

However, the modern method of corneal limbal stem cell transplantation is not covered by the reimbursement in Poland. Currently, it is only available in the form of clinical trials.

The therapy has been registered as ATMP, i.e. a medicinal product of advanced medical technology. This means that it has passed the full registration process in the field of GMP, GLP, GCP, meeting the requirements of EU law.

It is currently reimbursed in Italy, France, Great Britain, the Netherlands and Belgium. It is worth noting that it is one of the few advanced therapy medicinal products (ATMPs) that is covered by public funding for the above-mentioned. European Union countries.

It is worth adding that this therapy is in line with the "Plan of the Minister of He alth for 2022 for the government administration department: He alth", according to which it is planned to develop transplant medicine and increase access to highly specialized he althcare services financed from the state budget .

Corneal limbal stem cell transplantation operations are currently carried out in 17 centers around the world. Among them, the team of Polish doctors led by prof. dr hab. n. med. Edward Wylęgała from the Medical University of Silesia.

One of the goals contained in the "Plan" for 2022 is "a gradual increase in the number of organ transplants", which is to be performed in particular by: preparation of biostatic transplants, cell culture and financing the collection and storage of allogeneic cord blood as well as by financing of innovative techniques in the field of tissue, cell and organ transplantation.1

The procedure is also in line with the assumptions of the Multiannual Program for 2011-2020 "National Program for the Development of Transplant Medicine". The main assumption of this "Program" is "striving to get closer to the indicatorsEuropean Union in terms of the number of organ, tissue and cell transplants ", with specific assumptions including:" 4. increasing the number of donations and transplants of the cornea "and" 7. implementation of new types of transplantation of organs, cells and tissues as well as development of transplantation programs in groups of recipients at higher risk. " 2

A breakthrough in the treatment of people with thermal and chemical eye burns. A corneal limbal stem cell transplant can restore their eyesight

Source: Biznes.newseria.pl

The publication was created as part of the "Miracle of vision - saving eyesight" campaign.