Technical Field
The invention relates to the technical sector of medical devices intended for the long-term storage of a cornea, in particular for grafting, or for ex vivo experimentation on human or animal cornea.
Description of the Related Art
Depending on the state of the technique, cornea grafts are stored throughout the world mainly in two different manners: either at +4° C. for a short period (maximum 10 days) using a technique called cold storage, or according to a technique called organ culture at a temperature ranging from +31° C. to +37° C. Organ culture uses a nutrient medium derived from cell culture media that allows a long-term storage of up to five weeks. It is a sequential technique including an initial phase during which the cornea becomes oedematous (its thickness is multiplied by two, going from 500-600 μm to 1000-1200 μm) and folds over on its posterior face, and a second phase over 12 to 72 hours during which the graft is immersed in the same organ culture medium but with an added macromolecule (Dextran T500 or poloxamer 188) which diminishes the turgidity of the graft to reduce its thickness and decrease the posterior fold right before graft.
In both of these techniques the grafts are immersed either in simple glass or plastic bottles in which the cornea is free, or in boxes where the cornea is partially immobilized in a cage or basket (like a contact lens case). In both cases there is no circulation of the storage medium, nor maintenance of a pressure gradient on either side of the cornea.
However, in order to be stored in an optimal manner, the graft must be in conditions similar to those found in its physiological environment. The physiological parameters to be reproduced are specifically those of the anterior chamber of the eye, i.e., intra-ocular pressure of the order of 18 millimeters of mercury (mmHg) and a temperature of the order of 31 to 37° for a human eye for example, and the circulation of a cornea storage liquid both on the endothelial side (mimicking the permanent renewal of the aqueous humor) and on the epithelial side (mimicking the permanent circulation of tears). If these conditions are not reproduced, the cornea cells death is accelerated especially in the posterior fold zones and the corneal stroma becomes oedematous and there is a transient loss of its transparency.
U.S. Pat. No. 5,789,240 describes a cornea assembly device that simulates the anterior chamber of the eye. This device allows reproducing the intra-ocular pressure, temperature and intraocular liquid circulation parameters but it is solely intended for laboratory experimentation to carry out drug penetration tests. This device does not allow storing corneal grafts prior to cornea transplant in a patient. In particular, it does not allow the sterile circulation of preservation liquid on both sides of the cornea, i.e., both the epithelial and endothelial sides. It is not fully transparent to allow examining the cornea without opening the device. Therefore, the survival time of the cornea has to be short and is incompatible with using it for a cornea transplant.
French Patent No. 2944185 describes a “perfusion chamber” for corneas designed to be in a vertical position only, to mimic the flow of tears. This perfusion chamber is also intended for laboratory experiments, in particular preclinical toxicity studies but not for the storage of corneal grafts before transplant. It comprises an endothelial compartment designed to be filled with gel to keep the shape of the cornea but does not include any circulation of nutrient liquid on the endothelial side. It does not include a pressure gradient maintenance system on either side of the cornea. It is not transparent throughout.
The article from British Journal of Ophthalmology 2001; 85:450-3 “A simple corneal perfusion chamber for drug penetration and toxicity studies” presents a polycarbonate chamber developed to receive a human cornea, however it has only been tested with pig and cat cornea. It includes a closed circuit liquid circulation set into motion by a peristaltic pump. The 18 mmHg pressure gradient is maintained by gravity (bottle containing the perfusion liquid placed at a height). The corneal epithelium is in contact with the ear and the epithelial compartment is not airtight. It is not transparent throughout. This perfusion chamber is not intended for the storage of cornea specimens prior to transplant either.
Furthermore, none of the previous art devices allow flattening the cornea to allow LASER cutting of the corneal tissue or facilitating the observation of endothelial cells on a flat surface. In the current state of the art, the cornea are cut with a femtosecond LASER on specific supports which are not appropriate for the storage of grafts. In the prior state of the art, the grafts had to be extracted from their storage medium, manually placed on a specific support exposed to ambient air and then placed under the LASER cutting system. To flatten the cornea another device must be attached to the actual LASER and not to the corneal specimen support.
Finally, none of the prior art devices claims the possibility of performing a graft cell therapy.
Concerning the use of prior art devices for ex vivo experiments on the penetration of molecules and toxicity studies, none of them combines the following characteristics: allow a sterile storage of human or animal cornea on the long-term (several weeks), include a pressure gradient on the endothelial side, include the circulation of liquid on both sides of the cornea, being transparent throughout and having a cornea flattening device.