Bowman layer transplantation for treatment of corneal contour deformations

Full-thickness keratoplasty is often complicated by high astigmatism,
suture-related problems, ineffective wound healing, and allograft rejection.
Fewer complications may be expected when only the diseased anterior or
posterior corneal layers are replaced by donor tissue, or when the cornea is
reinforced by addition of healthy tissue.

Recently, a new approach has been used for treating advanced progressive
keratoconus by implanting only an isolated Bowman layer (BL) graft in the
recipient*s mid-stromal pocket to remodel the corneal curvature. The obtained
reduction of ectasia was stable for at least up to 2 years after the
intervention. Advantage of transplanting only BL is that this is an acellular
corneal structure and the risk of allograft rejection is negligible. Even
though this technique proved to have a low risks of intraoperative
complications, inserting the BL transplant into a very thin corneal (advanced
keratoconus) is a challenging manoeuvre. In this study we want to investigate a
possibility to use a less invasive technique for implanting the BL, with the
aim to stabilize corneal contour deformations by fixating the graft onto the
cornea. The advantage of this technique is that the ocular integrity is largely
preserved with onlay BL graft positioning and, therefore, posterior scarring
related to inflammation is avoided.

To determine whether corneal stabilization can be achieved using a BL onlay and
minimize the risk of complications which occur during more invasive techniques.
This would also be a technically less demanding surgical procedure.

Cohort study.

44 consenting adult patients with corneal contour deformations will be
included.

All patients will undergo one experimental procedure in one eye.

Before the procedure, and at 1 day, 1 week, 1 month, 3 months, 6 months, 9
months, and 12 months, all eyes will be evaluated using slit-lamp
biomicroscopy, Pentacam imaging, specular microscopy, optical coherence
tomography (OCT), and confocal microscopy. Best corrected visual acuity and
complications will be documented at all examinations.

If necessary, patients will undergo an additional photorefractive keratectomy
(PRK) to correct corneal surface irregularities.

In the event of procedure failure, standard BL transplantation will serve as a
back-up procedure for given eye.

With the patient under local anesthesia, the corneal epithelium is removed. The
Bowman graft is immersed in 70% ethanol for 30 seconds to remove remnant
cellular material, thoroughly rinsed with balanced salt solution, and stained
with trypan blue (VisionBlue; DORC International BV). The Bowman graft is then
carefully positioned onto the host cornea, unfolded, and centered, using a
rigid contact lens to transfer the tissue. Tissue is fixated spontaneously by
dehydration and, if needed, extra donor tissue layers could be applied to
further stabilize the cornea. A soft contact lens is positioned onto the eye at
termination of the surgery. Postoperative medication includes topical
chloramphenicol 0.5% (6 drops daily for one week, then reduce to 2 drops daily
for an extra week and then stop) and dexamethasone 0.1% (4 drops daily for 1
month and then stop) and switch to fluorometholone 0.1% (4 drops daily up to 3
months and then taper by 1 drop every 3 months). Stop after 1 year.
The corneal epithelial wound healing process (a natural response of
regenerating tissue) will re-establish the integrity of the eye surface.

PRK is an established procedure and will be performed (if indicated) according
to standard protocol (Vestergaard 2014).

Benefits are that corneal contour deformations could be treated and stabilised
using minimally invasive procedure thereby avoiding the need of an intraocular
intervention, avoiding problems related to cell-containing grafts (rejection,
failure, detachments). The greatest advantage of this novel technique is the
fact that it only involves topical or local anaesthesia and can be performed
rather fast (compared to conventional transplants). Compared to the mid-stromal
BL transplantation, this novel experimental technique may cause less of a
burden for the patient, because the ocular integrity is largely preserved. The
restoration of the scraped epithelial cell layer is fast, leading to a possible
faster post-treatment recovery. Also, the recovery of the visual acuity is
expected to be quicker than with all currently available keratoplasty
techniques, since it is basically an 'extra-ocular' procedure with limited
effect on the eye's function. The risk of damaging the structure of the cornea
during procedure is very low because this is an extraocular procedure;
therefore there is no manipulation inside the eye.

Also, there is potential risk that epithelial cells may incompletely cover the
transplant. In case that this experimental *onlay* Bowman layer transplant
procedure does not give the desired results, the patient would need to undergo
a second operation, namely having a second Bowman Layer transplant inserted
inside a mid-stromal corneal pocket. We do not expect any negative effects of
having both transplants in-situ. However, re-operation poses a burden on
patients.

With PRK there may be low risk of damaging the cornea, although probably
smaller than normally, as in this case the laser treatment will probably not
reach the cornea of the patient because it is sheltered by the transplant(s).

Understanding the limitations and uncertainties of this new transplantation
procedure, we believe that benefits will outweigh the risks. Compared to more
invasive mid-stromal Bowman Layer transplantation, the novel experimental
technique may cause less of a burden for the patient, because the ocular
integrity is largely preserved. Also, the restoration of the scraped epithelial
cell layer is fast, leading to a possible faster post-treatment recovery.