Partial endothelial trepanation in addition to deep anterior lamellar keratoplasty in keratoconus patients. A randomized clinical trial.

Keratoconus is a progressive, non-inflammatory corneal disease in which
irregular refractive properties of the cornea result in loss of visual acuity.
Keratoconus usually arise in adolescence, is bilateral and has an estimated
incidence of 1:2000. The aetiology of keratoconus is largely unknown, genetic
predispositions are currently under investigation. Treatment is aimed at
improving vision, principally using (rigid) gas permeable contact lenses
(RGPs). With progression of the disease non-correctable refractive
abnormalities and/or corneal scars arise. For these advanced stages of
keratoconus, a corneal transplant is the only treatment modality.

The first corneal transplant for keratoconus was conducted in 1936 by Ramon
Castroviejo in New York*s Columbia Presbyterian Medical Centre. Ever since,
corneal grafting is subject to many technical developments. For over 70 years,
a technique is used in which a circular donor disc is cut with a trephine and
sutured in a concordantly prepared recipient, called a perforating keratoplasty
(PKP).

With the advent of refractive surgery in the years 1990, equipment appeared to
split a cornea in horizontal lamellae. This made partial thickness grafting
possible, tailoring grafts according to the nature and location of corneal
pathology. For keratoconus, only the affected anterior part of the cornea needs
to be transplanted. The posterior (endothelial) part is particularly involved
in graft rejections. The chance of graft rejection decreases significantly when
the patient*s endothelium is left in place.
For keratoconus, this new treatment modality is called a deep anterior lamellar
keratoplasty (DALK). The transplanted anterior corneal thickness is maximized,
and the patient retains its own endothelium and Descemet membrane, leading to
lower graft rejection rates. Theoretically, one could expect lower cataract
formation rates as well.

The biggest drawback of a DALK procedure is the risk of inadvertent
peroperative corneal perforation. The lamellae is cut too thick necessitating a
conversion to a complete thickness graft similar to a regular PKP. To prevent
inadvertent perforation, several techniques are described to dissect the stroma
from the posterior lying Descemet membrane and corneal endothelium.Failure and
perforation are described in 20% of cases though, leading to poor surgical
predictability and leaving the patient with an inferior end product.

To circumvent this problem we utilize a method in which, in addition to a DALK,
a partial endothelial trepanation (PET) is performed. This technique was first
performed by Busin, Villa Serena Hopsital, Forli, Italy. The endothelium is
loosened, but not transplanted. By doing this, the surgeon can retain safer
graft thickness margins leading to a lowered number of preoperative
perforations. The cornea is enabled to *mould* to the healthy donor curvature.
The addition of PET is believed to make corneal grafting safer and more
predictable.

To investigate the additional value of partial endothelial trepanation (PET) in
a deep anterior lamellar keratoplasty (DALK) procedure in terms of efficacy and
safety in patients with keratoconus.

A randomized controlled interventional parallel group patient-blinded trial.
Patients will be randomly assigned to either group A (addition of partial
endothelial trepanation to a deep anterior lamellar keratoplasty (PET+DALK
procedure) or group B (conventional DALK procedure).

Patients undergo, after thorough ophthalmic screening, a corneal grafting
procedure according to the DALK (deel anterior lamellar keratoplasty)
technique, with or without the addiation of the investigated PET (partial
endothelial trepanation) technique. The peroperative and postoperative care for
both treatmentgroups are identical.

The benefit for the keratoconus patient is regaining better visual acuity when
contact lens correction has become insufficient. Irregular astigmatism is the
main contributing factor for loss of visual acuity and can often be corrected
by rigid gas permeable contact lenses (RGPs) in early stages. With the
advancement of the keratoconus, the shape of the cornea prohibits proper
contact lens fitting, leading to contact lens intolerance. A keratoplasty will
reform the corneal curvature and will help in regaining good vision. Especially
in the case of corneal scarring in advanced keratoconus, corneal
transplantation is the only method to regain good clarity of the cornea. We
expect the modern PET+DALK procedure to surpass traditional keratoplasty in
terms of efficacy and safety.

The patient burden is comparable to the experiences of current transplant
methods used. Preoperatively, patients undergo a full ophthalmic screening. A
corneal transplant is performed under general anaesthesia and takes around
120-180 minutes. Postoperative checks are done at 1 day, 1 week, 2 weeks, 4
weeks, 6 weeks, 3 months, 6 months and annually thereafter. This control scheme
is in line with the guidelines of the Dutch Organ Transplantation Registry
(NOTR). The first weeks patients receive antibiotic / steroid eye drops in
decreasing frequency and will have to keep to certain precepts. These precepts
include, but are not limited to, refraining from heavy physical activities,
wetting of the eye and swimming for a certain amount of time. The inserted
corneal sutures are removed in two tempi, after 6 and 12 months.

Treatment risks do certainly exist, but are comparable with current transplant
methods. Short term side effects include postoperative wound infection, wound
dehiscence (necessitating suture removal or re-suturing), uveïtis, ocular
hypertension and hypersensitivity to ophthalmic medications. Long term risk
includes irregular astigmatism necessitating contact lens correction, cataract
formation, glaucoma, graft rejection, and graft failure.

Study participation or randomization have no effect on corneal graft selection
and quality.