A prospective multicenter clinical study to evaluate the safety and effectiveness of intrastromal implantation of the TransForm Corneal Allograft for providing near vision in presbyopic subjects
|Medical Monitor||Vance Thompson, MD|
|Address||Vance Thompson Vision 3101 W. 57th Street Sioux Falls, SD 57108 USA|
This is a prospective, single-armed, non-masked, non-randomized, multicenter, interventional, clinical trial. A maximum of 121 eyes of consecutive subjects will be enrolled and implanted with the TransForm Corneal Allograft (TCA) at up to 15 clinical sites.
The objective of this clinical study is to evaluate the safety and effectiveness of intrastromal implantation of the Allotex TCA for providing near vision in presbyopic subjects
Subjects must be presbyopic adults, needing from +1.75 D to +3.50 D of reading add in the non-dominant eye and must have uncorrected near visual acuity worse than 20/40 in the non-dominant eye.
Beginning in 1949 with the pioneering work of Jose Barraquer, there has been an interest in using natural corneal tissue to change the refractive properties of the eye. In recent years, non-allogenic, synthetic corneal implants have received marketing approval in the United Stated and Europe for refractive purposes. Although synthetic implants are made of biocompatible materials they are not equivalent to an allogenic implant in terms of biocompatibility. The Allotex TCA is a piece of acellular cornea, sterilized with electron beam radiation and shaped to a particular shape using a laser. The availability of precise laser shaping systems and sterile corneas are the key factors that make the use of allogenic implants possible.The TCA is applied under a femtosecond created corneal flap on a stromal bed. The goal is to enhance the visual performance of the patient with a material that is 100% biocompatible and precisely shaped for the individual’s needs.
Originally described in the early 1950s with more advanced work done in the 1980s, epikeratophakia is a form of refractive surgery where corneal tissue is lathed to an attempted specific dioptric power and sutured on top of the recipient’s cornea after the epithelium had been removed.Epikeratophakia was performed most extensively in the 1980s and has not been routinely used in the interim due the following limitations:
- Predictability of refractive power due to the problems with cryolathing preserved corneal tissue12,13;
- Difficulty of the preparing the lenticules14;
- Structural damage to the tissue during the required freezing and lathing process15,16;
- The thickness of the corneal lenticules increased the risk of epithelium ingrowth and poor re-epithelialization.6,17
Problems with the cryolathing process were later addressed by substituting an excimer laser for the corneal lathe removing the requirement for freezing the corneal tissue.18 The authors concluded that the excimer laser corneal shaping system allows a computer-controlled, surgeon- designed, sterile preparation of lamellar and penetrating corneal grafts which could offer significant advantages in comparison to presently available systems for lamellar dissection and trephination.
More recently, several non-allogenic corneal inlays have been developed to improve near vision in presbyopic adults. One iis constructed of a single piece of Polyvinylidene Fluoride formulated with carbon black pigment. Another is a hydrogel corneal inlay designed to be implanted permanently under a femtosecond-laser-created corneal flap onto the stromal bed of the cornea and centered over a light-constricted pupil.
The Allotex TCA addresses the historical limitations of epikeratophakia as well as corneal inlays as follows:
- Problems related to power and induction of astigmatism are mitigated by use of modern metrology and shaping techniques including use of an excimer laser system for shaping the TCA;
- Currently available shaping techniques will allow for creation of TCA that are significantly thinner than those used for epikeratophakia which will reduce the risk of epithelium ingrowth and problems with re-epithelialization;
- Due to the significant development and advancement in the technologies that will be used to shape the TCA, a variety of refractive treatments will be possible including for hyperopia and presbyopia.
- Since the TCA is acellular, sterile tissue donor immunogenicity is reduced.
- The procedure is easily reversible with the TCA being removed in a minimally invasive procedure.
The Allotex TCA is a formed lenticule comprised of sterile allogenic corneal tissue designed to alter the shape of the anterior surface of the cornea, thereby adjusting the point of focus on the retina. The tissue derives from human corneas, procured under strict ethical standards from an Eye Bank Association of America (EBAA) approved eye bank. After minimal processing by the eye bank the corneas undergo a validated electron beam (e-beam) sterilization process and are then transferred to Allotex for further processing.
The Allotex processing consists of slicing the cornea into sheets of various thickness, along the lamellar plane, using a micro-cryotome. These sheets are then further cut into discs using an appropriately sized biopsy punch, producing corneal blanks of a nominal thickness of 50 um and a 3.5 mm diameter. These corneal blanks are then placed in an environmentally controlled chamber to under excimer laser (wavelength 193 nm) shaping to produce the desired shape. All steps involving shape formation and changes of shape are monitored by high resolution optical coherence tomography (OCT) to insure that the lenticules are accurately produced. The formed lenticules then undergo an additional e-beam sterilization.
The lenticules are designed to be placed directly on top the recipient’s stroma which has been exposed by the creation of a thin, femtosecond laser created flap. After placement the flap is the laid down over the TCA and smoothed in the normal fashion. The final shape, after laser sculpting, is 2-3.5 mm in diameter, with a central thickness of 15-25 microns. The diameter is such that the patient is expected to have improved near and intermediate vision and will also retain distance vision from the rays entering the pupil around the periphery of the TCA.
Lions VisionGift, the provider of the Allotex allogenic tissue, procures, cleans and sterilizes cornea for shipment to Allotex. Terminal sterilization is performed by electron beam.
The TCA is indicated for intrastromal implantation to provide near vision in the non-dominant eye of presbyopic patients, 41 to 65 years of age, who have manifest refraction spherical equivalent of +1.00 diopters (“D”) to -0.75 D with ≤0.75 D of refractive cylinder, do not require correction for clear distance vision, but do require near correction of +1.75 D to +3.50 D of reading add.
Potential Adverse Events
The following have been identified as potential adverse events: ocular infection, epithelial ingrowth, loss of best spectacle corrected vision of > 2 lines, increase in intraocular pressure of > 10 mmHg to over 25 mmHg, diffuse lamellar keratitis, secondary surgical intervention, Allotex, Ineal haze, visual disturbances including double vision, glare and halos, corneal epithelial defect, problems associated with creation of the flap, corneal edema, foreign body sensations, pain, dry eye, increased astigmatism, corneal ectasia, corneal scarring, decentration of TCA, and TCA rejection.
Declaration of Helsinki
The study will be performed in accordance with the relevant recommendations guiding physicians in biomedical research involving human subjects adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 and later revisions.
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