Patent Application
20120226286
Embodiments of this invention relate to a system and method for handling and inserting a corneal implant (also referred to as a donor cornea or lenticule) into the eye of a recipient without inducing significant endothelial damage.
A paradigm shift in the approach to corneal transplantation is occurring, with new forms of anterior and posterior lamellar keratoplasty now enabling targeted replacement of only diseased layers of the cornea. These forms of lamellar corneal surgery are gradually replacing conventional full thickness penetrating keratoplasty (Tan D T, Mehta J S: “Future Directions in Lamellar Corneal Transplantation”; Cornea; October 2007; Volume 26; pp S21-S28).
Descemet's stripping automated endothelial keratoplasty (DSAEK) is a form of small incision and essentially sutureless surgery which represents the latest innovation in a series of posterior lamellar keratoplasty procedures that are now synonymous with the term “endothelial keratoplasty”. The DSAEK procedure involves stripping of diseased Descemet's membrane and endothelial cells through a small corneal incision, and replacement with a posterior lamellar donor corneal lenticule prepared with the use of the Automated Lamellar Therapeutic Keratoplasty (ALTK) unit (Price M O, Price F W Jr.: “Descemet's stripping with endothelial keratoplasty: comparative outcomes with microkeratome-dissected and manually dissected donor tissue”; Ophthalmology; 2006 November; 113(11):1936-42).
With the adoption of any new surgical technique there is an inevitable learning curve for the surgeon and an accompanying evolution in techniques (see, for example: Price F W, Price M O: “Descemet's stripping with endothelial keratoplasty in 200 eyes: Early challenges and techniques to enhance donor adherence”; J Cataract Refract Surg. 2006; 32(3):411-8; Melles G R, Lander F, Beekhuis W H, Remeijer L, Binder P S: “Posterior lamellar keratoplasty for a case of pseudophakic bullous keratopathy”; Am J Ophthalmol. 1999 March; 127(3):340-1; Melles G R, Lander F, Nieuwendaal C: “Sutureless, posterior lamellar keratoplasty: a case report of a modified technique”; Cornea; 2002 April; 21(3):325-7; Melles G R, Wijdh R H J, Nieuwendaal C P: “A technique to excise the Descemet membrane from a recipient cornea (descemetorhexis)”; Cornea; 2004 April; 23(3):286-8; Terry M A, Ousley P J: “Replacing the endothelium without corneal surface incisions or sutures: the first United States clinical series using the deep lamellar endothelial keratoplasty procedure”; Ophthalmology; 2003 April; 110:755-64; discussion 764).
One of the most challenging aspects of this procedure is the insertion of the donor posterior lenticule into the anterior chamber (AC) through a small incision, without inducing significant endothelial damage. The current widely performed technique requires insertion of the donor lenticule through a small 5 mm corneal or scleral incision by folding the lenticule and gripping the folded tissue with non-compressing forceps i.e. ‘taco insertion’. This traumatic handling of the donor has been criticized because of its propensity for damaging endothelial cells, with primary graft failure rates due to intraoperative endothelial cell loss and damage ranging from 6% to 45% in the current literature with this folding technique (Mearza A A, Qureshi M A, Rostron C K: “Experience and 12-month results of Descemet-stripping endothelial keratoplasty (DSEK) with a small-incision technique”; Cornea 2007 April; 26(3):279-283). Damage to endothelial cells may occur as a consequence of mechanical folding of the donor, compression with holding forceps, and may also occur during intraocular manipulations to unfold the donor within the AC without the presence of an ophthalmic visco-surgical device (OVD). More recently, laboratory models of DSAEK have shown that folding of the donor lenticule for insertion into the AC and intraocular manipulation to unfold the donor is the stage most associated with significant endothelial cell loss (Lee W B, Sy H M, Holley G P, Edelhauser H F: “Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK): Intra-Operative Effects on the Donor Corneal Endothelium”; IOVS supplement; 2007; abstract 1131). The endothelial damage is worse in the presence of associated anterior chamber shallowing.
Our own extensive in-vitro work has confirmed that significant endothelial damage occurs with the conventional folding technique, despite the use of commercially available ‘non-compression’ forceps (Goosey forceps, model no. 19090, Moria, Antony, France). Damage primarily occurring as a consequence of direct contact of folded endothelial surfaces where the folding forceps are applied, as well as along the folding crease (Mehta J S, Por Y M, Beuerman R W, Tan D T: “Glide Insertion Technique of Donor Cornea Lenticule during Descemet's Stripping Automated Endothelial Keratoplasty”; J Cat Refract Surg; in press). Our recent studies show that the mean endothelial cell loss is 39% with this technique, which is now described:
A 1 mm paracentesis is first made in the peripheral cornea opposite a 5 mm temporal scleral tunnel wound (for insertion of intraocular forceps). A standard, commercially available anterior chamber intraocular lens (IOL) Sheet's glide is trimmed to 4 mm in width along approximately half to ⅔ of its length. Using Kelman Macpherson forceps, the glide is inserted into the AC through the scleral tunnel, with the right hand, whilst a balanced saline solution (BSS) infusion is maintained on. The donor (both the anterior and posterior lamellae) is transferred to a Paton's spatula. A dispersive OVD is liberally applied over the endothelial surface particularly the peripheral circumference of the donor. Carefully gripping the posterior donor lamellar with Kawai intraocular capsulorhexis forceps (Asico) on the stromal side, the anterior cap is slid away from the spatula, ensuring that the posterior donor lamella stays on the spatula. OVD is placed on the anterior surface of the glide, and the Paton spatula with the posterior lenticule is carefully everted, corneal endothelial surface down, onto the OVD-covered portion of the glide. Holding the glide with the right hand with Kelman Macpherson forceps at its most posterior part, the left hand, passes the Kawai forceps through the paracentesis, across the AC and over the sheets glide, and is passed out through the scleral incision. The Kawai forceps is rotated, so that the forceps teeth are now obliquely or vertically aligned, and can be used to grasp the leading edge of the donor lamella, on the upper stromal surface. Once the forceps grasped the donor edge, the donor is rapidly pulled through the scleral incision in one steady, smooth motion until the donor is fully in the AC. At the same time, the glide was retracted out of the eye.
We have performed this technique in 24 cases of DSAEK surgery, with only one primary graft failure occurring (4.2%). This contrasts with our previous 20 cases using the folding technique which had primary graft failure rate of 25% (5 eyes). Our scanning electron microscope (SEM) studies confirm that significant reduction in endothelial loss occurs with this technique, with a mean cell loss of 9%, mostly occurring at the peripheral rim, which may be due to contact of the donor edges with the plastic sheets glide, despite the use of OVD, and some damage must still occur when the donor is dragged through the lips of the wound, as the donor endothelial surface is still potentially in contact with the inferior lip of the scleral wound. We have not encountered any cases of donor dislocation with this technique, although we have now seen one case of partial Descemet's detachment. Our only primary graft failure occurred during our first case using this technique and can be attributed to the use of an excessively thick donor lenticule (400 μm) which resulted in Descemet's detachment.
Recently, a new technique called Descemet's Membrane Endothelial Keratoplasty (DMEK) has been developed. In this endothelial keratoplasty technique, an isolated an isolated Descemet's membrane is transplanted. This technique is even more difficult than DSAEK surgery, since an isolated Descemet's membrane is even thinner and more fragile than one which is supported by one or more layers of endothelial cells.
A previous system and method developed by the present Applicants in order to facilitate DSEAK surgery is described in WO2009/050511, and further in US2010/0211051, the full contents of each of which is hereby incorporated into the present application by reference. This system for donor cornea implantation includes a preparation base having a well for receiving a donor cornea, a cartridge disengageably mounted on the base adjacent the well, and a handle for disengageable attachment to a posterior end portion of the cartridge. In drawing the donor cornea from the well into and through a bore or chamber of the cartridge, from the posterior end, the donor cornea is caused to assume a double coil configuration. After attachment of the handle, removal of the assembly from the preparation base, and insertion of a blade and adjacent body portions of the cartridge through an incision in the recipient's cornea, the coiled donor cornea is pulled from the cartridge chamber, through its forward end, to uncoil automatically within the anterior chamber of the recipient's eye. While effective, it is believed that there is still room for improvement.
Embodiments of the invention may seek to provide an apparatus and method for inserting an endothelial corneal implant (which may be a donor implant harvested from a cadaver, or alternatively an artificial endothelial implant) into the eye of a recipient without inducing significant endothelial damage. The endothelial implant may comprise an isolated Descemet's membrane, or a Descemet's membrane supported on one or several layers of endothelial cells. The endothelial implant may also be referred to as a donor cornea or lenticule.
Further embodiments of the invention may seek to provide such an apparatus and method wherein and whereby the donor cornea is temporarily deformed for effective insertion, while providing protection against significant endothelial damage.
Viewed from a first aspect, the present invention provides a system for use in preparing a lenticular or corneal implant, in particular but not exclusively an endothelial corneal implant, for delivery to an operating site and insertion into a recipient's eye, the system comprising:
The cartridge may comprise attaching structure adjacent a rearward end of said tubular portion for disengageable attachment to a handle.
The system may further comprise a handle having a gripping portion and means adjacent one end for disengageable attachment to said disengageable attachment structure of said cartridge, said handle, when attached, enabling facile manipulation of said cartridge.
The upper portion of said base may be constructed to accommodate said handle when it is assembled with said engaged cartridge.
The attachment means of said handle may engage said attachment structure of said cartridge in only a single orientation of relative rotation about a longitudinal axis.
The attachment means of said handle engages attachment structure of said cartridge in a snap-fit relationship.
The handle may have closure structure at said one end thereof, constructed to engage said tubular portion of said cartridge and to thereby produce a liquid-tight seal of said normally open rearward end of said bore of said tubular portion.
The gripping portion of the handle may have opposite sides, and indicia may be provided on at least one of said opposite sides of said gripping portion to distinguish it from the other side thereof.
At least one of said cartridge and said funnel structure may have structure for inducing inward curling of opposite lateral edges of the implant in the course of passing from said platform to said forward end of said bore of said cartridge.
The narrower end of the funnel structure of the insert member may define an aperture similar in cross-sectional area to the cross-section of the longitudinal bore or the cartridge.
The funnel structure may further include a first ridge element extending longitudinally along at least a portion of funnel structure proximate the narrower end thereof and projecting inwardly thereinto. The ridge element may serve to induce curling of lateral edges of the implant during longitudinal movement therealong from the wider end to the narrower end and into the longitudinal bore of the cartridge.
Alternatively or in addition, the longitudinal bore of the cartridge may include a second ridge element extending longitudinally along at least a portion of the bore and projecting inwardly thereinto from the sidewall and serving to induce curling of lateral edges of the implant during longitudinal movement therealong.
Where both first and second ridge elements are provided, these should be in general positional registration with each other when the insert member and the cartridge are assembled onto the preparation base, and of generally similar cross-sectional shape and/or size where ends of the first and second ridge elements face each other.
The insert member may have a saddle-shaped configuration, adapted to straddle and snugly engage the recess in the upper portion of the preparation base. Viewed in an alternative manner, the insert member may have a bridge-type structure, with a spanning portion and two leg portions. The spanning portion bridges the preparation base, and the leg portions engage on either side of the preparation base. Outer parts of the leg portions may be provided with finger grips to facilitate placement and removal of the insert member on or from the preparation base.
The platform of said insert member may cooperate with platform structure defined on the upper portion of said preparation base so as to provide a generally dish-shaped receptacle for receiving the implant. In other embodiments, the platform of said insert member by itself defines a generally dish-shaped receptacle for receiving the implant. The system may include two or more insert members that define dish-shaped receptacles of differing depths or curvatures so as to accommodate different thicknesses of implant. For some surgical procedures, for example, it is desirable to use a very thin single lenticule comprising just endothelial tissue, whereas other procedures may require a thicker double lenticule comprising a full thickness graft of thickness 80 to 120 μm.
The cartridge may have a blade portion extending forwardly from said sidewall beyond said forward open end of said bore. The blade portion may be suitable for insertion into an incision in a corneal surface of a recipient eye.
The cartridge will advantageously be integrally formed, as a single piece, and will desirably be moulded from a substantially transparent or translucent synthetic resinous material. The ridge element where provided will normally be formed with convexly curved lateral surfaces extending along its length and terminating in a common longitudinal apex. At the forward end of the tubular portion of the cartridge the sidewall will desirably be formed with a transaxial bevel that declines toward the blade portion, to facilitate physical access into the bore and insertion of the forwardmost part of the body portion into the recipient's cornea. The curvilinear cross section of the bore will normally be generally circular or generally elliptical, and the bore will generally be of uniform cross-section along at least a major portion of its length.
The structure for inducing bilateral curling of a donor cornea may comprise a ridge element extending longitudinally along the bore of the cartridge and/or in the funnel structure, as described. Additionally, there may be provided a pair of laterally spaced shoulder elements, having curl-inducing surfaces facing one another and disposed substantially at the intersection of the dish-shaped receptacle and the cartridge-receiving structure (taking the form, for example, of curved surfaces forming a U-shaped throat section). Normally, the cartridge-receiving structure of the preparation base will coact slideably with structure of the cartridge in such manner that the cartridge can be received in only a single orientation of rotation about its longitudinal bore, and usually the cartridge-receiving structure and the attaching structure will permit receipt of the cartridge by relative movement in only one direction, and disengagement by relative movement only in the opposite direction.
The lower portion of the preparation base may be flat so as to stand on a surface such as a worktop without wobbling. The lower portion of the preparation base may include a flange and/or finger grips so as to allow it to be held firmly on the worktop without slipping.
Viewed from another aspect, the present invention provides a method of preparing a lenticular or corneal implant, in particular but not exclusively an endothelial corneal implant, prior to surgery, using the system described above, comprising the steps:
Optionally, the method may further comprise the step of:
The implant may be an endothelial corneal implant, in which case it is supported adjacent the open rearward end of the longitudinal bore with its endothelial side uppermost, and cause to adopt a double coil configuration within the longitudinal bore with the endothelial surface on the inside of the double coil, so as to provide a degree of protection from damage.
In use, an endothelial corneal implant is placed, endothelial surface facing upwardly, in position adjacent the open rearward end of the longitudinal bore of the tubular portion of the cartridge; the donor cornea is drawn into the bore, to reside therein, by force applied from the open forward end of the bore, for example by pulling the implant into the cartridge by way of forceps which have been introduced at the forward end of the bore and through the cartridge. As the implant is drawn through the funnel structure, opposed edges of the implant curl inwardly and the implant maintains a double-curl configuration within the bore of the cartridge. Once the implant is fully within the cartridge, the forceps are released, and the handle is attached to the cartridge using the means described.
During subsequent surgery, the cartridge may be positioned, using the attached handle, so that the blade portion enters an incision and provides a platform along which the implant may glide into the anterior chamber of a recipient eye. The implant is typically drawn through the forward open end of the cartridge bore into the anterior chamber of the recipient's eye using forceps.
During surgery, an opening (incision or paracentesis) is formed in the cornea of a recipient, at least at generally diametrical locations; followed by inserting the blade portion and the adjacent part of the body portion of the cartridge through one of the openings, inserting a gripping portion of an instrument through another opening in the cornea so as to grip an edge of the implant adjacent the open forward end of the cartridge bore; and pulling the implant into the anterior chamber of the recipient eye. The method may include the step of causing the implant to assume a double coil configuration, with no endothelial surface areas in mutual contact with one another, in the course of drawing the implant into the bore of the cartridge.
Viewed from a further aspect, there is provided a cartridge for effecting coiling and insertion of a donor cornea implant, comprising a generally tubular portion including a sidewall defining a longitudinal bore, of curvilinear cross section, having open forward and rearward ends; a blade portion extending forwardly from said sidewall beyond said forward open end of said bore; and structure adjacent a rearward end of said tubular portion for disengageable attachment to a handle; wherein the sidewall of the cartridge includes a portion that is tapered from the rearward end to the forward end, such that the longitudinal bore has a greater cross-section at the rearward end than the forward end.
In some embodiments, the cartridge may further comprise a ridge element extending longitudinally along at least a portion of said bore and projecting inwardly thereinto from said sidewall, said ridge element being constructed to induce inward curling of opposite lateral edges of a donor cornea during movement therealong.
In some embodiments, an outer surface of the sidewall may be provided with ridges, ribs, grooves or other structure to help to retain the cartridge in place when inserted through an incision into the anterior chamber of a recipient's eye.
By tapering the structure of the cartridge from its rearward end to its forward end, it is possible to provide a large enough opening at the rearward end to facilitate insertion in coiling of the donor cornea implant as described hereinabove, while allowing the forward end and the blade portion to be narrower than hitherto possible. When making an incision into the surface of an eye, for example into the anterior chamber, it is better for the incision to be made as small as possible. This is because the anterior chamber (and indeed the eye itself) has a tendency to invert or turn inside out due to internal pressure if too large an incision is made.
Moreover, by providing external ribs or grooves or ridges on at least a portion of the outer surface of the sidewall, it is possible to design the cartridge so that it tends to stay in place when inserted into the anterior chamber of an eye through a small incision and will tend to resist extrusion due to pressure from the inside of the anterior chamber. The ribs or grooved or ridges are preferably configured to as to be substantially parallel to the sides of the incision when the cartridge is inserted into the anterior chamber.
Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to”, and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.
Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.
The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.
For a better understanding of the present invention and to show how it may be carried into effect, reference shall now be made by way of example to the accompanying drawings, in which:
The preparation base 12 is symmetrical about a longitudinal centreline, and includes a bottom flange portion 18 and an upstanding pedestal portion 20, each of which is provided with gripping elements 22, 24, respectively. It will be noted that the flange portion 18 has the word CORONET, designated 90′, moulded into it so as to the project above the adjacent surface; apart from its literal significance, the structure forming the word provides texture to further facilitate secure gripping of the base.
An implant-receiving recess or well 28, formed in the top wall of the pedestal portion 20 of the preparation base 12, and complemented by a platform 101 formed in a saddle- or bridge-shaped insert member 100, which will be described in more detail below. A relatively wide trough 39, of arcuate cross section, is also formed in the top wall of the pedestal portion 20 and extends rearwardly from the well 28.
A pair of lugs 48 extend laterally inwardly toward one another at the top of the pedestal portion 20, and define the upper margins of a passage 37 between the well 28 and a channel 42. The lugs 48 serve to engage with and releasably retain the cartridge 16 as shown. A further pair of lugs 480 on the top of the pedestal portion 20 serve to engage with and releasably retain the handle 14 when engaged with the cartridge 16 as shown best in
As shown best in
A glide member 74 (in the form of a blade or tongue-like element) extends forwardly from the anterior end 70 of the sidewall of the body 62 and is of generally planar form (oriented, in a crosswise direction, parallel to the major elliptical axis of the chamber 64). Stepped flanges, generally designated by the numeral 76, are formed along the opposite sides of the cartridge body 62, each flange 76 consisting of an anterior element 78 and a posterior element 79, the end faces of which posterior elements 79 are coplanar with the generally annular surface 68 surrounding the posterior end opening 66. A catch element 80 is formed at the posterior end of the cartridge 16, between the flange elements 79, and provides means for disengageably securing the cartridge 16 to the handle 14 when the components are properly assembled with one another, as will be described presently.
As best seen in
The ridge or protrusion 82, where provided, is complementary to the ridge or protrusion 108 in the funnel structure 105 of the insert member 100 when the insert member 100 and the cartridge 16 are properly assembled onto the preparation base 12 as shown in
As shown best in
When the cartridge 16 is fully engaged with the handle 14, a finger 110 is disposed within the bore 64 of the cartridge 16, with an apical portion 86 of the ridge 82 seated in the groove 112 along the finger 110. A first wall portion 114 near the inner end of the slot bears upon the proximate end of the ridge 82, and a second wall portion 116 bears upon the confronting portion of the annular surface 68 at the posterior end of the cartridge bore 64. This structure produces an effective liquid-tight seal at the posterior end of the cartridge, which is held in assembly therewith due to the snap-fit engagement of the tab 99 on the prong 98 of the handle collar 96 in front of the catch 80 on the cartridge 16 (the tab having a bevel to facilitate assembly, and the prong 98 being sufficiently resiliently deflectable to enable disassembly, as appropriate).
Use of the system of
The implant “D” is then drawn through the posterior end opening 66 of the body 62 of the cartridge 16 and into its bore 64, using forceps “F” introduced through the anterior opening 70 to grip the stromal edge and apply a pulling force thereupon, as indicated by the open arrows in
When the implant “D” is drawn fully into the chamber 64 (as depicted in
After the implant “D” is loaded into the cartridge, the assembly is removed from the preparation base 12 (by a rearwardly sliding action), turned right-side up and, in the initial phase of implantation, the blade element 74 and adjacent cartridge body portion are introduced through the scleral tunnel of the anterior chamber so as to form a complete seal of the wound; this phase is depicted in
Thus, it can be see that embodiments of the present invention provides an apparatus and method for preparing a corneal implant for implantation into the eye of a recipient without inducing significant endothelial damage. In accordance with the apparatus and method described, the implant is only temporarily deformed, for effective insertion, while protection against significant endothelial damage is afforded. It might be pointed out that, in its double coil configuration, corresponding opposite lateral portions of the implant need not be in mutual registration; useful results may be achieved when, for example, the implant is deformed to a 60:40 ratio of asymmetry in the double coil configuration.
A glide member 374 (in the form of a blade or tongue-like element) extends forwardly from the anterior end 370 of the sidewall of the body 362 and is of generally planar form (oriented, in a crosswise direction, parallel to the major elliptical axis of the chamber 364). Stepped flanges, generally designated by the numeral 376, are formed along the opposite sides of the cartridge body 362, each flange 376 consisting of an anterior element 378 and a posterior element 379. A catch element 380 is formed at the posterior end of the cartridge 316, between the flange elements 379, and provides means for disengageably securing the cartridge 316 to the handle 14 when the components are properly assembled with one another.
As best seen in
The ridge or protrusion 382, where provided, is complementary to the ridge or protrusion 108 in the funnel structure 105 of the insert member 100 when the insert member 100 and the cartridge 316 are properly assembled onto the preparation base 12 as shown in
Of particular note with respect to the cartridge 316 is that the tubular body 362 tapers inwardly from the rearward end 366 to the forward end 370, at least along a portion thereof. The diameter or cross-section of the longitudinal bore or chamber 364 is greater at the rearward end 366 than at for the forward end 370, and the width of the glide member 374 may therefore be smaller than the glide member 74 of the
In a current embodiment suited for implantation of a donor cornea implant of diameter 9 mm, this may be double coiled and pulled through a minimum bore diameter of 2.57 mm at the forward end 370 without endothelial touch or overlap in embodiments with a ridge or protrusion 382. In embodiments without a ridge or protrusion 382, the implant may be coiled through a minimum bore diameter of 2.9 mm at the forward end 370 without endothelial touch or overlap. As such, the minimum bore diameter in certain embodiments may be in the region of 2.60 to 3.00 mm. Accounting for the thickness of the sidewall, the tubular body 362 may be tapered such that the width of the forward end 370 is approximately 2.7 to 3.0 mm, while the width of the rearward end 366 is approximately 3.5 to 4.0 mm.
In addition, one or more generally parallel ridges, ribs or grooves 305 are provided on the outer surface of the tubular body 362 so as to help resist against extrusion of the cartridge 316 from the anterior chamber of an eye when inserted therein through an incision as shown, for example, in
| Number | Date | Country | Kind |
|---|---|---|---|
| 1103384.2 | Feb 2011 | GB | national |
This application is a continuation-in-part of copending U.S. application Ser. No. 12/657,943, filed Jan. 28, 2010 and published Aug. 19, 2010 under Publication No. US 2010/0211051, which is in turn a continuation-in-part of International Application No. PCT/GB2008/050943, filed 16 Oct. 2008 and published under International Publication No. WO 2009/050511, and which in turn claims the benefit of United States Provisional Application No. 60/980,292, filed Oct. 16, 2007. This application also claims priority from UK Patent Application No. GB1103384.2, filed 28 Feb. 2011. The entire specifications of the foregoing applications are incorporated hereinto by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12657943 | Jan 2010 | US |
| Child | 13374292 | US | |
| Parent | PCT/GB2008/050943 | Oct 2008 | US |
| Child | 12657943 | US |
