Titanium Back Plate for the PMMA Keratoprosthesis – Clinical Outcomes

1. Titanium Back Plate for the PMMA Keratoprosthesis – Clinical Outcomes Claes H Dohlman, Amit Todani, Jared D Ament, James Chodosh, Joseph B Ciolino, Kathryn A Colby, Roberto Pineda, Michael W Belin, James V Aquavella, John M Graney The Boston Keratoprosthesis is manufactured under the auspices of the Massachusetts Eye and Ear Infirmary. Dr. Dohlman, Dr. Chodosh, Dr. Colby, and Dr. Pineda are full-time employees of this hospital. Mr. Graney is the machinist. (J.G.Machine Shop, Woburn, MA)

2. Introduction Up until recently, the Boston Keratoprosthesis (BKPro) has been manufactured exclusively of medical grade poly (methylmethacrylate) (PMMA). This material was introduced to the budding field of keratoprosthesis already some sixty years ago and results have been satisfactory with out overt toxicity. 1-4 The BKPro is shaped like a collar button, modified from previous designs.4-5 In the constant search for improvements, it can be questioned whether other materials than PMMA might be superior. The stem of the device must obviously still be made from a transparent material and likewise the front plate, to allow for inspection of the central carrier cornea. The back plate, on the other hand, which presents a large surface area facing the anterior chamber, does not have to be transparent. Here, among several possibilities, titanium comes to mind considering its widespread successful use in joint replacement, tooth transplants, pacemakers, etc. Titanium has a proven high tissue tolerance and it can be easily machined to thin, flexible plates with still extraordinary strength. Titanium is not new to the keratoprosthesis field. Thus Russian surgeons have used a titanium plate for instrastromal positioning in patients.6 Also, in a more recent rabbit study from Finland, instrastromal haptics of the same material was employed.7

3. In-vitro tolerance Is titanium more “tissue friendly” than PMMA in vitro? A recent study by JD Ament, S Spurr-Michaud, CH Dohlman, and I Gipson has sought to answer that question.8 It was shown in tissue culture using a corneal epithelial cell line that growth over PMMA occurred much slower than over titanium even though neither material caused any distant toxicity in the culture medium (see following graph). MTT Assay: HCLE Cell Growth with PMMA vs. Titanium Tissue culture: growth of corneal epithelial cells over PMMA (bottom curve) and titanium (middle curve) (top curve control). Cells grow better on titanium than on PMMA.

4. Clinical Impression The Boston keratoprosthesis with titanium back plate was introduced at the Massachusetts Eye and Ear Infirmary, Boston , in 2005. Since then a total of 145 such devices have been implanted. The titanium back plate has not yet been approved by FDA for general distribution. The overall clinical impression has been favorable. It has been the unanimous opinion of all collaborators that titanium seems to cause less postoperative reaction than PMMA. Only three devices had to be replaced – in autoimmune patients. A measure of the degree of postoperative inflammation is the formation of a retroprosthesis membrane (RPM). If it becomes sufficiently dense, vision becomes impaired and the membrane will have to be opened with YAG laser, rarely surgically. Here titanium and PMMA back plates have been compared by their rate of triggering a retroprosthesis membrane. It is clear that the use of a titanium back plate results in a statistically significant reduction of RPM formation compared to a PMMA back plate, indicating less postoperative inflammatory reaction (Todani, et al, unpublished data) (see table below).

5. Retroprosthesis membrane formation with PMMA or Titanium back plate at 6 month follow-up Disease CategoryTotal casesTotal no. of RPM Group 1: Threaded PMMA Autoimmune 6 2 (33.3%) Chemical Burns 8 5 (62.5%) Others 25 11 (44.0%) Overall3918 (46.1%) Group 2: Threadless PMMA Autoimmune 3 2 (66.6%) Chemical Burns 2 1 (50.0%) Others 11 2 (18.1%) Overall165 (31.2%) Group 3: Threadless Titanium Autoimmune 3 1 (33.3%) Chemical Burns 1 1 (100%) Others 19 1 (05.2%) Overall233 (13.0%) GRAND TOTAL7826 (33.3%)

6. A: Titanium back plate B: PMMA back plate C: Assembled BKPro with titanium back plate (corneal graft not included)The titanium back plate can be made much thinner than the PMMA: 0.25 mm edge thickness for titanium vs. 0.9 mm for PMMA

7. Pre- and post-operative (3 years) appearance after Boston Keratoprosthesis with titanium back plate.The only disadvantage inherent in the use of titanium may be cosmetic – it can result in a certain metallic sheen. Heavy sandblasting during the manufacturing can diminish this impression, however. Also, tinting or painting of the soft contact lens that must be present anyway, can restore a more natural look. There have been no patient complaints over the appearance of the titanium.

8. Conclusion Boston Keratoprosthesis back plates made of titanium are more “tissue friendly” than those made of PMMA (Ament, et al). Clinically, by gross observation, titanium appears to cause less postoperative reaction. The incidence of retroprosthesis membrane formation is less with titanium than with PMMA back plates (Todani, et al).

9. Bibliography • Wünsche G. Versuche zur totalen Keratoplastik und zur Cornea arteficialis. Ärtzliche Forschung 1947;1:345-348. • Stone Jr. W, Herbert E. Experimental study of plastic material as replacement for the cornea. Am J Ophthalmol 1953;36:168-173. • Dorzee MJ. Kératoprothèse en acrylique. Bull Soc Belg Ophtalmol 1955;108:582-592. • Cardona H. Keratoprosthesis: acrylic optical cylinder with supporting intralamellar plate. Am J Ophthalmol 1962;54:284-294. • Barraquer J. Keratoplasty and keratoprosthesis. Ann R Coll Surg Engl 1967;40:71-81. • Moroz ZI. Artificial cornea. In Fyodorov SN, ed. Microsurgery of the eye: main aspects. Moscow, MIR; 1987. • Linnola RJ, Happonen RP, Andersson OH, Vedel E, Yli-Urpa AU, Krause U, Laatikainen L. Titanium and bioactive glass-ceramic coated titanium as materials for keratoprosthesis. Exp Eye Res 1996;63:471-478. • Ament JD, Spurr-Michaud S, Dohlman CH, Gipson IK. The Boston Keratoprosthesis: comparing corneal cell compatibility with titanium and PMMA. Cornea 2009 Aug;28(7):808-811.