KERATOPROSTHESIS WITH A PLASTIC FIBER MESHWORK SUPPORTING PLATE

REPORT OF AN EXPERIMENTAL AND COMPARATIVE HISTOLOGIC STUDY

HERNANDO CARDONA, M.D. New York

The densely vascularized, granular cornea responds poorly to almost any type of re-parative surgery, especially if it results from a chemical burn (lye). In prosthokera-toplasty, the situation is not much better since this operation has a high extrusion rate due to corneal erosion around the im­plant. When this occurs, additional opera­tions are required in an effort to save the prosthesis but its ultimate extrusion is often inevitable. However, long-term retention of the acrylic keratoprosthesis has been ob­served in eyes with a good collagen fiber framework.1'2

Clinical observations have demonstrated that extrusion of the prosthesis is the result of thinning and erosion of the corneal stro-ma above and around the implant. Since this seemed to be caused by poor nutrition and dehydration of the cornea, an earlier at­tempt was made to correct this situation by reducing the size and amount of plastic ma­terial of the supporting plate.3 So far, this has failed to improve the retention rate of implants in devitalized corneas. Therefore, a search was made for a material that would allow free diffusion of fluids across these corneas and, at the same time, serve as an effective support for the implant. This paper reports the experimental observations and histologic results of tissue tolerance to several synthetic fibers.

MATERIAL AND METHODS

Seven synthetic fibers of the type used as suturing material in vascular surgery were

From the Corneal Center, Department of Oph­thalmology, College of Physicians and Surgeons. This study was supported in part by grant No. NB-04968-03 from the National Institutes of Health, Bethesda, Maryland, and by a Fight for Sight grant-in-aid from the National Council to Combat Blindness, New York.

tested: Dacron (DuPont), Teflon (Du-Pont), siliconized Teflon (DuPont), Silastic (Dow Corning), fiber glass, nylon and cellu­lose. The basic design of the keratoprosthe­sis was the same for each fiber with an ante­rior projection of pure methyl methacrylate 2.0 mm in diameter and a posterior projec­tion of the same pure plastic material, also 2.0 mm in diameter (fig. 1-A and B) . The interlamellar supporting plate, of a fiber meshwork, measured 5.5 mm in diameter and was 0.15-mm thick (fig. 1-C). The walls of the optical cylinder contained a thin layer of pigment to reduce light reflection. This was held in place by a thin layer of pure methyl methacrylate, as shown in Fig­ure 1-D and P.

Seventy albino rabbits weighing about 3.5 kg each were used; 10 for each fiber tested. The test animals were killed at regular in­tervals beginning one month after insertion or upon extrusion of the keratoprosthesis. The eye was then enucleated and prepared for histologic study. Some rabbits from each group were maintained for microscopic study of the eye until extrusion of the im­plant or what was deemed sufficient time to determine that retention would probably be permanent in view of the good tolerance. A few animals are still under observation one year after implantation with no tendency to extrusion of the keratoprosthesis.

SURGICAL TECHNIQUE

General anesthesia was induced with sodi­um pentothal supplemented with ether. A 5.0-mm paracentral incision was made through the anterior two thirds of the cor­neal layers and an interlamellar pocket dis­sected. A 2.0-mm trephine, especially de­signed for this purpose, was used to perfo­rate the corneas centrally. The keratopros-

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thesis was introduced into this interlamellar pocket with the optical cylinder engaging the trephine perforations. The incision was closed with 8-0 silk sutures.

RESULTS

Dacron. Best results were obtained with the Dacron interlamellar supporting plate. Vascularization was minimal (fig. 2-A and B). The corneal tissue over the meshwork plate remained clear. None of the kerato-prostheses in this series of test animals ex­truded. Some of these eyes have now been under observation for one year and the cor­neal tissue over the implant is still transpar­ent (fig. 2-B).

Teflon. Tolerance to the Teflon mesh­work plate was good but, as a result of oxi­dation and macroscopically visible hydra-tion, the fiber showed signs of degradation, readily discernible through the transparent corneal tissue (fig. 2-C and D) . Some of these rabbits have been under postoperative observation for 11 months with no extru­sions of the implant. The progressive degra­dation of the inferior surface of the interla­mellar supporting plate is shown in Figure 2-D.

Siliconized Teflon. In view of the degra­dation and loss of tensile strength observed in the Teflon meshwork supporting plates, the test was repeated in 10 additional rab­bits, using siliconized Teflon. Results with this fiber when it was siliconized were as good as those obtained with Dacron (fig. 2-A and B) and even better.

Silastic. This material was perforated to form a meshwork from which the interla­mellar supporting plates were then fash­ioned. Tolerance and tissue reaction were similar to those observed with Dacron. Some of these eyes have been under obser­vation for 11 months with no extrusions of the implant. However, the material is soft and requires excessive handling during in­sertion of the keratoprosthesis, which natu­rally complicates the surgical procedure.

Fiber glass. The eyes with a supporting plate of fiber glass developed pronounced corneal vascularization with subsequent ul­cération and opacincation during the third postoperative week. Extrusion of the im­plants followed.

Nylon. Tolerance in this series of eyes was good for the first three postoperative months, after which the corneas vascular-

Fig. 1 (Cardona). Cross-section of Cardona through-and-through keratoprosthesis with meshwork sup­porting plate, showing dimensions in mm. (A) Anterior projection of the optical cylinder. (B) Posterior projection of the optical cylinder. (C) Synthetic fiber meshwork supporting plate. (D) Narrow ring of solid plastic fiber to prevent leakage. (P) Pigment.

230 AMERICAN JOURNAL OF OPHTHALMOLOGY AUGUST, 1967

Fig. 2 (Cardona). Photographs of rabbit eyes comparing the reaction to siliconized and nonsiliconized Teflon. (A and B) Keratoprosthesis with siliconized Teflon meshwork supporting plate. Results at 11 months. The fiber retains its structure and pattern with practically no reaction. The eye appears quiet (C) Supporting plate of nonsiliconized Teflon. Some blood vessels are visible, entering from the periphery toward the center of the cornea four months after the operation. (D) The same rabbit at 11 months. The blood vessels have disappeared. There is no visible reaction and the prosthesis appears to be well tolerated but the fiber has deteriorated.

ized, followed by opacification. Three of the 10 keratoprostheses had extruded by the end of the third postoperative month.

Cellulose. There was some reaction in these eyes, with corneal vascularization, ul­cération and opacification over the kerato­prosthesis at the end of the third postopera­tive month. Five of the 10 implants had ex­truded by the end of the seventh month.

HISTOLOGY

Siliconized Teflon. Gross appearance. Three months after the operation the colla­gen fibers maintained their normal structure with no discernible tissue reaction. No blood vessels were evident nor was there any opacification of the stroma (fig. 2-A). At 11 months only one blood vessel was visible, invading the cornea from the periphery (fig.

2-B) but there was still practically no tissue reaction.

Microscopic appearance. The meshwork pattern of this fiber could not be visualized in histologie sections of eyes from rabbits killed at 10 months. Tolerance to the fiber was even more pronounced. This fact was deemed of particular importance in the se­lection of the material to be used to fashion the meshwork supporting plate of the kera­toprostheses for the clinical trial. The epi­thelium was intact. The synthetic fiber and a few epithelial cells were visible in the cornea and stroma. There were no giant cells. The plastic fibers could be clearly demonstrated by means of polarized light.

Teflon. Gross appearance. Some blood vessels invaded the cornea from the periph­ery but they disappeared at 10 months to

VOL. 64, NO. 2 KERATOPROSTHESIS 231

one year. The meshwork supporting plate, which at first appeared intact after observa­tion periods ranging from eight to 12 months, began to lose its architectural struc­ture and the pattern deteriorated as the re­sult of oxidation and hydration (fig. 2-C).

Microscopic examination revealed degra­dation of the fiber, which appeared powder­like between the corneal layers where it was well tolerated. This degradation was easily overcome by siliconizing the Teflon fiber (fig. 2 -AandB) .

Nylon. Gross appearance. A pronounced foreign-body reaction was readily visible macroscopically from the third month.

Microscopic examination revealed marked infiltration of polynuclear leukocytes, lym­

phocytes and eosinophiles. A large number of epithelial cells were visible throughout.

DISCUSSION

Retention of the keratoprosthesis depends upon various factors. In our clinical trial,1·2'4 we first noted that the keratopros­thesis is well tolerated when there is a good collagen framework, even if the cornea is opaque, and that retention is precarious when the collagen fibers have been destroyed by a chemical burn or degenerative process.

Other factors affecting retention of the implant may be a normal fluid flow and inad­equate nutrition of the corneal tissues. Re­cent experimental studies5 show that an in-terlamellar water-impermeable membrane

Fig. 3 (Cardona). Rabbit eye with keratoprosthesis with nylon meshwork supporting plate. At three months some blood vessels are seen entering the cornea from the periphery toward the center. Zones of opacification are seen in the lower quadrants over the nylon meshwork, marked with a solid black line. This same section is shown in (B), the histologie section of the cornea which demonstrates a pronounced foreign-body reaction, infiltration of polymorphonuclear leukocytes (C), lymphocytes, eosinophiles and a large number of epithelial cells throughout. (Hematoxylin-eosin X90).

232 AMERICAN JOURNAL OF OPHTHALMOLOGY AUGUST, 1967

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Fig. 4 (Cardona). (A) Rabbit eye with keratoprosthesis with siliconized Teflon meshwork supporting plates 10 months after insertion. There is practically no reaction in the upper half, marked with a solid black line over the meshwork, which corresponds to the histologie section (B), which shows perfect toler­ance to the fiber. There is no infiltration of the surrounding stroma. The collagen fibers, epithelium and endothelium are practically intact. (Hematoxylin-eosin χ60).

inhibits the passage of fluids across the cor­nea, which could diminish the nutrition of the tissue anterior to the membrane, while a physiologic study of tears and the effect of interlamellar membranes on the movement of corneal fluid demonstrated that the evap­oration of water from the corneal surface and subsequent changes in the composition of the tears enhance dehydration of the an­terior layers.8-7 This excessive dehydration in turn leads to degeneration of the corneal tissue, as would inadequate nutrition.

When a solid plastic plate is used to sup­port the optical cylinder of the keratopros­thesis, erosion of the host corneal tissue is frequently observed around the lower half of the optical cylinder and rarely around the upper half where the lid affords protection, maintaining the tissues moist or wet.8-8 This definite pattern of erosion may be explained by the fluid flow just described. Thus, it

seemed desirable to support the optical cyl­inder of the prosthesis with a structure that would permit the fluid and nutritional sub­stances to diffuse to the anterior layer of the cornea. Stone10 advocates perforation of the interlamellar supporting plate.

In view of these considerations, a kerato­prosthesis was designed with an improved system to support the optical cylinder and to serve the following purposes: (1) permit the free passage of fluids, (2) provide flexi­bility allowing adaptation to the corneal cur­vature and (3) assume the role of the dam­aged or destroyed collagen fibers.

The results of these experiments justified the continuation of clinical trials begun in 1962, using the keratoprosthesis with a meshwork supporting plate of siliconized Teflon. This material is now being used in unfavorable human eyes of the type in which extrusion of the original implant has

VOL. 64, NO. 2 KERATOPROSTHESIS 233

been a major complication; that is, in eyes that have suffered a severe chemical (espe­cially lye) burn in which the collagen fibers are no longer intact and the cornea is granu­lar and densely vascularized.

Results of the clinical observations will not be reported for at least two years, until a sufficient number of cases have been ac­cumulated and kept under observation for enough time to reach definitive conclusions regarding the usefulness of this new kerato-prosthesis.

SUMMARY

The major complication of prosthokerato-plasty continues to be a tendency to extru­sion of the implant. The possible causes of extrusion are discussed and an experimental study of the use of a keratoprosthesis with a meshwork plastic plate to support the opti­cal cylinder is reported. The results ob­tained with siliconized Teflon were sufficient­ly encouraging to justify a clinical trial which is now under way.

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REFERENCES 1. Cardona, H., Castroviejo, R. and DeVoe, A.

G. : The Cardona keratoprosthesis : First clinical evaluation. Acta. XIX Counc. Ophth. 2:1211, 1962.

2. : Techniques of prosthokeratoplasty : Evaluation of results with the Cardona kerato­prosthesis. Presented at the XX Intern. Cong. Ophth. Munich, 1966.

3. Cardona, H. : Keratoprosthesis : Acrylic opti­cal cylinder with supporting intralamellar plate. Am. J. Ophth. 54:284, 1962.

4. : The Cardona keratoprosthesis: A suspended through-and-through model. Presented at the XX Intern. Cong. Ophth. Munich, 1966.

5. Knowles, W. F. : Effect of intralamellar plastic membranes on corneal physiology. Am. J. Ophth. 51:1146, 1961.

6. Brown, S. I. and Mishima, S. : Effect of in­tralamellar membrane on the hydration of the cornea. Arch. Ophth. in press.

7. Mishima, S. : Some physiological aspects of the precorneal tear film. Arch. Ophth. 73:233, 196S.

8. Brown, S. I. and Dohlman, C. H. : A buried corneal implant serving as a barrier to fluid. Arch. Ophth. 73:635, 1965.

9. Cardona, H. : Plastic keratoprostheses : A description of the plastic material and compara­tive histologie study of recipient cornea. Am. J. Ophth. 58:247, 1964.

10. Stone, Jr., W. : Alloplasty in surgery of the eye. New Eng. J. Med. 258:486, 533, 596, 1958.

EFFECT O F AZATHIOPRINE (IMURAN) ON CORNEAL GRAFT REACTION

FRANK M. POLACK, M.D. New York

I. MODIFICATION OF THE CORNEAL GRAFT REACTION BY SUBCONJUNCTIVAL

AZATHIOPRINE

Corneal graft opacification can occur as a result of an immunoallergic reaction similar to that caused by tissue transplants else­where in the body. As in these cases, the

From the Corneal Center, Institute of Ophthal­mology, College of Physicians and Surgeons, Co­lumbia University. This study was supported by grant No. NB-04968-03 from the National Insti­tutes of Health, Bethesda, Maryland. Portions of Part I were presented at the symposium on pre­vention of graft rejection with emphasis on the cornea, Little Rock, Arkansas, December, 1965. Part III was presented in part at the midwinter meeting of the Eastern Section of the Associa­tion for Research in Ophthalmology, Philadel­phia, April 1, 1966.

graft reaction is systemic in nature but the form in which antigens are presented to lymphocytes and the site of interaction is still unknown.1

One method of inhibiting the host reac­tion to a tissue graft is by means of immu-nosuppressive drugs, such as 6-mercapto-pu-rine or azathioprine, which, unfortunately, carry with them a great deal of toxicity, par­ticularly on long-term treatment.2-3 They also have the inconvenience that effective thera­peutic dosages are very close to toxic levels.* In previous reports, it has been shown that systemically administered azathioprine can effectively suppress the rejection of penetrat­ing experimental corneal homografts8·5-6 and heterografts7'8 but, since toxic effects and