Plastic Keratoprostheses*

DIURNAL TENSION VARIATION

247

REFERENCES 1. Maslenikow, Α . : Ueber Tagesschwankungen des intrakularen Druckes hei Glaukom. Augenh., 1 1 : 564, 1904. 2. Drance, S. M . : Diurnal variation of intraocular pressure in treated glaucoma. A M A Arch. Ophth., 70:302, 1963. 3. Duke-Elder, S.: The phasic variations in the ocular tension in primary glaucoma. Am. J. Ophth., 35:1, 1952. 4. de Roetth, A . : Effect of changes in osmotic pressure of blood on aqueous humor dynamics. A M . \ Arch. Ophth., 52:571, 1954. 5. Leydhecker, W . : The water drinking test. Brit. J. Ophth., 34:457, 1950. 6. Galin, M. Α., Aizawa, P., McLean, J. M . : The water provocative test in glaucomatous patients. Am. J. Ophth., 52:15, 1961. 7. Sugar, H . S.: The Glaucomas. New York, Hoeber, 1957, pp. 179-180. 8. Drance, S. M . : Studies with applanation water tests. A M A Arch. Ophth., 69 :39, 1963. 9. de Venecia, G., David, M. D . : Diurnal variation of intraocular pressure in the normal eye. A M A Arch. Ophth., 69 :753, 1963. 10. Drance, S. M . : The significance of diurnal tension variations in normal and glaucomatous eves. A M A Arch. Ophth., 64:497, 1963. 11. Friedenwald, J. S.: Editorial: Committee on Standardization of Tonometers. Tr. Am. Acad. Ophth., Jan.-Feb., 1949, pp. 261-262. 12. Galin, M. Α . : Effect of water provocative test on ocular rigidity. A M A Arch. Ophth., 70:337, 1963.

PLASTIC

KERATOPROSTHESES*

A DESCRIPTION OF THE PLASTIC MATERIAL AND COMPARATIVE HISTOLOGIC STUDY OF RECIPIENT CORNEAS HERNANDO CARDONA, M . D . Neiv York

The purpose o f this study was to design a

Innately, it was possible to eliminate the un-

useful and satisfactory keratoprosthesis c o m -

desirable substances used in industry and to

bining all the features o f an intraocular for-

obtain the desired degree o f hardness

eign body that would not, however, cause

transparency.

undesirable

reactions in the live recipient

ocular tissues. T o accomplish this two steps

these experiments are summarized T h e basic acrylic resin formula is:

1. T o find the cause o f the continual e x ­ o f the plastic implants

in this

communication.

were necessary: trusion

and

T h e encouraging results o f

R

heretofore

used.'-"

CH2=C'

2. T o find the degree o f reaction of the

\

corneal tissues to different plastic materials.

T o this end, some 160 different varieties

COO(R)

^

characterized chemically b y a type o f

of acrylic resins, structurally different but

monomer

similar in appearance, were studied. F o r -

molecular changes. T h e commercial processes

* From the Department of Ophthalmology, College of Physicians and Surgeons Columbia University This investigation was made possible by a grant from the Corneal Research Fund of the Institute of Ophthalmology, Columbia-Presbyterian Medical

ST'Nat^l^^SS^'^^^bi^Hn^^^ New York.

vinyl

capable

of

innumerable

used in the production o f the more common monomers, the majority o f which are based acetone-cyanhydric process, have •' •' ' ' demonstrated h o w many acrylic acids can be synthesized. T h e subsequent reaction with

-'ί"- d ^PP''-^'- °f P™duces a crude molecule o f methacrylamide

HERNANDO CARDONA

248

sulfate. This can be synthesized by the re­

of the plate. Fabrication and sterilization o f

action o f ethylene oxide with hydrogen cya­

the plastic was the same for all the kerato­

nide. Unfortunately, these synthesizing proc­

prostheses.

esses re(|uire great

(|uantities o f cyanides

The following techiii
and the final product is highly inflaminable,

plantation:

potenfially exi)losi\'c and, in some forms, it

was made through

contains

of the cornea where an interlamellar pocket

free

radicals

of

non-neutralized

A

five-mm.

acid. Acrylonitrile is extremely toxic and

was dissected. A

may even be absorbed by the skin.«

made with a trephine

Many

polymerizations

are

effected

by

and

the

paracentral incision

the anterior two thirds central

prosthesis

perforation

was

1.5 mm. in diameter

was

implanted

in

the

using free radicals as the catalyst. These in­

pocket with the cylinder filling the trephined

clude benzol peroxide and other substances

perforations. T h e incision was closed with

that are added to the mixture during poly­

7-0 silk sutures.

merization to insure "thermo-setting" o f the

Albino rabbits weighing five to six pounds

polymer. Mercaptans are generally used to

were selected for the study. Anesthesia was

lower

general, sodium pentothal supplemented with

the molecular weight and

obtain a

lighter plastic. Hydroquinone is used as an

ether.

inhibitor. It should be removed before the

T h e rabbits were divided into t w o groups:

polymerization process is started as all these

(1)

substances are highly toxic. T h e p H o f the

commercially available plastic material; and

10 were used to test implants made of

final product should be neutral. N o inhibitors

( 2 ) 10 to test implants made of plastic ma­

were used. T h e mixture was adjusted to a

terial polymerized according to our method.

neutral p H . RESULTS

Actually this polymerization process is the least practical from a commercial point o f view

because

Starting with

it

is very time-consuming.

a monomer, methyl

GROUP I (commercial plastic) First three days:

metha-

Slight

corneoconjunc-

crylate, ultraviolet light was used to effect

tival injection. N o signs o f aqueous humor

the polymerization in this study. T h e final

filtration

through the corneal incision.

plastic material thus obtained was then tested

Fourth day: Slight edema and opacifica­

in rabbit corneas for six months before it

tion o f the cornea and a congested and hy-

was inserted in human eyes.

peremic iris were noted. Sixth to

MATERIALS AND ΛΙΕΤΗΟΟ

opacification.

T w o different methyl methacrylates were

10th day:

Increase

Abundant

mucous

in corneal secretion

noted.

( 1 ) Plexiglass, o b ­

Twelfth day: Cornea too opaque to per­

tained from a commercial supplier (Glasflex,

mit visualization o f details o f the anterior

Inc., Stirling,

chamber. There was an increase in mucous

used as basic material:

N e w J e r s e y ) , and

( 2 ) one

polymerized according to my method. Identi­

secretion, marked

cal keratoprostheses, consisting of an optical

of

cylinder 1.25-mm. long with an anterior di­

plant; conjunctival and palpebral edema.

ameter of 1.50 mm. and a posterior one of 1.60

mm., were

made

of

each

material.

These were anchored in the recipient corneas

reaction and

the corneal tissue

thickening

surrounding the im­

All the implants were extruded between the 17th and 28th day after

insertion and

the eyes were then enucleated. T h e histologic

by a plate made of the same plastic material.

study was essentially the same in each case.

T h e plate was 3.5 mm. in diameter and 0.15-

T h e keratoprosthesis was retained in three

mm. thick. T h e ends of the cylinder pro­

sections. T h e plastic material was softened to

truded 0.40 mm. both in front and in back

permit cutting without damaging the knife.

PLASTIC KERATOPROSTHESES

249

Fig. 1 (Cardona). Section of the cornea adjacent to a keratoprosthesis of commercial plastic on the 4Sth postoperative day, showing marked reaction of the corneal tissue. ( A ) Epithelium thinned and end­ ing in a fine thread of basal cells. The rest of the area has no epithelium. ( B ) Area of necrotic tissue circumscribed by purulent exudates. ( C ) Numerous vessels in the corneal tissue substance. ( D ) Intralamellar spaces in the corneal tissue invaded by polymorphonuclear leukoc\'tes. ( E ) Endothelium torn by the plastic. It is also infiltrated by polymorphonuclear cells.

HISTOLOGIC STUDY

This was accomplished by means o f a depolymerization process.

GROUP I

GROUP II (plastic polymerized in this labo­ ratory)

Gross appearance (fig. 1). T h e normal architecture and structure of the cornea has been partially destroyed by the inflamma­ tion. The tissue in contact with the implant has increased to three times its normal thick­ ness in the form o f a "mushroom." A cir­ cumscribed zone of necrotic tissue is visible at the apex (fig. 1 - B ) .

First three days: Slight corneoconjunctival reaction present. N o filtration o f aque­ ous humor through the corneal incision. Fourth day: N o obvious changes. Sixth to 10th day: Cornea clear with slight vascularization bordering the sutures. Eleventh to 15th day: The three sutures extruded spontaneously. Four o f the 10 rabbits were killed dur­ ing the early days o f the trial. T h e implant was retained for a period o f nine to 14 months in the corneas o f the remaining six rabbits.

T h e limbal conjunctiva was infiltrated with lymphocytes, the vessels congested and the corneal epithelium surrounding the elevated " m u s h r o o m " finely thinned and covered with organized inflammatory tissue. There was pronounced polymorphonuclear leukocyte in­ filtration and dense vascularization. Intra-

250

HERNANDO CARDONA

change in the corneal epithelium. Figure 1-B shows division o f the basal and polygonal cells growing to cover the stroma o f the cut surface. A t first it appeared that this epi­ thelial proliferation would continue into the anterior chamber. A comparison with the section o f a cornea and prosthesis at 14 months after operation (fig. 3 ) proved this to be an erroneous supposition. T h e cornea, conjunctiva and iris were normal, as was the depth o f the anterior chamber. Figure 3-B and C shows the most impor­ tant effect, which was noted in the epithe­ lium. It had proliferated and completely

Fig. 2 (Cardona). Section of a cornea adjacent to a keratoprosthesis on the fourth postoperative day. The section shows the absence of corneal tissue reaction to an implant made of plastic polymerized in the laboratory. ( A ) Anterior appendage of the optical cylinder of the prosthesis. ( B ) The epithe­ lium proliferates at the border of the trephined stroma. ( C ) Normal corneal stroma.

lamellar spaces with polymorphonuclear leukocyte infiltration were visible and poly­ morphonuclear cells could be seen in the en­ dothelium. T h e anterior chamber contained fibrinopurulent exudates. GROUP I I

Gross appearance (fig. 2) four days after operation. T h e corneal structure is retained and the corneal tissue in contact with the implant is clear. T h e eye showed the cus­ tomary postsurgical reaction. Depth o f the anterior chamber was normal. There was no iris congestion. T h e conjunctiva was normal. T h e outstanding feature noted was the

Fig. 3 (Cardona). Section of a cornea and ad­ jacent keratoprosthesis obtained 14 months post­ operatively, showing lack of reaction by the corneal tissue to the plastic which was polymerized in the laboratory. ( A ) Anterior appendage of the optical cylinder. ( B ) . Epithelium proliferated to cover completely the stromal border touching the implant. The basal cells end in a fine thread ( C ) .

251

PLASTIC KERATOPROSTHESES

covered the trephined corneostromal surface. Gradual thinning o f the basal cells, which end in a fine wirelike structure, is evident where the cylinder joins the

intralamellar

plate (fig. 3 - C ) . Proliferation ceased at this point.

Other

sections

showed

the

same

phenomenon, thus indicating that epithelization o f the anterior chamber was highly im­ probable. STUDY OF THE ENDOTHELIUM T h e fate o f the endothelium was studied using: ( 1 ) the front view of a short proto­ type with posterior surface at the same level (fig. 4 - B ) ; and ( 2 ) the front view o f a large

Fig. 5 (Cardona). Result of extending the pos­ terior appendage into the anterior chamber to pre­ vent the endothelium from covering the posterior surface of the implant. ( A ) Posterior appendage of the implant. ( B ) Iris free from the posterior surface of the implant. ( C ) Anterior lens surface.

keratoprosthesis with the posterior append­ age inside the anterior chamber (fig. 5 - A ) . Another series o f albino rabbits

o f the

same weight as those used in the previous trial were used to study the behavior o f a prosthesis in which the optical cylinder e x ­ tended just to or beyond the surface o f the endothelium. T h e same surgical

technique

was used for its insertion. A l l the test ani­ Fig. 4 (Cardona). Section of a cornea containing a prosthesis in which the posterior surface and the endothelium are at the same level. The endothelium proliferated, covering the posterior surface of the implant and thereby interfering with the optical property of the implant. ( A ) Posterior appendage of the implant. ( B ) Endothelium.

mals were killed six months after the o p ­ eration since it was felt this would allow the epithelium ample time to proliferate over the posterior surface o f the optical cylinder o f the keratoprosthesis if it were going to d o so.

252

HERNANDO CARDONA

A keratoprosthesis with the posterior sur-

posterior surface of the implant completely

face very nearly even with the endothelium

free, permitting the passage o f light. This

was placed in five rabbit corneas (fig. 4 ) ,

phenomenon is clearly illustrated in Figure

while a second type o f keratoprosthesis in

5. T h e posterior surface of the keratopros­

which the posterior surface extended 1.50

thesis faces the pupillary border and the an­

mm. below the endothelium was placed in

terior

the remaining five rabbit corneas.

tendency o f the iris to form synechiae. T h e

surface o f the lens. There was no

Results of this study showed that, when

posterior surface o f the implant was coated

the surface of the keratoprosthesis and the

by an extremely fine film, the result o f a phys­

endothelium were at the same level, the latter

iologic process o f cell formation that coats

proliferated and covered the posterior sur­

any substance inside the anterior chamber.

face o f the implant (fig. 4 ) . This result has

Possibly these cells aid in or effect the meta­

been

bolic interchange in the cornea and they may

reported

by

other

investigators.^'* his

float freely in the aqueous humor. T h e y are

studies, the posterior hole remained patent

transparent and can be visualized only by

even though the plastic and hole were at the

staining procedures.

Stone,^'"*

however,

reports

that,

in

same level. He replaced the aqueous humor with a two-percent solution o f sodium citrate preoperatively. This prevented the precipita­ tion of a fibrin matrix in the opening. H e was o f the opinion that the endothelial cells require this fibrin scaffolding to grow across the

opening and

showed photographs o f

openings that had remained patent for as long as 29 months to the natural death o f the animal. T o avoid this complication I lengthened the posterior portion of the cylinder in the anterior chamber. T h e endothelium did not proliferate over the cyhnder to form a type o f cellular condensation over it. This left the

SUMMARY Experiments

are

reported

that

clearly

demonstrate that the plastic material used to make a keratoprosthesis must be carefully polymerized without using any organic cata­ lysts or inhibitors. T h e material, destined for use in human eyes, was tested in rabbit eyes for a period of at least six months before it was implanted in the recipient cornea. A n y plastic

material

that

caused

the

slightest

corneal reaction in the test animal was dis­ carded. 630 IVest 168th Street

(32).

REFERENCES 1. De Rezende, Cvro: El implante corneano de acrilico, contribución experimental. An. Inst. Barraquer, 5-6 :821-839, 1963. 2. Cardona, Η . : Keratoprosthesis: Acr3 lie optical cj'linder with supporting intralamellar plate. Am. T. Ophth., 54:284-294 (Aug.) 1962. 3. Stone, W . , Ir.: AUoplasty in surgery of the eye. New Eng. J. Med., 258:486-490, 533-540, 596-602 (Mar. 6, 13& 20), 1958. 4. Stone, W., Jr.: Plastic and cornea: Fourteen years' study. A.M.A. Exhibit, 1963. 5. Barraquer, J.: Inclusion de protesis opticas corneanas, corneas acrillicas o queratoprostesis. An. Inst. Barraquer, 1:243-247, I960. 6. Honi, Milton R.: Acrylic Resins. New York, Reinhold, 1960.