Australian Journal of Ophthalmolopy. (1981). 9, pp, 47-50

CORNEAL DAMAGE AFTER INTRAOCULAR SURGERY

HERBERT E. KAUFMAN, M.D. LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans, Louisiana

Summary The corneal endothelium maintains corneal transparency by providing a fluid barrier between the aqueous humor and the corneal stroma. Loss of funtional integrity af this cell layer results in corneal edema and a reduction in visual acuity. Because the corneal endothelial cells appear not to replicate by cell division. damaged areas heal only by the enlargement and spreading out of the remaining cells. Thus, there is a limit to the “healing reserve” of the endothelium and excessive surgically-induced trauma coupled with natural cell losses due to aging can result in loss of endothelial function and corneal decompensation. Contact between corneal endothelial cells and the intraocular lens during lens insertion causes stripping of the cell membranes and cell death. Prevention of this damage can be obtained through improved surgical techniques and modifications of intraocular lens surfaces. In addition, studies are in progress to find ways to stimulate endothelial cell regeneration.

INTRODUCTION Intraocular surgical procedures, such as intraocular lens insertion, phakoemulsification, and vitrectomy, can be associated with immediate or postponed complications resulting from trauma to the cornea during surgery. Although the corneal epithelial cells are capable of replacing damaged cells in this layer, and the stroma is relatively acellular, the corneal endothelium is susceptible to permanent damage from the most casual contact with hostile materials during intraocular surgery. The result of this damage may not be immediately evident, and the surgical procedure may appear to have been a success. However, post-operative corneal decompensation may occur either shortly after such surgery, or at a somewhat remote time when surgical healing has apparently been complete. Such decompensation may even present

after a period of years, when the related surgical trauma has been all but forgotten.

Only recently has our understanding of corneal physiology improved sufficiently to explain such complications and their relationship to surgical techniques. Even more recently, we have begun to seek ways to prevent these problems through modifications in surgical procedures and materials. These are the topics I shall discuss here.

The Corneal Endothelium The corneal endothelium consists of a single layer of mesodermally-derived cells which provide a “water pump” for the maintenance of corneal deturgescence. This barrier between the aqueous humor and the corneal stroma prevents accumulation of fluid in the stroma and the accompanying corneal cloudiness and reduction in

This work supported in part by US Public Health Service grants EY02580 and EY02377 from the National Eye Insti Ute, the National Institutes of Health, Bethesda. Maryland. Reprint reqirests: Herbert E. Kaufman, M.D. LSU Eye Center, 136 South Roman Street, New Orleans. LA 701 12, USA.

C O R N E A L D A M A G E AFTER INTRAOCULAR SURGERY 47

visual acuity. Thus the maintenance of corneal transparency essential to vision is the primary function of the corneal endothelial cell layer. Loss of endothelial function and the resulting corneal edema can culminate in such common corneal diseases as bullous keratopathy and Fuchs’ dystrophy.

The development of the specular microscope1 2 3

has made possible the direct examination of the corneal endothelial cells in the living eye. Earlier histological preparations had shown larger numbers of endothelial cells in younger donor eyes. and smaller numbers in older donor eyes.4 Observations made with the specular microscope confirmed an apparent decrease in numbers of endothelial cells correlated with increasing age of the donor eye. It was also seen that these endothelial cells do not appear to replicate through cell division. Endothelial repair is achieved by the enlarging and spreading out of the remaining cells to cover the spaces left by the loss of damaged cells.5 Therefore, both induced ocular trauma and natural aging processes lower the number of functional endothelial cells and reduce the “healing reserve” of this cell layer. When these factors combine to decrease the endothelial cell density beyond its ability to heal, functional integrity is lost and trouble begins.

Intrcrociilrrr Lens Siirgery und Corned Endothelid D~nictge We have seen that corneal edema occurs following the implantation of intraocular lenses at a much higher rate than has been reported in conjunction with standard cataract extractions. In examination of our own intraocular lens insertion patients with the specular microscope, we saw the characteristic enlargement of the endothelial cells and the reduced numbers of cells that indicated severe cell damage and loss resulting from the surgical procedure. At that time, intraocular lens insertion entailed leaving the anterior chamber flat for a short time while a running nylon suture was being placed. We had no idea that such temporary contact between the intraocular lens and the corneal endothelium could be harmful, as long as the anterior chamber ultimately was formed.

Further evidence that intraocular lens insertion

48

was accompanied by endothelial cell loss more severe than that associated with cataract extraction‘ prompted us to examine the relationship between endothelium/lens contact and cell damage, particularly in view of findings indicating that neither the type of lens nor the length of lens “wearing” time affected the degree of cell loss. In several in vitro studies using donor eyes obtained from eye banks.’ ’ we found that touching the corneal endothelium with the polymethyl methacrylate lens material for even the briefest time resulted in damaged cells. The cell membranes adhered to the plastic lens, and any removal of the lens, particularly with any lateral movement, stripped the membranes from the cells, exposing the cell contents and ending in cell death, as shown by uptake of nitro blue tetrazolium dye. The amount of contact between the cells and the lens correlated directly with the amount of damage and subsequent cell death.’ In vitro contact between the endothelial cell layer and human or animal natural lens material produced no damage to the endothelial cells.

Preventing Endothelid Dumuge During Intruocitlcrr Lens Sitrgery Our first approach to the prevention of this type of endothelial damage involved modifications in surgical technique which eliminated as much contact as possible between the cells and the inserted lens.’ ’ l o Attempts were made to maintain an air bubble between the lens and the cornea. When successful, this procedure did reduce endothelial cell loss during lens insertion; however, even with extreme care on the part of the surgeon, the rate of success was variable.

A second approach to prevention of cell loss has been to obviate the deleterious effects of lens/cell contact. Various researchers have attempted to cover or coat the intraocular lens with a substance which does not adhere to the cell membranes, thereby rendering such contact harmless to the endothelial cells.

In order to prevent the apparent reaction between the hydophobic lens material and the cells, coating materials which would improve the hydrophilicity of the lens surface were tried. we attempted to prevent lens/cell friction by binding

AUSTRALIAN JOURNAL OF OPHTHALMOLOGY

a layer of water to the lens surface by coating it with hydrophilic substances such as polyvinyl pyrrolidone and methyl cellulose.’ Significantly less endothelial damage was seen using this procedure in vitro.

Others found similar results using normal saline, plasma, tissue culture fluid, albumin and serum. i

Peyman and Zweig used bovine submaxillary mucin type I, and reported endothelial cell loss of 4.3% as compared to 30.9% with uncoated lenses in vitro.” In cat eyes, Levy and coworkersi3 implanted a protective Polymacon lens cut to fit the anterior chamber between the intraocular lens and the corneal endothelium, and found reduced endothelial cell loss. Miller and Stegmann14 filled the anterior chamber with sodium-hyaluronate before implanting intraocular lenses in human eyes, obtaining endothelial cell loss rates similar to those of standard cataract extraction series. The Heyer-Schulte Company has recently tested a polyvinyl alcohol dissolvable . coating for intraocular lenses which has proven successful in animals and is now in the experimental stages of human use.I5 This kind of coating has the advantage of being applicable by the manufacturer, thus reducing the possibility of contamination. During contact with the endothelial cells, a minute portion of the coating layer is deposited on the endothelial cells, and the shearing plane is then located within the coating layer and not at the endothelial cell surface. In addition, this coating is eventually dissolved from the intraocular lens surface and removed from the eye, eliminating the problem of long-term toxicity.

An entirely different approach currently under investigation involves the stimulation of the normally non-dividing endothelial cells to increase their numbers by replication. Fabricant16 and others” have demonstrated receptors for epidermal growth factor on both cat and human corneal endothelial cells. If such a growth factor could be found to successfully stimulate corneal endothelial cell division, damage to this essential cell layer could be repaired in vivo by cell replacement. Imagine the possibility of being able to someday instill some growth factor after surgery and having the endothelium actually heal itself.

InTplicutions of Corneal Endothelial Damage The result of the loss of functional endothelial integrity is corneal edema, which varies in seventy from a transient cloudiness to corneal decompensation. A major reduction in endothelial cell count due to surgically-induced trauma may jeopardize the visual results of otherwise successful intraocular lens implantation. Even minor damage to the endothelial cell layer, while not producing immediately noticeable symptoms, may reduce cell density such that, in later years, combined with the cell losses due to natural ageing processes, there will be insufficient cells to provide an effective fluid barrier, and corneal decompensation will result. Thus the damage to the endothelial layer accompanying the earlier surgery may culminate in the need for later keratoplasty to maintain or restore satisfactory visual acuity.

For example, Spencer and Fine” followed the congenital glaucoma patients Barkan had cured with goniotomy. About 20 years later, many of these patients with stretched corneas developed corneal edema. Maumenee and Stark” cured patients with epithelial downgrowth but found that, one to two years later, the corneas with damaged endothelium decompensated. Even in keratoplasty, the small grafts with poor tissue decompensated after a few years.

Consider also the early history of intraocular lens implantation with crude lenses and no microsurgery. Are we really sure that the late corneal decompensation so often seen was due to poor lens design and continued damage or could it have been delayed decompensation from severe insult to the endothelium at the time of surgery?

One somewhat comforting thought, however, is that, if edema occurs, there is still an excellent chance of restoring satisfactory vision by corneal transplantation. In a recent series,29 we obtained 95% clear grafts with a follow-up of at least one year in every case. Seventy-eight per cent showed a visual acuity of 20/80 or better in this series, excluding only failed grafts, deaths (due to unrelated causes), and cases of macular degeneration. With this level of success in this type of surgery, we can hope to restore acceptable visual acuity for many of these corneal decompensation patients.

CORNEAL DAMAGE AFTER INTRAOCULAR SURGERY 49

References I . Maurice, D. M.: Cellular membrane activity in the

corneal endothelium of the intact eye. Experientia, 1968, 24: 1094.

2. Laing. R. A,. Sandstrom. M. M. and Leibowitz. H. M.: In vivo photomicrooraphy of the corneal endothelium. Arch. Ophthal. 197?, 93: 143.

3. Bourne, W. M. and Kaufman. H. E.: Specular of the human corneal endothelium In vivo.

!$zs?8phthal., 1976. 81:319. 4. Irvine. A. R. and Irvine, A. R.. Jr.: Variations in normal

human corneal endothelium. Amer. J. Ophthal., 1953. 36: 1279.

5. Bourne. W. M. and Kaufman, H. E.: Endothelial damaze associated with intraocular lenses. Amer. J. Ophttial.. 1976. 8 1:482.

6. Forstot. S. L.. Blackwell, W. L.. Ja fe , N. S., and Kaufman, H. E.: The efect of intraocular lens implantation on the corneal endothelium. Trans. Amer. Acad. Ophthal. and Otolar., 1977, 83:0P195.

7. Katz, J., Kaufman. H. E.. Goldberg, E. P., and Sheets, J. W.: Prevention of endothelial damage from intraocular lens insertion. Trans. Amer. Acad. Ophthal. and Otolar., 1977. 83:0P204.

8. Kaufman. H. E.. Katz. J., Valenti, J., Sheets, J. W., and Goldberg. E. P.: Corneal endothelium damage with intraocular lenses: contact adhesion between surgical materials and tissue. Science, 1977, 198:525.

9. Sugar, J., Mitchelson, J. and Kraf , M.: Endothelial trauma and cell loss from intraocular lens insertion. Arch. Ophthal., 1978, 96:449.

10. Bourne. W. M., Brubaker. R. F. and O’Fallon. W. M.: Use of air to decrease endothelial cell loss during intraocular lens implantation. Arch. Ophthal., 1979. 97: 1473.

11. Kirk. S., Burde, R. M. and Waltman. S. R.: Minimizing corneal endothelial damage due to intraocular lens contact. Invest. Ophthalmol. and Vis. Sci., 1977. 16: 1053.

12. Peyman, G. A. and Zweig, K.: Dry coating of intraocular lenses with bovine submaxillary m u c h Amer. J. Ophthal., 1979, 87:561.

13. Levy, P. L., Roth, A. M. and Gangitano, J. L.: Protection of corneal endothelium during intraocular lens implantation using Polymacon, a new surgical technique. Ophthalmology, (in press).

14. Miller. D. and Stegmann, R.: Use of Na-hyaluronate in human IOL implantation. Amer. Intra-Ocular Implant. Soc. J., (in press).

15. Knight, P. M. and Link, W. J.: Surface modification of intraocular lenses to reduce corneal endothelial damage. Amer. Intra-Ocular Implant. SOC. J., 1979. 5: 123.

16. Fabricant, R. N., Alpar, A. J.. Centifanto, Y. M. and Kaufman, H. E.: Epidermal growth factor receptors on feline and human corneal endothelium. In preparation.

17. Gospodarowicz, D., Mescher, A. L. and Birdwell, C. R.. Stimulation of corneal endothelial cell oroliferation in vitro by fibroblast and epidermal growih factors Exp Eye Res , 1917.25 75.

18. Spencer. W. H , Fereuson. W J , Jr, Shaffer. R N and Fine, M.: Late degenerative changes in the cornea following breaks in Descemet’s membrane. Trans. Amer. Acad. Ophthal. and Otolar., 1966, 70:973.

19. Maumenee, A. E. and Stark, W.: in Boyd, B. Highlights of Ophthalmology, Vol. XV, 20th Anniversary Edition. Panama, 1978, pp.35 1-352.

20. Olson, R. J., Waltman, S. R., Mattingly, T. P. and Kaufman, H. E.: Visual results after penetratinz keratoplasty for aphakic bullous keratopathy and Fuchb dystrophy. Amer. J. Ophthal. (In press).

50 AUSTRALIAN JOURNAL OF OPHTHALMOLOGY