TIME ANALYSIS OF CORNEAL ENDOTHELIAL CELL DENSITY AFTER CATARACT EXTRACTION

M I L E S A. G A L I N , M.D., LUKE L O N G L I N , M.D., E D W A R D F E T H E R O L F , M.D., S T E P H E N A. OBSTBAUM, M.D., AND ALAN SUGAR, M.D.

New York, New York

The specular microscope has permitted the study of the effect of surgery on corne-al endothelial cell density.1 A cornea may remain clear after significant cell loss, but perhaps lose function at some future date if a critical number of cells do not re­main.2 Because that critical number is unknown, every possible effort is made to preserve the endothelium at surgery.3

Consequently, a variety of medical and surgical additions have been made partic­ularly for implant surgery to prevent en­dothelial cell loss.4 '5

In order to assess the usefulness of changes in technique, the use of surgical devices, or the addition of coatings to implants, it is essential to know the natu­ral course of cell loss after cataract sur­gery. Various reports present widely dif­fering ranges, not simply explained by technique. Where in the cornea the photo­graphs were taken and at what period after surgery, vary enormously. For exam­ple, Bourne and Kaufman6 report counts from one day to eight weeks, Forstot and associates7 from six to 13 days, and Hirst and associates8 from four to 233 days.

A study was initiated both in cats and cataract patients to assess the nature of central endothelial cell change after rou­tine and implant cataract surgery. The cat

From the Department of Ophthalmology of the New York Medical College, (Drs. Galin, Lin, and Fetherolf), and the Department of Ophthalmology of Mt. Sinai Medical Center, (Drs. Obstbaum and Sugar), New York, New York. This study was sup­ported in part by Grant NOl AI 81266 from the National Institute of Allergy and Infectious Disease, and a grant from the Ophthalmological Foundation of America, Inc.

Reprint requests to Miles A. Galin, M.D., Oph­thalmological Foundation of America, Inc., 113 E. 39th St., New York, New York 10016.

AMERICAN JOURNAL OF OPHTHALMOLOGY

data have already been reported and show that a progressive decrease in central cell density occurs for approximately three months after surgery, at which time it essentially stabilizes.9 We compared im­plant and simple cataract extraction pa­tients and report essentially the same chronologic findings.

SUBJECTS AND ME T H O D S

The data for this study are all prospec­tive, and include some patients who have been described previously.10 All 200 pa­tients were older than age 60 years. Of the 200 cases reported, 111 had iris clip lenses, 55 had Sputnik lenses, and 34 were without implants. Follow-up was at least one year. Surgery consisted of a limbal-based flap, superior groove forma­tion with the placement of at least three preplaced sutures, forceps or cryoextrac-tion of the lens, and insertion, using closed eye techniques of either a Rayner iris clip, Fyodorov Sputnik, or no lens.11

Any operative or postoperative complica­tion, primarily vitreous loss at surgery or loop dislocation postoperatively, disqual­ified the patient from the series. Preopera-tive central corneal endothelial cells were counted by using the fixed frame count­ing method taking an average of four or more photographs for each eye. Postoper­atively, cells were counted daily for three days, every third day for ten days, weekjy for the next two weeks, monthly for the next three months, and then at three-month intervals.

R E S U L T S

The Table lists the average percentage of cell loss (± standard error of the mean) at fixed periods after cataract surgery

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94 AMERICAN JOURNAL OF OPHTHALMOLOGY JULY, 1979

TABLE E F F E C T O F CATARACT EXTRACTION W I T H AND W I T H O U T IMPLANTATION ON PERCENTAGE

REDUCTION IN CENTRAL C E L L DENSITY AT FIXED PERIODS AFTER SURGERY

Reduction of Endothelial Density with Time Time Iris Clip Sputnik Without Implant

1-2 days

3-5 days

7-10 days

2-3 wks

1 mo

2 mos

3 mos

6 mos

1 yr or more

4.1 ± 1.7 (N = 62) 9.5 ± 2.7 (N = 84)

15.1 ± 2.9 (N = 71)

20.2 ± 4.7 (N = 90)

23.5 ± 3.0 (N = 96)

26.4 ± 3.1 (N = 84)

30.4 ± 3.3 (N = 80)

31.8 ± 1.8 (N = 73)

32.0 ± 2.6 (N = 65)

3.6 ± 1.5 (N = 44) 9.0 ± 4.0 (N = 47)

11.5 ± 0.8 (N = 27)

14.5 ± 5.7 (N = 49)

16.2 ± 3.9 (N = 51)

20.5 ± 3.0 (N = 47)

23.9 ± 6.7 (N = 49)

24.8 ± 3.9 (N = 40)

24.4 ± 2.9 (N = 39)

4.5 ± 1 (N = 30)

4.9 ± 1.7 (N = 22) 6.5 ± 2.3 (N = 42) 8.8 ± 1.8 (N = 30)

10.6 ± 2.2 (N = 31)

11.3 ± .9 (N = 24)

13.0 ± 3.1 (N = 22)

13.1 ± 4.0 (N = 20)

14.4 ± 4.3 (N = 18)

without an implant or with the placement of a Rayner iris clip or Fyodorov Sputnik lens. The cell counts altered little during the first week, and then progressively diminished until they became somewhat asymptotic at three months. Reductions of approximately 25 to 30% occurred in implanted eyes, and 10 to 15% in nonim-planted eyes (Figure).

DISCUSSION

We have shown in the cat that most of the steps of a cataract extraction do not seriously reduce central endothelial den­sity.9 Incision, irrigation, folding, and air

injection reduce central endothelial den­sity about 5 to 10% in this animal. These changes occur within three months (pre­dominantly within one month) and stabi­lize. If the endothelium is deliberately denuded, however, the cell loss is much greater, reaching about 22% when 27 mm2 are abraded. Again, a reduction in cell count appears to stabilize at the three-month period.

The clinical data of the present study and other studies indicate that iris-supported intraocular lens implantation will reduce central endothelial cell densi­ty in the range of 25 to 30%, approximate-

Figure (Galin and associates). Graphic representation of central cell loss after routine and pseudo-phakic cataract extraction. Upper trace is nonimplanted eyes, lower trace implanted eyes.

VOL. 88, NO. 1 CORNEAL ENDOTHELIAL CELL DENSITY 95

ly twice that which will be experienced by simple cataract extraction. Further, in uncomplicated extractions of either type, the cell count at three months is close to the maximum that has resulted from the procedure. Other factors such as age, in­flammation, nature of healing, and many unknown factors account for any future reduction of cells.

If certain steps or their avoidance alter cell density, 90-day values should be compared. Further, the area photo­graphed must always be stated. A definite vertical disparity in cell density after cat­aract extraction is evident, and superior corneal counts in one study compared to central or inferior counts in another are of little value.12 Because it is difficult to place the dipping cone of present specu­lar microscopes near a fresh wound and get good photographs, we presented the data from only the central photographs, although multiple areas of the cornea were photographed. Central reductions were significantly less than the reduc­tions in the area of the wound, although these too seemed to stabilize at about 90 days, at least with respect to the density of cells.

Because animal and control studies in­dicate that implantation creates far more cell loss than cataract extraction alone, we assume that the steps of implantation or the prosthesis itself cause this differ­ence.4 We have been unable to show tissue culture toxicity from a variety of implants in short-term experiments13 (un­published data). Further, if implants were causing central cell loss on a long-term, toxic basis, we would expect differing slopes for central cell counts in implanted and nonimplanted eyes after 90 days, which has not been found. Cell function may be adversely influenced by factors such as chronic inflammation, not picked up simply by counting cells, and these may contribute to the higher incidence of

long-term corneal decompensation in the implanted eye.

It appears that the predominant cause of rapid central endothelial cell loss after implantation is caused by surgical manip­ulation. The rate at which this occurs as well as the cessation of decline after 90 days imply a mechanical cause, and that elimination of this cell loss is best achieved by mechanical means. These may include significant change in cataract technique, the use of glides and lens covers, and, ultimately, lens coatings. Ev­idence that any or all of these methods are effective can only be shown by serial cell counts with absolute comparisons at the 90-day period. The causes of alteration in cell function, which may ultimately be more important that cell density, are un­known.

SUMMARY

Serial endothelial photographs were taken preoperatively and postoperatively in 200 eyes; 111 eyes contained a Rayner iris clip lens, 54 eyes contained a Fyodo-rov Sputnik lens, and 35 eyes had no lens. Central endothelial cell density was changed in all instances, with counts in implanted eyes declining 25 to 30%, and in nonimplanted eyes 10 to 15%. In both instances, the decline essentially ceased at about three months. The cause of the greater decline in implanted eyes ap­peared to be mechanical and subsequent cell loss after the 90-day period was virtu­ally equal for the two groups. Methods that may be used to alter the difference in cell density occurring with implantation are best analyzed by using the 90-day period data for comparison.

REFERENCES 1. Hoefle, F. B., Maurice, D. M., and Sibley,

R. C : Human corneal donor material. A method of examination before keratoplasty. Arch. Ophthalmol. 84:741, 1970.

96 AMERICAN JOURNAL OF OPHTHALMOLOGY JULY, 1979

2. Binkhorst, C. D., Nygaard, P., and Loones, L. H.: Specular microscopy of the corneal endothe-lium and lens implant surgery. Am. J. Ophthalmol. 85:597, 1978.

3. Jaffe, N., Galin, M. A., Hirschman, H., and Clayman, H.: Pseudophakos. St. Louis, C. V. Mosby, 1978, p . 91 .

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

5. Sheets, J. H., and Maida, J.: Lens glide in implant surgery. Arch. Opthalmol. 96:145, 1978.

6. Bourne, W. M., and Kaufman, H. E.: Endothe-lial damage associated with intraocular lenses. Am. J. Ophthalmol. 81:482, 1976.

7. Forstat, S. L., Blackwell, W. L., Jaffe, N. S., and Kaufman, H. E.: The effect of intraocular lens im­plantation on the corneal endothelium. Trans. Am. Acad. Ophthalmol. Otolaryngol. 83:195, 1977.

8. Hirst, L. W., Snip, R. C , Stark, W. J., and Maumenee, A. E.: Quantitave corneal endothelial

evaluation in intraocular lens implantation and cata­ract surgery. Am. J. Ophthalmol. 84:775, 1977.

9. Galin, M. A., Fetherolf, E., Lin, L., and Sugar, A.: Experimental cataract surgery. Ophthalmology In press.

10. Sugar, A., Fetherolf, E., Lin, L., Obstbaum, S., and Galin, M. A.: Endothelial cell loss from intraocular lens insertion. Ophthalmology 85:394, 1978.

11. Galin, M. A.: Intraocular lenses and surgical technique. The Fyodorov lens. In Transaction Uni­versity of Illinois Symposium on Intraocular Lens­es. New York, Appleton-Century-Crofts, 1977, pp. 42-44.

12. Hoffer, K. J., and Phillippi, G.: A cell mem­brane theory of endothelial repair and vertical cell loss after cataract surgery. Am. IOL Implant Soc. J. 4:18, 1978.

13. Galin, M. A., Turkish, L., and Chowchuvech, E.: Detection, removal, and effect of unpolymerized methylmethacrylate in intraocular lenses. Am. J. Ophthalmol. 84:153, 1977.

O P H T H A L M I C MINIATURE

. . . the truth is that the knowledge of external nature and of the sciences which that knowledge requires or includes, is not the great or the frequent business of the human mind. Whether we provide for action or conversation, whether we wish to be useful or pleasing, the first requisite is the religious and moral knowledge of right and wrong; the next is an acquaintance with the history of mankind, and with those examples which may be said to embody truth, and prove by events the reasonableness of opinions. Prudence and justice are virtues, and excellencies, of all times and of all places; we are perpetually moralists, but we are geometricians only by chance. Our intercourse with intellectual nature is necessary; our speculations upon matter are voluntary, and at leisure. Physical knowledge is of such rare emergence, that one man may know another half his life without being able to estimate his skill in hydrostatics or astronomy; but his moral and prudential character immediately appears.

Samuel Johnson, Life of Milton