Morphological Variations in Corneal Endothelium Following Keratophakia and Keratomileusis JAMES V. AQUAVELLA, MD,* FRANCISCO BARRAQUER, MD,t GULLAPALLl N. RAO, MD,* LUIS A. RUIZ, MOt

Abstract: We studied in vivo endothelial cell morphology, using the specular microscope, in both eyes of 31 patients who underwent refrac­tive keratoplasty at the Clinica Barraquer. The postoperative cell density following myopic and hypermetropic keratomileusis was reduced when compared to preoperative figures in the same eye or unoperated fellow eye. The reduction was greatest when hypermetropic keratomileusis was combined with cataract extraction at the same procedure. None of the cases developed structural abnormalities or sequelae of inflammatory reaction, such as precipitates on the endothelium. [Key words: cell den­sity, corneal endothelium, endothelial morphology, keratomileusis, keratophakia, refractive keratoplasty, specular microscopy.] Ophthal­mology 88:721- 723, 1981

Following the introduction of the technique of re­fractive keratoplasty for the surgical correction of aphakia,l a number of authors have reported im­provements in the techniques of keratomileusis and keratophakia. 2- 4 Troutman and Swinger5 suggested that the techniques have evolved to the point where they could be considered a reasonable alternative to the implantation of alloplastic lens substitutes in the cor­rection of surgical aphakia.

In 1979 we called attention to the principal areas of concern with these keratorefractive procedures and suggested an analysis comparing the risks and benefits of intraocular lens implantation, extended wear con­tact lenses, and refractive keratoplasty (keratophakia and keratomileusis).6 Numerous reports have con-

From the Departments of Ophthalmology at University of Rochester School of Medicine and Dentistry' and The Clinica Barraquer,t and the Department of Ophthalmology Park Ridge Hospital, Rochester, New York.'

Presented at the Eighty-fifth Annual Meeting of American Academy of Opthalmology Chicago, Illinois, November 2-7, 1980.

Reprint requests to James V. Aquavella, MD, 1160 Chili Avenue Rochester, NY 14624.

0161-6420/8110800/07211$00.65 © American Academy of Ophthalmology

firmed the importance of comprehensive morphologi­cal study of corneal endothelium, in an attempt to de­termine functional capacity. In the present study we examined the morphological effects of keratophakia and hypermetropic keratomileusis on corneal en­dothelium using the techniques of clinical specular mi­croscopy and automated image analysis.

MATERIALS AND METHODS

We examined both eyes of 27 patients who under­went refractive keratoplasty at the Clinica Barraquer. Fourteen of these eyes had cataract extraction com­bined with keratomileusis, (group 1) five eyes had hypermetropic ketatomileusis (group 2), and eight other eyes had myopic keratomileusis (group 3).

Specular microscopy was performed by one of us (FB), using a Heyer-Schulte specular microscope. A Nikon camera was attached to the microscope and Kodak Tri-X 400 ASA film was used in all Cases. Photographs were taken of the central corneal en­dothelium in both operated and control eyes. At each of these examinations, central corneal thickness was

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OPHTHALMOLOGY • AUGUST 1981 • VOLUME 88 • NUMBER 8

also obtained using the pachometer attached to the specular microscope.

Photographs were subjected to specialized photo­graphic process to enhance the contrast of the borders. Overlays were then made of the magnified image of these cells, which were then subjected to automated image analysis using Zeiss-MOP III instrument.

Analysis of specular photomicrographs was con­ducted according to a previously reported technique. 7

Qualitative analysis included observations under good illumination and magnification. We attempted to dem~ onstrate abnormalities such as changes in shape, pre­cipitates on endothelium, and a cellular areas (guttata-like).

Quantitative analysis evaluated the parameters of cell density, mean cell area, and a coefficient of varia­tion cell area (polymegathism quotient). Statistical analysis was performed on the data from the operated eyes and the control group. Either the preoperative endothelia:! cells data (PO) or the data on the en­dothelium of the opposite eye (OE) was used as con­trols. Mean endothelial cell density (ECD) and stan­dard deviation were computed for each group. An analysis of the data given was performed using T-test for matched pairs.

RESULTS

The data on all the cases is shown in Tables 1 and 2. In the group where cataract extraction was per­

formed along with keratomileusis , the mean ECD of the unoperated eye was 2254 cells/sq mm, with the postoperative value being 1822 demonstrating a mean cell loss of 18% (P < 0.01) with a range of6.2 to 30.3%.

In the hypermetropic keratomileusis in the aphakia

group, the preoperative ECD ranged from 1612 cells/sq mm to 2777 cells/sq mm, with a mean value of 2420 cells/sq mm. The postoperative values ranged from 1323 to 2604 cells/sq mm, with a mean vlaue of 1984, giving a mean cell loss of apout 18%. The percentage cell loss ranged from 2.4 to 49.1 (P < 0.12).

In cases of myopic keratomileusis , the correspond­ing preoperative ECD ranged from 2244 to 4030 cells/sq mm, with a mean value of 3229 cells/sq mm. The cell density following surgery ranged from 2046 to 3844 cells/sq mm, with a mean value of 3023 cells/sq mm. In terms of percentage cell loss, this ranged from o to 10.8, with a mean value of 6.2 (P < 0.01).

A comprehensive analysis of these data indicate that all these procedures were associated with some degree of endothelial trauma with myopic keratomileusis pro­ducing least damage and hypermetropic kerato­mileusis , combined with cataract extraction, asso­ciated with the greatest degree of cell damage. Statisti­cally, the difference between the cornea endothelium not subjected to these surgical procedures and the corneal endothelium following this procedure was sig­nificant in groups 1 and 3. While the same trend was evident in group 2, the sample size was too small to arrive at any valid statistical significance. . The coefficient of variation in cell area did not dem­onstrate any significant attenuation following these procedures.

Qualitative analysis of the specular photomicro­graphs revealed no evidence of precipitates or cell free areas . There was some evidence of alteration in cell shape in these cases associated with greater degrees of cell loss.

Corneal thickness measurements did not reveal any significant alteration from preoperative values except in the group of myopic ~eratomileusis when all but two cases demonstrated a reduction.

Table 1. Cataract Extraction with Keratomileusis

Cell Density (ECDt) (Cells/sq mm) CVt CTt

Preop/Dpp Eye Postop % Loss/Diff Preop/Dpp Eye Postop Preop/Dpp Eye Po stop

1. 2666 (PD§) 2108 20.9 72 .9 (P.O.) 65.0 0.53 0.48 2. 1984 (DE") 1612 18.8 78.8 61.8 0.56 0.48 3. 2232 (DE) 1555 30.3 56.7 43.9 0.53 0.51 4. 1227 (DE) 868 29.2 39.2 41.8 0.52 0.42 5. 2356 (PO) 1860 21.1 27.2 39.1 0.52 0.72 6. 1612 (PO) 1488 7.7 42 .3 29.8 0.55 0.55 7. 1240 (DE) 1116 10.0 38.4 27.9 0.55 0.53 8. 2666 (DE) 2170 18.6 56 .9 51.4 0.48 0.51 9. 992 (PO) 930 6.2 39 .6 33.8 0.59 0.55

10. 2418 (DE) 1922 20 .5 29.13 39 .2 0.53 0.52 11. 2790 (DE) 2480 11 .1 49.8 29.6 0.55 0.55 12. 2356 (DE) 2046 13.2 54 .6 48.9 0.53 0.55 13. 2480 (DE) 1984 20.0 38.5 46.7 0.52 0.45 14. 2976 (DE) 2542 14.6 28.9 24.6 0.55 0.59

• ECD: Endothelial cell density; t CV: Coefficient of variation in cell area; :j: CT: Corneal thickness in mm; § PO: Preoperative; II OE: Opposite normal eye.

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AQUAVELLA • MORPHOLOGICAL VARIATIONS

Table 2. Hypermetropic and Myopic Keratomileusis

Cell Density (ECD') (Cells/sq mm) CVt Cll

Preop/Opp Eye Postop % Diff Loss Preop/Opp Eye Postop Preop/Opp Eye Postop

Hypermetropic keratomileusis 1. 2542 (PO§) 2482 2.4 80 .1 65 .6 0.47 0.54 2. 2563 (PO) 2067 19.3 71.4 68.2 0.49 0.48 3. 1612 (PO) 1448 10.2 33 .8 41.9 0.54 0.51 4. 2604 (PO) 1323 49.1 27 .9 38.8 0.54 0.54 5. 2777 (PO) 2604 6.2 19.8 28.2 0.52 0.50

Myopic keratomileusis 1. 3390 (PO) 3038 10.4 27.0 23.0 0.49 0,50 2. 3906 (PO) 3844 1.5 35 .9 31.4 0.47 0.43 3. 3658 (PO) 3372 7.8 66 .5 60.1 0.47 0.38 4. 2244 (OEi') 2046 8.8 27.2 37.2 0.58 0.47 5. 3038 (PO) 2776 8.6 37 .7 27.2 0.47 0.51 6. 2776 (PO) 2728 1.7 60 .1 80 .0 0.49 0.46 7. 4030 (PO) 3596 10.8 35 .9 42.4 0.52 0.47 8. 2790 (OE) 2790 0 65 .7 61.0 0.43 0.43

ECO: Endothelial cell density; CV: Coefficient of variation in cell area; CT: Corneal thickness in mm; PO: Preoperative; OE: Opposite normal eye .

DISCUSSION

The results of this study must be interpreted cau­tiously. Despite access to the largest existing patient population, the logistics of attempting to follow these patients are such that long periods of time are neces­sary to collect a sufficient number of cases for statisti­cal significance. Yet a number of subtle changes in technique are necessarily introduced in the course of time.

We can, however, make some observations. There were no signs of precipitates , cell free areas, (guttata­like area), or other morphological changes such as were demonstrated in a similar study of patients who had undergone intraocular lens implantation. 8

While it would seem that some cell loss follows all of these procedures, the percentage cell loss is obviously greater when cataract extraction was combined with refractive keratoplasty in the same procedure. Clearly, this is insufficient evidence to indicate that such com­bined procedures should not be done. In fact, we have no evidence of the practical significance of even large degrees of cell loss per se. Even if cell loss could be significantly reduced by performing hypermetropic keratomileusis after a delay of six to 12 months (fol­lowing cataract extraction), any perceived benefit may be discounted on terms of quality or longevity of the visual result. The cost and added time of visual re­habilitation must also be considered.

While in the intraocular lens study there is a strong possibility that endothelial changes are related to in­flammation, in the present study observed changes were perceived as definitely related to the surgical procedure.

Future study of the same population will reveal if there has been any additional change in cell density or shape with time. Preliminary data suggest that, in contrast to the intraocular lens study, this is not the case. Thus, refractive keratoplasty may well have the potential of, or less risk than, the intraocular lens when viewed from the perspective of endothelial morpho­logical changes as a result of inflammation.

REFERENCES

1. Barraquer JI. Discussion. In: King JH, Jr, McTigue JW, eds. The Cornea World Congress. Washington: Butterworths, 1965; 691-3.

2. Barraquer JI. Refractive keratoplasty I. In: Barraquer JI , ed. Compilation of Reprints . Bogota: Instituto Barraquer de America, 1970.

3. Barraquer JI. Refractive Keratoplasty II : C.R. du Primum Forum Ophthalmologicum, Bogota: Instituto Barraquer de America, 1970; Bogota (A paraitre).

4. Ainsl ie D. The surgical correction of refractive errors by keratomileusis and keratophakia . Ann Ophthalmol 1976; 8:349-67.

5. Troutman RC, Swinger CA. Refractive keratoplasty: kerato­phakia and keratomileusis. Trans Am Ophthalmol Soc 1978; 76:329-39.

6. Aquavella, JV. Discussion of paper by Dr. Richard C. Trout­man, et al. Ophthalmology 1979; 86:531-3.

7. Rao GN, Shaw EL, Stevens RE, Aquavella JV. Automated pattern analysis of corneal endothelium. Ophthalmology 1979; 86: 1367 - 73.

8. Rao GN, Stevens RE, Harris JK, Aquavella JV. Long-term changes in corneal endothelium following intraocular lens im­plantation. Ophthalmology 1981; 88:386-97.

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