VERTICAL E N D O T H E L I A L C E L L DISPARITY K E N N E T H J. H O F F E R , Santa Monica,
The specular microscope was invented by Maurice 1 and modified for clinical use by Bourne and Kaufman. 2 Its clinical applications have so far documented sev eral findings regarding the status of the corneal endothelial population both be fore and after anterior segment proce dures. Endothelial cell density can be from 1,600 to 4,000 cells/mm 2 in unoperated eyes. 2 Comparisons of preoperative and postoperative central corneal cell counts have shown a 10 to 15% aver age cell loss after intracapsular cataract extraction. 3 Central cell losses averaging 35% were demonstrated in counts taken in lens implant cases done by open sky implantation techniques 4 and 14% when implanted with deep chamber closed-eye techniques. 5 A 67% cell loss was noted after traumatic lens implantation, as com pared to a 16% loss with atraumatic im plantation. 6 Phacoemulsification has been reported to cause a 50% increase in cell loss over intracapsular extraction. 7 Based on a small series, Blackwell, Gfavenstein, and Kaufman 8 identified a uniform distribution of cell density com paring peripheral and central areas of the cornea in both preoperative and postoper ative eyes, thus postulating central counts as representative of the entire cornea. 8 We report herein a study on a large series of postoperative corneas to determine whether a central count was a true indica tion of the endothelial cell population in all areas of the cornea. From the Jules Stein Eye Institute, UCLA and Santa Monica Hospital Eye Laboratory, Santa Monica, California. This study was supported by a grant from Heyer-Schulte Medical Optics Center. , Reprint requests to Kenneth J. Hoffer, M.D., 2001 Santa Monica Blvd., 460-W, Santa Monica, CA 90404. 344
M.D.
California METHODS
All subjects in this study were random ly selected from patients referred to us for routine postoperative central endothelial counts. A Syber endothelial specular mi croscope was used for all endothelial photography. 2 To obtain photographs in the superior and inferior cornea that would be reproducible, a system of posi tioning was devised. A simple fixation light device from a slit lamp was attached to the chin rest assembly of the endotheli al camera. This was used to aid the pa tient in maintaining the appropriate gaze. While the endothelium was observed through the sighting of the camera, the patient was instructed to look up (or down) until, with proper camera cone adjustment, the endothelium could no longer be seen (exceeding peripheral limit of photography). The fixation device was then moved slowly in the opposite direc tion until a clear image of endothelial cells could be photographed. Assurance of position was checked by intermittent gross observations of the eye. This posi tion was found to be approximately 2 mm from the corneoscleral limbus superiorly and inferiorly. The fixation device used by Blackwell, Gravenstein, and Kaufman 8 was not available or used in this study. Six to ten photographs were taken in each area and three of the best from each area were selected for printing and counting. Counting was performed by totalling the number of all whole and partial cells touching one horizontal and one vertical edge of the print. The mean of the three photographs of each set was multiplied by our magnification factor (x 74), arrived at by comparison with an initial photo graph of a micrometer scale, to arrive at the cell density in cells per square milli-
AMERICAN JOURNAL O F OPHTHALMOLOGY 87:344-349, 1979
VOL. 87, NO. 3
VERTICAL E N D O T H E L I A L C E L L DISPARITY
meter. A coding of each photograph was used to insure accurate documentation. One eye each of 59 patients ranging in age from 46 to 89 years, average age 72 years, was photographed in this manner. Thirty-four patients underwent phacoemulsification and 31 of these received a lens implant. Twenty-five patients under went intracapsular cataract extraction and 20 of these received lens implant. In all cases phacoemulsification was performed through a 12 o'clock superior incision (photography was performed in this area). These procedures were performed by var ious surgeons using varying techniques and lens styles. A separate series of 23 normal control (unoperated) eyes were photographed in a similar manner. The 23 patients ranged in age from 21 to 85 years; the average age was 53 years. RESULTS
Vertical cell disparity counts performed on the first six normal control eyes sub stantiated the uniform population shown by Kaufman. 8,9 Figure 1 shows the uni form vertical density in an eye with a high cell count; Figure 2 shows uniform verti cal density in an eye with a low cell count. An evaluation of the vertical counts of all 23 control eyes revealed no trend of disparity between the superior and inferior regions (Table 1). Vertical cell disparity is defined as the percentage
345
change in cell density from the inferior count to the superior count I-S
I.
The
vertical cell disparity of the control eyes ranged from - 3 5 % to +35% with a mean of - 4 % (Table 1). The results of the first six postoperative patients indicated a def inite vertical disparity in cell density be tween the superior and inferior cornea. 9 Figure 3 shows the cell populations of a recently operated eye (two weeks); Figure 4 shows an eye operated on three years before examination. Table 2 shows the cell counts of the 59 subject eyes. The vertical cell disparity in this group ranged from —38% to +38% with a mean of +40%, compared to the mean of —4% of the control group. Of the subject eyes, 97% showed a positive vertical cell dis parity, as compared to 43% in the control group. The disparity between the superi or and inferior cornea did not depend on the interval between surgery and photog raphy. Vertical disparity was noted in eyes with low postoperative cell counts (Fig. 5). In the subject group, 52 eyes (87%) showed a definite superior-inferior gradi ent in which the highest cell count was inferior and the lowest was superior. An other six eyes (10%) showed higher cen tral than inferior cell counts, but in these cases the superior count was still the lowest of the three areas. Only one eye (2%) showed a higher cell count in the
SUPERIOR 2787
j^-W^..^' ■■vLk
CENTRA! 2664
.»%•. * j p w INfERIOR 234'J
Fig. 1 (Hoffer). Vertical cell counts on a preoperative normal control eye in a 61-year-old patient.
INFERIOR 715
Fig. 2 (Hoffer). Low vertical counts on a preoperative normal control eye in an 84-year-old patient.
346
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH, 1979
TABLE 1 V E R T I C A L C E L L C O U N T S , C O N T R O L S : C E L L DENSITY ( C E L L S / M M 2 ±
Patient No.
Age (yrs)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
26 21 40 21 79 27 59 84 81 72 61 84 72 73 66 66 21 21 85 22 22 46. 73
Mean
SD*)
VCD
Superior
Central
Inferior
VCM
(%)
2688 : 151 2837 : 229 2 4 6 7 : : 178 2639 : 85 2442 210 3577 : 143 1727 : 178 2664 : 201 691 : 34 2491 : 170 3009 : 200 592 : 58 1579 : 121 2960: 204 2787 : 210 2319: 158 3330 : 232 2935 : 213 1899 : 187 3330 : 179 3651 : 235 2590: 187 2245: 150 2451
2368 144 2738 187 2516 203 2220: 165 2565 142 3059: 99 1950: 110 2343 : 221 962 53 2664 : 200 2319 ; 191 765 : 78 1850 : 113 2171 : 175 2664: 201 2245 : 187 3083 : 223 3281 : 340 1776 : 187 3281 : 225 3305 : 243 2146 : 178 2294 : 199 2328
2738 : 168 2615: 200 2294 : 164 2417 : 178 197 2491 2960 : 203 2442 : 194 2541 : 210 1061 : 75 2615: 194 2713 : 176 715 : 54 1603 : 111 2516 : 187 2343 : 200 2245 : 191 2960 : 127 3182 : 178 2146 : 161 3108 : 213 2837 : 198 1924 : 100 2368 : 186 2360
2598 2730 2426 2425 2499 3199 2040 2516 905 2590 2680 691 1677 2549 2598 2270 3124 3133 1940 3240 3264 2220 2302 2388
2 - 8 2 -21 29 - 5 35 5 -11 17 2 -18 -19 - 3 -13 8 12 - 1 -29 -35 5 - 4
*VCM designates vertical cell mean; VCD, vertical cell disparity (difference between superior and inferior count) I-S I
superior area. Similar findings were first noted by J. Flaxen (personal communica tion, 1978) in studies of postcataract ca daver corneas by direct regional counting of cells by light microscopy. A comparison of the means of the re gional densities was made between the
INFfRIOH 2514
Fig. 3 (Hoffer). Vertical cell disparity (45%) in an eye of a 61-year-old patient two weeks after phacoemulsification and lens implant.
controls and subjects (Fig. 6). A 2 3 % infe rior cell loss was evident compared to twice that (46%) in the superior area (Table 3). The central cell loss (38%) compared well with previous studies 4 as well as to the vertical cell mean loss (39%) of averaging all three areas (Table 3).
INftRIO* H55
Fig. 4 (Hoffer). Vertical cell disparity (36%) in an eye of a 46-year-old patient three years after phacoemulsification and lens implant.
TABLE 2 V E R T I C A L C E L L C O U N T S , SUBJECTS: C E L L D E N S I T Y ( C E L L S / M M 2 ) ±
atient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Mear i
Age (yrs)
Surgery
47 47 61 57 80 64 69 46 66 46 73 75 49 52 52 70 86 61 64 63 74 74 64 77 77 46 81 79 57 61 61 76 78 69 72 62 75 75 75 80 58 65 77 70 77 81 77 89 74 74 68 75 73 73 79 79 55 65 58
PKE PKE PKE ICCE ICCE ICCE ICCE ICCE PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL
Post-Operative
Superior
Central
SD*
Inferior
VCM
VCD
(%) 3 mos 15 mos 4V2 yrs 4 yrs 2 yrs 7 yrs 8V2 yrs 4 mos 20 mos 3 yrs 5 yrs 4 mos 4 mos 2 mos 2 yrs 2 yrs 3 yrs 2 wks 3 yrs 2 mos 3V2 yrs 6 mos 1 wk 4 mos 1 mo 3 yrs 3 yrs 2 yrs 3 mos 2 mos 3 yrs 3 mos 3 mos 2 yrs 2 mos 2 mos 2 yrs 9 mos 2 yrs 4 mos 7 mos 3 mos. 4 mos 18 mos 4 mos 5 mos 3 mos 1V2 yrs 2 yrs 3 yrs 4 yrs 3 mos 4 yrs 4 yrs 3 mos 2 mos 2 mos 4 mos 3 mos
1776 1159 1233 937 1480 617 567 1258 1233 1036 1159 1209 740 1233 1924 789 789 1381 592 1307 888 1209 1776 962 1406 937 616 666 1505 1258 765 1061 888 789 1554 1110 691 937 666 691 1554 1110 1776 1455 1431 740 1110 493 666 1357 962 1036 814 839 1924 1702 1036 1061 666 1093
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± + ±
187 219 152 87 200 53 21 87 152 121 200 127 86 216 187 84 21 126 49 28 11 201 186 36 99 102 48 110 176 144 187 200 106 48 212 165 87 105 49 110 110 87 128 210 87 100 121 81 38 143 42 100 96 152 171 153 129 87 101
2467 ± 243 1603 ± 145 2146 ± 161 1554 ± 102 1603 ± 164 592 ± 83 740 ± 56 1085 ± 122 2097 ± 201 1455 ± 187 1135 ± 176 1727 ± 145 1209 ± 123 1875 ± 184 1776 ± 191 691 ± 100 1061 ± 201 1850 ± 187 641 ± 24 1751 ± 121 888 ± 87 1751 ± 124 2121 ± 200 1307 ± 113 2097 ± 187 1282 ± 124 740 :± 93 666 ± 46 1899 ± 119 1924 ± 186 1184 ± 124 1800 ± 136 1455 ± 200 1036 ± 147 1924 ± 200 Guttatat 1061 ± 121 1381 ± 138 839 ± 146 863 ± 27 1998 ± 210 2220 ± 187 2023 ± 302 2097 ± 144 2171 ± 169 937 ± 110 2664 ± 203 567 ± 46 937 ± 119 1727 ± 287 937 ± 101 1875 ± 186 715 ± 110 863 ± 147 2072 ± 128 1061 ± 200 1085 ± 143 2294 ± 187 789 ± 46 1610
2985 ± 2763 ± 2097 ± 2615 ± 2368 ± 937 ± 937 ± 2245 ± 2467 ± 1653 ± 1283 ± 1653 ± 2343 ± 2195 ± 2541 ± 1061 ± 962 ± 2516 ± 913 ± 2072 ± 1209 ± 1949 ± 2269 ± 2615 ± 2171 ± 1455 ± 863 ± 987 ± 2368 ± 1949 ± 1307 ± 1776 ± 2393 ± 1307 ± 2294 ± 1825 ± 1307 ± 1831 ± 1258 ± 1159 ± 2171 ± 2491 ± 2689± 2442 ± 2639 ± 1899 ± 2442 ± 617 ± 1209 ± 2146 ± 1159 ± 1307 ± 666 ± 1700 ± 2368 ± 1431 ± 2097 ± 2491 ± 913 ± 1819
114 129 230 315 186 111 87 128 138 200 46 118 213 196 202 87 58 200 161 212 100 128 302 229 144 201 110 86 245 186 0 150 198 102 210 187 113 129 147 55 187 301 506 127 210 187 164 127 145 183 111 119 42 0 203 89 200 146 121
2409 1842 1825 1702 1817 715 748 1529 1932 1381 1192 1530 1431 1768 2080 847 937 1916 715 1710 995 1636 2055 1628 1891 1225 740 773 1924 1710 1085 1546 1579 1044 1924 1468 1020 1233 921 904 1908 1940 2163 1998 2080 1192 2072 559 937 1743 1019 1406 731 1134 2121 1398 1406 1950 790 1507
41 58 43 60 37 39 52 44 50 37 12 30 68 44 44 35 26 45 35 37 27 38 22 63 35 36 29 33 36 35 41 41 63 40 32 39 47 32 47 40 28 55 34 40 46 61 58 20 45 37 19 45 -18 51 19 -38 51 57 27 40
*PKE designates phacoemulsification; ICCE, intracapsular cataract extraction, IOL, intraocular lens; VCM, vertical cell mean; VCD, vertical cell disparity (difference between superior and inferior count) fl-S"l. f Unable to count. ,
348
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH, 1979
TABLE 3 C E L L LOSS COMPARISON O F C O N T R O L AND SUBJECT G R O U P S *
Means
INfERIOR 2393
Fig. 5 (Hoffer). Vertical cell disparity (63%) in an eye of a 78-year-old patient with large postoperative cell loss three months after phacoemulsiflcation and lens implant.
Controls Subjects Cell loss,
%
Superior Counts
Central Counts
Inferior Counts
VCM
2451 1094 46
2328 1452 38
2360 1818 23
2388 1455 39
*VCM designates vertical cell mean.
taining central and not peripheral counts when comparing preoperative and post operative central cell counts. Evaluating cell populations in all areas of the cornea is important before performing secondary procedures on previously operated eyes. An inferior or temporal-nasal approach may be safer to a cornea with low cell density superiorly. Once a damaged area of the cornea is covered by endothelial cells the stimulus for cell movement stops until cell mem brane contact is lost by dying cells or further damage.
DISCUSSION
These data indicate a need to broaden our view when estimating endothelial cell losses. Endothelial damage is much high er in the superior area of the cornea where the incision is made and most manipula tions are performed. The inferior area of the cornea is the least affected by intra ocular procedures. Central counts are more a mathematical average of cell density than an indicator of overall uniform density, and time does not appreciably alter the vertical cell disparity caused by surgical trauma. Only long range pro SUMMARY spective studies of postoperative eyes will Endothelial cell counts were performed conclusively document the lack of uni postoperatively in superior, central, and form density healing after surgical trau inferior areas of the cornea in 59 patients. ma. No regional differences were found in a Diligence must be maintained in obseries of 23 preoperative control cataract eyes. A definite, large density disparity was noted in 58 of the 59 postoperative corneas studied. Disparity was high nine years as well as two weeks postopera tively. These data indicated the necessity for accuracy of positioning in postopera tive comparison studies and the necessity for regional cell counts before secondary surgical procedures. MEAN CELLS PER M M ;
2500 -
2000 -
1500 -
INFERIOR
CENTRAL CORNEAL
SUPERIOR
LOCATION
Fig. 6 (Hoffer), Graphic comparison of mean inferior central and superior cell counts in the control and subject series.
ACKNOWLEDGMENT
Gregory W. Phillippi provided the vertical cell studies and developed the application of the tech nique.
VOL. 87, N O . 3
VERTICAL E N D O T H E L I A L C E L L DISPARITY
REFERENCES 1. Maurice, D. M.: Cellular membrane activity in the corneal endothelium of the intact eye. Experientia. 24:1094, 1968. 2. Bourne, W. M., and Kaufman, H. E.: Specular microscopy of human corneal endothelium in vivo. Am. J. Ophthalmol. 81:319, 1976. 3. : Cataract extraction and the corneal en dothelium. Am. J. Ophthalmol. 82:44, 1976. 4. Forstot, S. L., Blackwell, W. L., and Jaffe, N. S.: Effect of intraocular lens implantation on the corneal endothelium. Trans. Am. Acad. Ophthalmol. Otolaryngol. 83:195, 1977. 5. Hirst, L. W., Snip, R. C , Stark, W. J., and Maumenee, E.: Quantitative corneal endothelial
349
evaluation in intraocular implantation and cataract surgery. Am. J. Ophthalmol. 84:775, 1977. 6. Sugar, J., Mitchelson, J., and Kraff, M. C : Endothelial trauma and cell loss from intraocular lens insertion. Arch. Ophthalmol. 96:449, 1978. 7. Sugar, J., Mitchelson, J., and Kraff, M. C : The effect of phacoemulsification on corneal endothelial cell density, Arch. Ophthalmol. 96:446, 1978. 8. Blackwell, W. L., Gravenstein, N., and Kauf man, H. E.: Comparison of central corneal endothe lial cell numbers with peripheral areas. Am. J. Ophthalmol. 84:473, 1977. 9. Hoffer, K. J., and Phillippi, G.: A cell mem brane theory of endothelial repair and vertical cell loss after cataract surgery. Am. Intra-Ocular Implant Soc. J. 4:18, 1978.
O P H T H A L M I C MINIATURE
. . . the uncertainty, under which we still remain, in regard to the virtue of the waters of Bath. Few medicines have been more repeatedly tried under the inspection of such numerous and able judges; and yet we have had in the present age a dispute between those who by their experience and sagacity were best qualified to decide this question, in which one side asserted that paralytic patients were cured, and the other that they were killed, by the use of these waters. Such contrary decisions, so disreputable to physi cians, and so perplexing to the sick, could never have happened after so long a trial, if a very small part of those, whose practice had afforded them frequent opportunities of observing the effects of Bath waters, had told the public what in their judgment was to be hoped or feared from them. It is probable that in some cases it would have been almost unanimously determined they do good: in others, that they do no harm, though it might be doubtful whether they be of much use: in a third sort they would be generally condemned: and in a fourth class of diseases, some might judge them to be beneficial, and others detrimental. William Heberden, Commentaries on the History and Cure of Diseases, 1802 From Perspectives in Biology and Medicine, Summer, 1976
The specular microscope was invented by Maurice 1 and modified for clinical use by Bourne and Kaufman. 2 Its clinical applications have so far documented sev eral findings regarding the status of the corneal endothelial population both be fore and after anterior segment proce dures. Endothelial cell density can be from 1,600 to 4,000 cells/mm 2 in unoperated eyes. 2 Comparisons of preoperative and postoperative central corneal cell counts have shown a 10 to 15% aver age cell loss after intracapsular cataract extraction. 3 Central cell losses averaging 35% were demonstrated in counts taken in lens implant cases done by open sky implantation techniques 4 and 14% when implanted with deep chamber closed-eye techniques. 5 A 67% cell loss was noted after traumatic lens implantation, as com pared to a 16% loss with atraumatic im plantation. 6 Phacoemulsification has been reported to cause a 50% increase in cell loss over intracapsular extraction. 7 Based on a small series, Blackwell, Gfavenstein, and Kaufman 8 identified a uniform distribution of cell density com paring peripheral and central areas of the cornea in both preoperative and postoper ative eyes, thus postulating central counts as representative of the entire cornea. 8 We report herein a study on a large series of postoperative corneas to determine whether a central count was a true indica tion of the endothelial cell population in all areas of the cornea. From the Jules Stein Eye Institute, UCLA and Santa Monica Hospital Eye Laboratory, Santa Monica, California. This study was supported by a grant from Heyer-Schulte Medical Optics Center. , Reprint requests to Kenneth J. Hoffer, M.D., 2001 Santa Monica Blvd., 460-W, Santa Monica, CA 90404. 344
M.D.
California METHODS
All subjects in this study were random ly selected from patients referred to us for routine postoperative central endothelial counts. A Syber endothelial specular mi croscope was used for all endothelial photography. 2 To obtain photographs in the superior and inferior cornea that would be reproducible, a system of posi tioning was devised. A simple fixation light device from a slit lamp was attached to the chin rest assembly of the endotheli al camera. This was used to aid the pa tient in maintaining the appropriate gaze. While the endothelium was observed through the sighting of the camera, the patient was instructed to look up (or down) until, with proper camera cone adjustment, the endothelium could no longer be seen (exceeding peripheral limit of photography). The fixation device was then moved slowly in the opposite direc tion until a clear image of endothelial cells could be photographed. Assurance of position was checked by intermittent gross observations of the eye. This posi tion was found to be approximately 2 mm from the corneoscleral limbus superiorly and inferiorly. The fixation device used by Blackwell, Gravenstein, and Kaufman 8 was not available or used in this study. Six to ten photographs were taken in each area and three of the best from each area were selected for printing and counting. Counting was performed by totalling the number of all whole and partial cells touching one horizontal and one vertical edge of the print. The mean of the three photographs of each set was multiplied by our magnification factor (x 74), arrived at by comparison with an initial photo graph of a micrometer scale, to arrive at the cell density in cells per square milli-
AMERICAN JOURNAL O F OPHTHALMOLOGY 87:344-349, 1979
VOL. 87, NO. 3
VERTICAL E N D O T H E L I A L C E L L DISPARITY
meter. A coding of each photograph was used to insure accurate documentation. One eye each of 59 patients ranging in age from 46 to 89 years, average age 72 years, was photographed in this manner. Thirty-four patients underwent phacoemulsification and 31 of these received a lens implant. Twenty-five patients under went intracapsular cataract extraction and 20 of these received lens implant. In all cases phacoemulsification was performed through a 12 o'clock superior incision (photography was performed in this area). These procedures were performed by var ious surgeons using varying techniques and lens styles. A separate series of 23 normal control (unoperated) eyes were photographed in a similar manner. The 23 patients ranged in age from 21 to 85 years; the average age was 53 years. RESULTS
Vertical cell disparity counts performed on the first six normal control eyes sub stantiated the uniform population shown by Kaufman. 8,9 Figure 1 shows the uni form vertical density in an eye with a high cell count; Figure 2 shows uniform verti cal density in an eye with a low cell count. An evaluation of the vertical counts of all 23 control eyes revealed no trend of disparity between the superior and inferior regions (Table 1). Vertical cell disparity is defined as the percentage
345
change in cell density from the inferior count to the superior count I-S
I.
The
vertical cell disparity of the control eyes ranged from - 3 5 % to +35% with a mean of - 4 % (Table 1). The results of the first six postoperative patients indicated a def inite vertical disparity in cell density be tween the superior and inferior cornea. 9 Figure 3 shows the cell populations of a recently operated eye (two weeks); Figure 4 shows an eye operated on three years before examination. Table 2 shows the cell counts of the 59 subject eyes. The vertical cell disparity in this group ranged from —38% to +38% with a mean of +40%, compared to the mean of —4% of the control group. Of the subject eyes, 97% showed a positive vertical cell dis parity, as compared to 43% in the control group. The disparity between the superi or and inferior cornea did not depend on the interval between surgery and photog raphy. Vertical disparity was noted in eyes with low postoperative cell counts (Fig. 5). In the subject group, 52 eyes (87%) showed a definite superior-inferior gradi ent in which the highest cell count was inferior and the lowest was superior. An other six eyes (10%) showed higher cen tral than inferior cell counts, but in these cases the superior count was still the lowest of the three areas. Only one eye (2%) showed a higher cell count in the
SUPERIOR 2787
j^-W^..^' ■■vLk
CENTRA! 2664
.»%•. * j p w INfERIOR 234'J
Fig. 1 (Hoffer). Vertical cell counts on a preoperative normal control eye in a 61-year-old patient.
INFERIOR 715
Fig. 2 (Hoffer). Low vertical counts on a preoperative normal control eye in an 84-year-old patient.
346
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH, 1979
TABLE 1 V E R T I C A L C E L L C O U N T S , C O N T R O L S : C E L L DENSITY ( C E L L S / M M 2 ±
Patient No.
Age (yrs)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
26 21 40 21 79 27 59 84 81 72 61 84 72 73 66 66 21 21 85 22 22 46. 73
Mean
SD*)
VCD
Superior
Central
Inferior
VCM
(%)
2688 : 151 2837 : 229 2 4 6 7 : : 178 2639 : 85 2442 210 3577 : 143 1727 : 178 2664 : 201 691 : 34 2491 : 170 3009 : 200 592 : 58 1579 : 121 2960: 204 2787 : 210 2319: 158 3330 : 232 2935 : 213 1899 : 187 3330 : 179 3651 : 235 2590: 187 2245: 150 2451
2368 144 2738 187 2516 203 2220: 165 2565 142 3059: 99 1950: 110 2343 : 221 962 53 2664 : 200 2319 ; 191 765 : 78 1850 : 113 2171 : 175 2664: 201 2245 : 187 3083 : 223 3281 : 340 1776 : 187 3281 : 225 3305 : 243 2146 : 178 2294 : 199 2328
2738 : 168 2615: 200 2294 : 164 2417 : 178 197 2491 2960 : 203 2442 : 194 2541 : 210 1061 : 75 2615: 194 2713 : 176 715 : 54 1603 : 111 2516 : 187 2343 : 200 2245 : 191 2960 : 127 3182 : 178 2146 : 161 3108 : 213 2837 : 198 1924 : 100 2368 : 186 2360
2598 2730 2426 2425 2499 3199 2040 2516 905 2590 2680 691 1677 2549 2598 2270 3124 3133 1940 3240 3264 2220 2302 2388
2 - 8 2 -21 29 - 5 35 5 -11 17 2 -18 -19 - 3 -13 8 12 - 1 -29 -35 5 - 4
*VCM designates vertical cell mean; VCD, vertical cell disparity (difference between superior and inferior count) I-S I
superior area. Similar findings were first noted by J. Flaxen (personal communica tion, 1978) in studies of postcataract ca daver corneas by direct regional counting of cells by light microscopy. A comparison of the means of the re gional densities was made between the
INFfRIOH 2514
Fig. 3 (Hoffer). Vertical cell disparity (45%) in an eye of a 61-year-old patient two weeks after phacoemulsification and lens implant.
controls and subjects (Fig. 6). A 2 3 % infe rior cell loss was evident compared to twice that (46%) in the superior area (Table 3). The central cell loss (38%) compared well with previous studies 4 as well as to the vertical cell mean loss (39%) of averaging all three areas (Table 3).
INftRIO* H55
Fig. 4 (Hoffer). Vertical cell disparity (36%) in an eye of a 46-year-old patient three years after phacoemulsification and lens implant.
TABLE 2 V E R T I C A L C E L L C O U N T S , SUBJECTS: C E L L D E N S I T Y ( C E L L S / M M 2 ) ±
atient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Mear i
Age (yrs)
Surgery
47 47 61 57 80 64 69 46 66 46 73 75 49 52 52 70 86 61 64 63 74 74 64 77 77 46 81 79 57 61 61 76 78 69 72 62 75 75 75 80 58 65 77 70 77 81 77 89 74 74 68 75 73 73 79 79 55 65 58
PKE PKE PKE ICCE ICCE ICCE ICCE ICCE PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL PKE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL ICCE/IOL
Post-Operative
Superior
Central
SD*
Inferior
VCM
VCD
(%) 3 mos 15 mos 4V2 yrs 4 yrs 2 yrs 7 yrs 8V2 yrs 4 mos 20 mos 3 yrs 5 yrs 4 mos 4 mos 2 mos 2 yrs 2 yrs 3 yrs 2 wks 3 yrs 2 mos 3V2 yrs 6 mos 1 wk 4 mos 1 mo 3 yrs 3 yrs 2 yrs 3 mos 2 mos 3 yrs 3 mos 3 mos 2 yrs 2 mos 2 mos 2 yrs 9 mos 2 yrs 4 mos 7 mos 3 mos. 4 mos 18 mos 4 mos 5 mos 3 mos 1V2 yrs 2 yrs 3 yrs 4 yrs 3 mos 4 yrs 4 yrs 3 mos 2 mos 2 mos 4 mos 3 mos
1776 1159 1233 937 1480 617 567 1258 1233 1036 1159 1209 740 1233 1924 789 789 1381 592 1307 888 1209 1776 962 1406 937 616 666 1505 1258 765 1061 888 789 1554 1110 691 937 666 691 1554 1110 1776 1455 1431 740 1110 493 666 1357 962 1036 814 839 1924 1702 1036 1061 666 1093
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± + ±
187 219 152 87 200 53 21 87 152 121 200 127 86 216 187 84 21 126 49 28 11 201 186 36 99 102 48 110 176 144 187 200 106 48 212 165 87 105 49 110 110 87 128 210 87 100 121 81 38 143 42 100 96 152 171 153 129 87 101
2467 ± 243 1603 ± 145 2146 ± 161 1554 ± 102 1603 ± 164 592 ± 83 740 ± 56 1085 ± 122 2097 ± 201 1455 ± 187 1135 ± 176 1727 ± 145 1209 ± 123 1875 ± 184 1776 ± 191 691 ± 100 1061 ± 201 1850 ± 187 641 ± 24 1751 ± 121 888 ± 87 1751 ± 124 2121 ± 200 1307 ± 113 2097 ± 187 1282 ± 124 740 :± 93 666 ± 46 1899 ± 119 1924 ± 186 1184 ± 124 1800 ± 136 1455 ± 200 1036 ± 147 1924 ± 200 Guttatat 1061 ± 121 1381 ± 138 839 ± 146 863 ± 27 1998 ± 210 2220 ± 187 2023 ± 302 2097 ± 144 2171 ± 169 937 ± 110 2664 ± 203 567 ± 46 937 ± 119 1727 ± 287 937 ± 101 1875 ± 186 715 ± 110 863 ± 147 2072 ± 128 1061 ± 200 1085 ± 143 2294 ± 187 789 ± 46 1610
2985 ± 2763 ± 2097 ± 2615 ± 2368 ± 937 ± 937 ± 2245 ± 2467 ± 1653 ± 1283 ± 1653 ± 2343 ± 2195 ± 2541 ± 1061 ± 962 ± 2516 ± 913 ± 2072 ± 1209 ± 1949 ± 2269 ± 2615 ± 2171 ± 1455 ± 863 ± 987 ± 2368 ± 1949 ± 1307 ± 1776 ± 2393 ± 1307 ± 2294 ± 1825 ± 1307 ± 1831 ± 1258 ± 1159 ± 2171 ± 2491 ± 2689± 2442 ± 2639 ± 1899 ± 2442 ± 617 ± 1209 ± 2146 ± 1159 ± 1307 ± 666 ± 1700 ± 2368 ± 1431 ± 2097 ± 2491 ± 913 ± 1819
114 129 230 315 186 111 87 128 138 200 46 118 213 196 202 87 58 200 161 212 100 128 302 229 144 201 110 86 245 186 0 150 198 102 210 187 113 129 147 55 187 301 506 127 210 187 164 127 145 183 111 119 42 0 203 89 200 146 121
2409 1842 1825 1702 1817 715 748 1529 1932 1381 1192 1530 1431 1768 2080 847 937 1916 715 1710 995 1636 2055 1628 1891 1225 740 773 1924 1710 1085 1546 1579 1044 1924 1468 1020 1233 921 904 1908 1940 2163 1998 2080 1192 2072 559 937 1743 1019 1406 731 1134 2121 1398 1406 1950 790 1507
41 58 43 60 37 39 52 44 50 37 12 30 68 44 44 35 26 45 35 37 27 38 22 63 35 36 29 33 36 35 41 41 63 40 32 39 47 32 47 40 28 55 34 40 46 61 58 20 45 37 19 45 -18 51 19 -38 51 57 27 40
*PKE designates phacoemulsification; ICCE, intracapsular cataract extraction, IOL, intraocular lens; VCM, vertical cell mean; VCD, vertical cell disparity (difference between superior and inferior count) fl-S"l. f Unable to count. ,
348
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH, 1979
TABLE 3 C E L L LOSS COMPARISON O F C O N T R O L AND SUBJECT G R O U P S *
Means
INfERIOR 2393
Fig. 5 (Hoffer). Vertical cell disparity (63%) in an eye of a 78-year-old patient with large postoperative cell loss three months after phacoemulsiflcation and lens implant.
Controls Subjects Cell loss,
%
Superior Counts
Central Counts
Inferior Counts
VCM
2451 1094 46
2328 1452 38
2360 1818 23
2388 1455 39
*VCM designates vertical cell mean.
taining central and not peripheral counts when comparing preoperative and post operative central cell counts. Evaluating cell populations in all areas of the cornea is important before performing secondary procedures on previously operated eyes. An inferior or temporal-nasal approach may be safer to a cornea with low cell density superiorly. Once a damaged area of the cornea is covered by endothelial cells the stimulus for cell movement stops until cell mem brane contact is lost by dying cells or further damage.
DISCUSSION
These data indicate a need to broaden our view when estimating endothelial cell losses. Endothelial damage is much high er in the superior area of the cornea where the incision is made and most manipula tions are performed. The inferior area of the cornea is the least affected by intra ocular procedures. Central counts are more a mathematical average of cell density than an indicator of overall uniform density, and time does not appreciably alter the vertical cell disparity caused by surgical trauma. Only long range pro SUMMARY spective studies of postoperative eyes will Endothelial cell counts were performed conclusively document the lack of uni postoperatively in superior, central, and form density healing after surgical trau inferior areas of the cornea in 59 patients. ma. No regional differences were found in a Diligence must be maintained in obseries of 23 preoperative control cataract eyes. A definite, large density disparity was noted in 58 of the 59 postoperative corneas studied. Disparity was high nine years as well as two weeks postopera tively. These data indicated the necessity for accuracy of positioning in postopera tive comparison studies and the necessity for regional cell counts before secondary surgical procedures. MEAN CELLS PER M M ;
2500 -
2000 -
1500 -
INFERIOR
CENTRAL CORNEAL
SUPERIOR
LOCATION
Fig. 6 (Hoffer), Graphic comparison of mean inferior central and superior cell counts in the control and subject series.
ACKNOWLEDGMENT
Gregory W. Phillippi provided the vertical cell studies and developed the application of the tech nique.
VOL. 87, N O . 3
VERTICAL E N D O T H E L I A L C E L L DISPARITY
REFERENCES 1. Maurice, D. M.: Cellular membrane activity in the corneal endothelium of the intact eye. Experientia. 24:1094, 1968. 2. Bourne, W. M., and Kaufman, H. E.: Specular microscopy of human corneal endothelium in vivo. Am. J. Ophthalmol. 81:319, 1976. 3. : Cataract extraction and the corneal en dothelium. Am. J. Ophthalmol. 82:44, 1976. 4. Forstot, S. L., Blackwell, W. L., and Jaffe, N. S.: Effect of intraocular lens implantation on the corneal endothelium. Trans. Am. Acad. Ophthalmol. Otolaryngol. 83:195, 1977. 5. Hirst, L. W., Snip, R. C , Stark, W. J., and Maumenee, E.: Quantitative corneal endothelial
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evaluation in intraocular implantation and cataract surgery. Am. J. Ophthalmol. 84:775, 1977. 6. Sugar, J., Mitchelson, J., and Kraff, M. C : Endothelial trauma and cell loss from intraocular lens insertion. Arch. Ophthalmol. 96:449, 1978. 7. Sugar, J., Mitchelson, J., and Kraff, M. C : The effect of phacoemulsification on corneal endothelial cell density, Arch. Ophthalmol. 96:446, 1978. 8. Blackwell, W. L., Gravenstein, N., and Kauf man, H. E.: Comparison of central corneal endothe lial cell numbers with peripheral areas. Am. J. Ophthalmol. 84:473, 1977. 9. Hoffer, K. J., and Phillippi, G.: A cell mem brane theory of endothelial repair and vertical cell loss after cataract surgery. Am. Intra-Ocular Implant Soc. J. 4:18, 1978.
O P H T H A L M I C MINIATURE
. . . the uncertainty, under which we still remain, in regard to the virtue of the waters of Bath. Few medicines have been more repeatedly tried under the inspection of such numerous and able judges; and yet we have had in the present age a dispute between those who by their experience and sagacity were best qualified to decide this question, in which one side asserted that paralytic patients were cured, and the other that they were killed, by the use of these waters. Such contrary decisions, so disreputable to physi cians, and so perplexing to the sick, could never have happened after so long a trial, if a very small part of those, whose practice had afforded them frequent opportunities of observing the effects of Bath waters, had told the public what in their judgment was to be hoped or feared from them. It is probable that in some cases it would have been almost unanimously determined they do good: in others, that they do no harm, though it might be doubtful whether they be of much use: in a third sort they would be generally condemned: and in a fourth class of diseases, some might judge them to be beneficial, and others detrimental. William Heberden, Commentaries on the History and Cure of Diseases, 1802 From Perspectives in Biology and Medicine, Summer, 1976
