The Corneal Endothelium After Laser Therapy for Glaucoma Christopher Thoming, M.D., E. Michael Van Buskirk, M.D., and John R. Samples, M.D.
Using computer assisted morphologic analy sis of central corneal endothelial specular mi crographs, we prospectively examined the ef fects of glaucoma laser procedures on the corneal endothelium. Argon laser trabeculoplasty was performed in 22 eyes of 17 patients. Argon laser iridotomy was performed in 14 eyes of seven patients. Untreated fellow eyes in ten patients undergoing laser trabeculoplasty were used as controls. After one year, no statistically significant difference in cell area, percent hexagonal cells, or shape factor was observed. Our results suggest that argon laser procedures do not pose any long-term hazard to the corneal endothelium. ARGON LASER trabeculoplasty and argon laser
iridotomy are used to treat open-angle 1 3 and pupillary block4"7 glaucomas, respectively. Al though these procedures usually produce no clinically recognized adverse sequelae, many patients experience a transient increase in intra ocular pressure, mild anterior uveitis, and fo cal corneal burns. Corneal damage may result from abrasions, opacities, and both epithelial and endothelial burns. 6 ' 811 With the current practice of treating anterior trabecular meshwork in laser trabeculoplasty some burns may occasionally stray onto peripheral cornea. The long-term effects of these procedures on the cornea, specifically the corneal endothelium, are not entirely understood. Previous studies have focused on short-term alterations, em-
Accepted for publication Dec. 29, 1986. From the Department of Ophthalmology, Oregon Health Sciences University, Portland, Oregon. This study was supported in part by Research to Prevent Blindness, Inc. Reprint requests to John R. Samples, M.D., Depart ment of Ophthalmology, Oregon Health Sciences Uni versity, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97201.
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ploying cell density measurements from specu lar micrographs as the index of endothelial status. More sensitive, quantitative indices evaluating factors such as cell shape, area, and percent of hexagonal cells of the endothelium have been devised by Matsuda and coworke r s !2-i5 YJe r e p o r t the results of a one-year follow-up study using detailed quantitative morphometric analysis of corneal specular pho tomicrographs after argon laser trabeculoplasty and iridotomy.
Subjects and Methods Twenty-four patients were enrolled in this study. Seventeen patients (22 eyes) with openangle glaucoma underwent laser trabeculo plasty. Seven patients (14 eyes) underwent laser iridotomy. All procedures were per formed at our institution by one of two of us (E.M.V.B. or J.R.S.). Patients were excluded from the study if they had a history of eye trauma, corneal disease, diabetes mellitus, in traocular surgery, or laser therapy. Because acute rises in intraocular pressure can damage the corneal endothelium, patients who devel oped an acute intraocular pressure rise during the follow-up period were excluded from the analysis. Twenty-two eyes (17 patients) were treated with laser trabeculoplasty. Five patients were treated bilaterally. Ten untreated eyes in these patients were used as controls. One treatment eye and one control eye were excluded because of poor photographic results. Standard laser trabeculoplasty techniques were employed throughout the study. A total of 3.5 to 9.0 J of energy was delivered to the anterior nonpigmented portion of the trabecular meshwork of the treated eyes. All eyes were treated for 360 degrees with between 70 and 100 burns (mean, 88 burns). A 0.1-se«ond shutter speed and
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50-u.m spot size were used. Antiglaucomatous medications were continued after treatment with close monitoring of the intraocular pres sure for at least six hours. After treatment topical prednisolone acetate 1% was prescribed for one week, every two hours on the first day then three times daily. Thirteen eyes (seven patients) were treated with laser iridotomy. After topical miotic and anesthetic were administered, laser energy was generally delivered in two phases. Preparatory burns using between five and eight applica tions of 200 to 500 mW of power for 0.1 second and a 200-u.m spot size were followed by pene tration burns of 500 to 1,200 mW for 0.2 second. Thus, in treated eyes, 1.9 to 12.7 J of energy were delivered to the iris until a satisfactory iridotomy was obtained. Topical prednisolone acetate was prescribed after therapy. Specular micrographs were obtained before and nine to 17 months after laser treatment. Two specular microscopes were used, but each eye was examined with the same instrument before treatment and throughout the follow-up period. Ten photomicrographs were taken of each central cornea. One was selected primari ly for sharp focus and clarity of endothelial cell borders. This print was enlarged approximate ly 400 times. Fifty cells were randomly selected and numbered sequentially to prevent duplica tion during analysis. A digitizer and analysis software were then used to determine morphometric features including cell area, cell perime ter, and shape factor (4 x A/P2, where A is the cell area and P is the cell perimeter). Shape factor14 is a dimensionless index describing how closely a given shape approximates a circle, which has a shape factor of 1.00. (A straight line has a shape factor value of 0.00, and a
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TABLE 1 PATIENT DATA
CONTROL (N=10)
Follow-up period (mos) Mean 11.6 Range 9 to 13 Age (yrs) Mean 69.2 Range 43 to 94 Preoperative intraocular pressure (mm Hg) Mean 23.2 Range 16 to 33
LASER
LASER
TRABECULOPLASTY (N=22)
IRIDOTOMY
13.2 8 to 23
10.8 9 to 17
73.8 56 to 84
71.4 43 to 84
27.4 21 to 54
25.6 12to30
(N=13)
perfect hexagon has a value of 0.907.) Percent hexagonal cells was determined by visual in spection of the randomly selected cells. Statisti cal analysis was carried out using Student's f-test.
Results The mean preoperative intraocular pressure was higher for eyes that had undergone laser trabeculoplasty and laser iridotomy than for the control eyes (Table 1). Pretreatment cell morphometric features were identical between all groups (Table 2). Similarly, at the one-year follow-up visit, no significant difference in ei ther cell density, percent hexagonality, or shape factor was detectable. When treatment
TABLE 2 ENDOTHELIAL MORPHOMETRIC FEATURES BEFORE AND AFTER LASER THERAPY (MEAN ± S.E.M.)
CONTROL PREOPERATIVE
Cell area (mm2 x 10") Cell density (cells/mm2) Hexagonality (%) Shape factor (4 x A/P2)
POSTOPERATIVE
LASER TRABECULOPLASTY PREOPERATIVE
POSTOPERATIVE
LASER IRIDOTOMY PREOPERATIVE
POSTOPERATIVE
4.577 ± 0.341
4.269 ± 0.273
4.448 ± 0.133
4.248 ± 0.181
4.584 ± 0.138
4.678 ± 0.122
2,185 ± 152 70.40 ± 5.9
2,342 ± 140 68.80 ± 8.01
2,248 ± 65 66.27 ± 9.08
2,354 ± 161 66.64 + 8.03
2,181 ± 63 61.54 ± 6.33
2,138 ± 55 64.15 ± 7.00
0.8681 ± 0.003
0.8741 ± 0.007
0.8696 ± 0.003
0.8681 ± 0.004
0.8739 ± 0.003
0.8718 ± 0.003
520
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Laser Trabeculoplasty
Laser Iridotomy
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Fig. 1 (Thoming, Van Buskirk, and Samples). His togram showing central corneal endothelial cell den sity (± S.E.M.) before and after laser treatment, as compared to control. g r o u p s w e r e c o m p a r e d w i t h control eyes a n d also a g a i n s t p r e t r e a t m e n t v a l u e s in the s a m e e y e s , n o statistical difference in a n y feature w a s observed. Histograms depicting results both before a n d after laser t r e a t m e n t s h o w n o signif icant c h a n g e in m e a n cell area, p e r c e n t h e x a g o nal cells, a n d s h a p e factor respectively (Figs. 1-3).
Control Laser Laser Iridotomy Trabeculoplasty Fig. 2 (Thoming, Van Buskirk, and Sam pies). Histogram showing percent of central corneal endothelial hexagonal cells (± S. E.M.) before and after laser treatment, as compared to control. corneal disease, 1 4 1 6 a n d attacks of a c u t e in creased intraocular pressure have been shown to c a u s e significant corneal e n d o t h e l i a l cell loss. 1 7
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Discussion X
The c u r r e n t t r e a t m e n t of the a n t e r i o r p o r t i o n of t h e t r a b e c u l u m d u r i n g laser t r a b e c u l o p l a s t y has raised the q u e s t i o n of possible l o n g - t e r m m a n i f e s t a t i o n s of corneal e n d o t h e l i a l injury from g l a u c o m a laser p r o c e d u r e s . D e s p i t e so p h i s t i c a t e d a n d detailed q u a n t i t a t i v e a n a l y s i s , n e i t h e r laser i r i d o t o m y n o r laser t r a b e c u l o plasty p r o d u c e d a n y m e a s u r a b l e d e l e t e r i o u s effect o n t h e corneal e n d o t h e l i u m d u r i n g the first p o s t o p e r a t i v e year. A n u m b e r of corneal c o m p l i c a t i o n s of t h e s e p r o c e d u r e s h a v e b e e n documented including opacities, burns, e d e m a , a n d external abrasions. 6 ' 8 1 1 Severe cor neal d e c o m p e n s a t i o n h a s b e e n o b s e r v e d after laser t r e a t m e n t in p a t i e n t s w i t h u n d e r l y i n g
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Laser Laser Control Trabeculoplasty iridotomy Fig. 3 (Thoming, Van Buskirk, and Samples). His to togram showing central corneal endothelial cell shape factor values (± S.E.M.) before and after laser treatment, as compared to control.
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Other investigators have also demonstrated no change in the corneal endothelium at vari ous times after laser treatment. Hirst and coworkers 18 reported no significant change in endothelial status in cynomolgus monkeys one month after laser iridotomy and panretinal photocoagulation. Similarly, Smith and Whitted 19 observed no notable effect of laser iridotomy on endothelial cell density in hu mans during a follow-up period of up to 41 weeks. Traverso and colleagues 20 investigated endothelial status for four months after laser trabeculoplasty and found no change in cell density. Additionally, Schrems, Belcher, and Thomlinson 21 documented no significant de crease in central corneal endothelial cell densi ty 12 weeks after Nd:YAG trabeculoplasty or iridectomy.
is also not surprising since this factor has been found to dynamically parallel the state of the endothelial changes after intraocular surgery. 13 Matsuda and colleagues 13 noted an initial de cline in frequency of hexagonal cells two to four weeks after either cataract extraction or pene trating keratoplasty. However, by 24 weeks the percent hexagonality had returned to preoperative values. Thus, if there had been a decline in hexagonality because of laser damage, we may not have detected it because of the longer follow-up period. Our study demonstrates that argon laser iridotomy and laser trabeculoplasty does not compromise the normal corneal endo thelium after one year.
Hong, Kitazawa, and Tanishima, 22 however, showed an increase in mean endothelial cell size three months after laser iridotomy and six months after laser trabeculoplasty. Additional ly, the degree of endothelial cell loss was sig nificantly correlated with the amount of laser energy delivered during laser iridotomy. In their study, 4.8 to 27.8 J were delivered to iridotomy eyes, as compared to 1.9 to 12.7 J (mean, 6.1 J) in the present study. For laser trabeculoplasty, the total energy delivered in this series ranged from 3.5 to 9.0 J. This is far below that used by Hong, Kitazawa, and Tanishima (18.4 to 21.4 J). That our patients received less total energy to the trabeculum or iris may account for the preservation of normal endothelium. Direct laser insult to the cornea in animal models has been shown to be damag ing to endothelial cells. 23 This underscores the need for operative protocols that provide opti mal therapeutic effect while using the least amount of laser energy possible.
References
In a series of recent reports 1216 Matsuda and coworkers have utilized, in addition to endo thelial cell density, quantitative measurements of endothelial cell structure and pattern includ ing coefficient of variation in cell size, frequen cy of hexagonal cells, and figure coefficient. Their results suggest that these factors are a more sensitive indicator of endothelial insult than changes in cell density. In the present study we also analyzed figure coefficient (shape factor) and frequency of hexagonal cells to assay changes in the endothelium after laser trabeculoplasty or laser iridotomy. We did not observe any detectable change after one year in patients with previously healthy corneas. The finding of an unchanged percentage of hexago nal cells nine to 17 months after laser treatment
1. Wise, J. B., and Wittier, S. L.: Argon laser ther apy for open-angle glaucoma. A pilot study. Arch. Ophthalmol. 97:319, 1979. 2. Wise, J. B.: Long term control of adult openangle glaucoma by argon laser treatment. Ophthal mology 88:197, 1981. 3. Schwartz, A. L., and Kopelman, J.: Four-year experience with argon-laser trabecular surgery in uncontrolled open-angle glaucoma. Ophthalmology 90:771, 1983. 4. Khuri, C. H.: Argon laser iridectomies. Am. J. Ophthalmol. 76:490, 1973. 5. Abraham, R. K., and Miller, G. L.: Outpatient argon laser iridectomy for angle closure glaucoma. A two year study. Trans. Am. Acad. Ophthalmol. Otolaryngol. 79:529, 1975. 6. Podos, S. M., Kels, B. D., Moss, A. P., Ritch, R., and Anders, M. D.: Continuous wave argon laser iridectomy in angle-closure glaucoma. Am. J. Oph thalmol. 88:836, 1979. 7. Robin, A. L., and Pollack, I. P.: Argon laser peripheral iridotomies in the treatment of primary angle-closure glaucoma. Long term follow-up. Arch. Ophthalmol. 100:919, 1982. 8. Hoskins, D. M., Jr., Hetherington, J., Jr., Minckler, D. S., Lieberman, M. F., and Shaffer, R. N.: Complications of laser trabeculoplasty. Oph thalmology 90:796, 1983. 9. Pollack, I. P.: Use of argon laser to produce iridotomies. Trans. Am. Ophthalmol. Soc. 77:674, 1979. 10. Ritch, R., and Podos, S. M.: Argon laser treat ment of angle closure glaucoma. Perspect. Ophthal mol. 4:129, 1980. 11. Quigley, H. A.: Long term follow-up of laser iridotomy. Ophthalmology 88:218, 1981. 12. Matsuda, M., Suda, T., and Manabe, R.: Quantitative analysis of endothelial mosaic pattern changes in anterior keratoconus. Am. J. Ophthalmol. 98:43, 1984.
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13. Matsuda, M., Suda, T., and Manabe, R.: Serial alterations in endothelial cell shape and pattern after intraocular surgery. Am. J. Ophthalmol. 98:313, 1984. 14. Schultz, R. O., Matsuda, M., Yee, R. W., Edelhauser, H. F., and Schultz, K. J.: Corneal en dothelial changes in type I and type II diabetes mellitus. Am. J. Ophthalmol. 98:401, 1984. 15. Karai, I., Matsumura, S., Takise, S., Horiguchi, S., and Matsuda, M.: Morphological change in the corneal endothelium due to ultraviolet radiation in welders. Br. J. Ophthalmol. 68:544, 1984. 16. Mackay, C. J., Koester, C. J., and Campbell, C. J.: The corneal endothelium following photocoagulation. Induced decompensation. Ann. Ophthal mol. 15:346, 1983. 17. Bigar, F., and Witmer, R.: Corneal endothelial changes in primary acute angle-closure glaucoma. Ophthalmology 89:596, 1982. 18. Hirst, L. W., Robin, A. L., Sherman, S., Green, W. R., D'Anna, S., and Dunkelburger, G.:
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Corneal endothelial changes after argon laser iridotomy and panretinal photocoagulation. Am. J. Oph thalmol. 93:473, 1982. 19. Smith, J., and Whitted, P.: Corneal endothelial changes after argon laser iridotomy. Am. J. Ophthal mol. 98:153, 1982. 20. Traverso, C , Cohen, J. E., Groden, L. R., Cassel, G. H., Laibson, P. R., and Spaeth, G. L.: Central corneal endothelial cell density after argon laser trabeculoplasty. Arch. Ophthalmol. 102:1322, 1984. 21. Schrems, W., Belcher, C. D., and Thomlinson, C. P.: Changes in the human control corneal endo thelium after neodymium:YAG laser surgery. Oph thalmic Laser Ther. 1:143, 1986. 22. Hong, C , Kitazawa, Y., and Tanishima, H.: Influence of argon laser treatment of glaucoma on corneal endothelium. Jpn. J. Ophthalmol. 27:567, 1983. 23. Nash, J. P., Wickham, M. G., and Binder, P. S.: Corneal damage following focal laser interven tion. Exp. Eye Res. 26:641, 1978.