Modification of Corneal
Curvature Following Radial Keratotomy in Primates
DOUGLAS STEEL, MD, JAMES V. JESTER, PhD, JAMES SALZ, MD, RICHARD A. VILLASENOR, MD, JOHN S. LEE, MD, DAVID J. SCHANZLIN, MD, RONALD E. SMITH, MD
Abstract: Radial keratotomy was performed on six stumptail monkey eyes (Macaca speciosa) and 22 owl monkey eyes (Aotus trivirgotus). Changes in keratometry, pachometry, specular microscopy, and tonometry have been studied postoperatively for three to six months. Sixteen radial incisions in stumptail monkey eyes resulted in a significant mean corneal flattening of 2.75 diopters (P < 0.005). This effect was stable with a mean 2.50 diopters flattening remaining six months after surgery. Sixteen radial incisions in ten owl monkey eyes resulted in a much greater short-term effect, with a mean 10.50 diopters of flattening present at two weeks postoperatively. This flattening deteriorated over the observation period, and no significant effect was noted three months after surgery. A comparison of 8 vs 16 incisions on owl monkey eyes demonstrated that these two procedures are equally effective in initially flattening the cornea. Compl ications and side effects encountered included perforations, irregular astigmatism, corneal neovascularization, transitory increase in pachometry, and decrease in central corneal endothelial cell density in isolated cases. [Key words: cornea, corneal curvature, primates, radial keratotomy, refractive surgery.] Ophthalmology 88: 747-754,1981
Laboratory animal studies are an important first step in the development of most surgical techniques. Safety and efficacy of new procedures, including complications, variations in technique, and histopathologic alterations in affected tissues, etc, may be determined in animals prior to human trials. However, radial keratotomy is rapidly evolving in this country despite
an almost total lack of reported animal studies. 1 ,2 This paper reports our results following radial keratotomy in subhuman primates.
MATERIAL AND METHODS SELECTION OF PRIMATE
From the Department of Ophthalmology, University of Southern California and Estelle Doheny' Eye Foundation, Los Angeles, CalIfornia. Presented at the Eighty-fifth Annual Meeting of the American Academy of Ophthalmology Meeting Chicago, November 2-7, 1980. Supported in part by NIH grant EY-03562-01. Reprint requests to Douglas Steel, MD, 1355 San Pablo Street, Los Angeles, CA 90033. 0161-6420/8110800/0747/$00.90
© American Academy of Ophthalmology
Macaca speciosa (stumptail) and Aotus trivirgotus (owl monkey) were studied in an attempt to define various surgical parameters and to identify an appropriate model. A total of six stumptail and 22 owl monkey eyes received radial incisions. All animals were initially sedated with Ketamine, Acepromazine, and Atropine (1: 1: 1) intramuscularly prior to testing and surgery. Stumptail monkeys required deeper anesthesia with intravenous sodium pentobarbitol. 747
OPHTHALMOLOGY. AUGUST 1981 • VOLUME 88 • NUMBER 8
STUDY PARAMETERS
Several parameters were evaluated preoperatively and at two weeks, four weeks, six weeks, two months, three months, four months, five months, and six months postoperatively in most animals. All observations were made by a trained nonsurgeon observer. Corneal curvature (keratome try). The Terry keratometer attached to the Zeiss Opmi 6 operating microscope was used for all evaluations in the pre- and post-operative periods. Eyelids of the primate were held open manually without pressure on the globe itself, and the cornea moistened with a minimal amount of balanced salt solution. Readings were taken according to standard Terry techniques. The same observer (not the surgeon) performed examinations in the pre- and the post-operative period without knowledge of the previous readings. Three separate keratometry readings were taken at each time interval, and the values averaged and rounded to the nearest quarter diopter. Corneal thickness. The Heyer Schulte specular microscope was utilized both for endothelial cell counting and corneal thickness measurements. Using the standard technique of specular microscopy, the corneal thickness was noted as a digital read-out on the instrument. Three pachometry readings were made at each follow-up period and the average recorded. (Previous studies in our laboratories evaluating this method of measuring corneal thickness have revealed it to be reproducible and accurate. 3) Specular microscopy. The Heyer Schulte specular microscope was used with an experienced technician performing all endothelial cell photographs and counts according to standard techniques. It was necessary to perform this technique with the monkey in a reclining position. A minimum of 18 photographs were taken of each eye with the best five picked for counting. Axial length determination. The Kretz A Scan unit was used to determine axial length in the first five cases. However, there was no observable difference in axial length in the postoperative period, and models of this procedure indicated that any change in this parameter would not be detected by this instrument. 4 Therefore, this test was discontinued. Retinoscopy. An attempt was made to perform cycloplegic refraction using the Copeland retinoscopy system with the primate under general anesthesia. However, it was difficult to obtain reproducible results using this system, which required the use of loose lenses with the animal in a reclining position. Because of the variability among observers, this test was discontinued and emphasis placed on more objective and reproducible measurements of corneal curvature changes (keratometry). Intraocular pressure. Schiotz tonometry and MacKay Marg tonometry were employed to determine intraocular pressure variations in the pre- and postoperative periods. Three readings were taken with each instrument and the values averaged. Corneal diameter measurements. Corneal diame748
ters were determined in the first six monkeys pre- and post-operatively, measuring from limbus to limbus in the horizontal and vertical meridian. No measureable differences occurred postoperatively, and since theoretical models indicate that any differences that did occur would not be detected by this technique, the study of this parameter was discontinued. 4 SURGICAL TECHNIQUES
Under general anesthesia (sodium pentobarbitol and Ketamine HCl), a wire speculum was inserted, and a 3-mm trephine was used to mark the central optical zone of the primate cornea. Broken razor blade chips or Beaver 76-A blades were used for the radial corneal incisions. Blades were preset using a custom-made Bores animal gauge and a flat-tip blade breaker. The depth of the incision (length of the blade) was set at 90% of the measured central corneal thickness. Radial incisions were made from the optical zone (central 3 mm trephine mark) to the limbus alternating 1800 apart. The eye was fixated at the opposite limbus with a fine tooth forceps to provide counter pressure to the pulling of the blade across the cornea. Incision depth was checked with a Grieshaber microblade, and any incision not of appropriate length or depth was deepened or lengthened with this knife. No attempt was made to dissect down to Descemet's membrane. Any bleeding from limbal vessels was irrigated from the incisions with a balanced salt solution, and the lid speculum was removed after Garamycin drops were instilled. No patch was applied (monkeys pull off any patch almost immediately upon awakening). A Zeiss Opmi 6 operating microscope was used in all cases. Eyes which had perforations during surgery that required either a suture or discontinuation of the surgical procedure without completion of all incisions were eliminated from the study. EXPERIMENTAL DESIGN
Preliminary studies using 16 radial incisions were employed using the stumptail monkey. A second series using owl monkeys was carried out comparing 16 corneal incisions to 8 incisions. The owl monkey has an average keratometry reading of 50.00 ± 1.85 diopters and corneal thickness of 0.46 ± 0.03 mm, while the stumptail has an average keratometry of 55.50 ± 1.49 diopters and a corneal thickness of 0.43 ± 0.03 mm. The owl monkey appeared to have corneal curvature and thickness more approximating that of the human and, therefore, this animal was selected for the comparison of 16 to 8 radial incisions. HISTOPATHOLOGIC STUDIES
Eyes were taken immediately postoperatively, one day, one week, and three months postoperatively fixed in formalin and submitted for routine histopa-
STEEL, et al • RADIAL KERATOTOMY IN PRIMATES
thology. Fixed tissue specimens were embedded in glycol methacrylate and 3 I.t sections made with a glass knife on a Sorvall JB-4 microtome. Sections were stained with hematoxylin and eosin and periodic acidSchiff.
RESULTS CORNEAL CURVATURE CHANGES FOLLOWING RADIAL KERATOMETRY
Terry keratometry readings were not obtainable immediately following the procedure because of distortion to the mires by the incisions. At two weeks, a significant mean decrease (P < 0.005) of 2.75 diopters (D) (range = 1.50-4.00 D) was obtained in the six stumptail monkey eyes, all of which received 16 radial incisions (Table 1, Fig 1). This initial effect in the
STATISTICS
Comparison of pre- and post-operative changes within single monkey groups were made by student t-test for paired comparisons. Comparison between groups of monkeys were made by the student t-test for independent means.
Table 1. Long-term Effects of Radial Keratotomy on Corneal Curvature in the Stumptail Monkey· Animal
Preop
2 wks
4 wks
1. 2. 3. 4. 5. 6.
58.00 55.50 53.75 55.50 53.75 56.00 55.50 1.49
55.75 51.50 49.75 53.75 51.00 54.50 52.75 2.31 <0.005
54.00
Mean SO P-value+
48.25 53.25 51.50 55.50 52.50 2.78 <0.05
6 wks
2 mas
3 mas
4 mas
5 mas
6 mas
54.25 52.25 54.50 51.25 55.50 53.50 1.74 <0.025
51.00 51.25 54.25 53.00 56.25 53.25 2.18
53.75 53.50 51.50 55.00 53.00 55.25 53.75 1.38 <0.025
54.50 54.00 52.00 54.00 52.50 54.75 53.75 1.12 <0.005
54.50 54.00 49.75 54.00 52.75 54.75t 53.00 1.93 <0.025
53.00 54.00 51.00 53.75 52.00
NS
52.75 1.25 <0.025
• Values are recorded as spherical equivalents and have been rounded to the nearest Quarter diopter. t Follow-up is ongoing. P-values obtained by a paired comparison of baseline to postoperative period.
*
1
0 -1 .6K
Fig 1. Long-term effects of radial keratotomy in stumptail monkeys. There was an initial significant 2.75 D flattening effect on the cornea two weeks after surgery (P < 0.005). A slight loss of effect occurred by six weeks postoperatively. However, the corneal curvature change has remained stable for four months with a significant 2.50 D of flattening present six months after surgery (P < 0.025).
-2
(diopters)
-3 -4
I
-5
SEM
-6 1
2
3
4
5
6
MONTHS
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OPHTHALMOLOGY. AUGUST 1981 • VOLUME 88 • NUMBER 8
stumptail appeared to be stable with a significant mean decrease (P < 0.025) of 2.50 D (range = 1.50-5.00 D) present six months after surgery. Only one animal lost greater than 2 D of initial effect (case no. 2, 4.00 D at two weeks to 1.50 D at six months); however, in one animal, corneal curvature continued to flatten over the six-month period (case no. 1, 2.25 D at two weeks to 5.00 D at six months). Some fluctuations in monthly keratometry readings were observed during the longterm analysis with the greatest fluctuation occurring in case no. 3, which varied from 1.75 D to 4.00 D to 2.75 D at four, five, and six months respectively. Determinations of daily variation have not been made. In the ten owl monkey eyes receiving 16 radial incisions, a much greater initial change in corneal curvature was obtained with a significant mean decrease (P < 0.001) of 10.50 D (range = 4.25-16.25 D) occurring two weeks postoperatively (Table 2, Fig 2). Owl monkeys receiving only eight incisions experienced a simTable 2. Change in Corneal Curvature Following Eight and 16 Radial Incisions in Owl Monkeys* Animal 1A 2A 3A 4A 5A 6A 7A 8A 9A 10A Mean
SO
16 Incisions Preop 2 wks 4 wks 6 wks 49.00 46.75 50.25 49.50 49.25 50.25 50.25 54.00 49.50 49.50 49.75 1.78
P-value* *
1B 2B 3B 4B 5B 6B 7B 8B Mean
SO
P-value**
49.75 51.00 49.00 49.50 49.75 51.00 48.25 54.75 50.25 2.00
44.50 43.50 48.00 50.00 48.25 49.25 40.25 48.25 -:j: 44.75 45.75 -:j: 41.75 49.25 45.75 53.50 11 45.25 49.0 11 39.50§ 39.25 46.00 48.50 4.34 4.12 1.66 <.001 <.01 NS Eight Incisions 38.50 39.25 36.50 36.75 33.00
35.75 37.50
-:j:
31.75
-:j: -:j:
40.25 47.25 38.50 5.78 <0.005
2 mos
3 mos
46.00 44.75 50.00 49.00 52.25t 48.25§ 48.75
47.00 46.75 50.00 49.25 52.25t 49.75
47.75 48.50 2.00 1.56 <.025 NS
44.75 48.00 47.75 48.50 50.00 50.25 45.75 48.50 49.00 38.75 49.00 54.00t 45.75 46.75 48.50 47.25 48.00 49.25 47.00 11 53.75 11 46.50 48.25 49.00 4.17 1.09 0.93 <0.025 <0.025 <0.05
48.25 50.00 48.75 56.50t 48.00 49.50 49.00 0.84 <0.025
* Values are recorded as spherical equivalents and have been rounded to the nearest Quarter diopter. t Animals have developed extensive neovascularization with their change in keratotometry outside the 95% confidence interval for all other observation. Animals have, therefore, been considered outlyers and deleted from the study. :j: Values were not obtained because of continued distortion of the Terry Keratometer mires. § Animals have been sacrificed for pathologic analysis. II Follow-up is ongoing. ** P-values obtained by a paired comparison of baseline to postoperative period. 750
ilar effect with an initial significant mean decrease (P < 0.005) of 12.25 D (range = 7.50-17.75 D). In the owl monkey, the effect deteriorated over the following four weeks resulting in a three-month postoperative flattening of only 0.50 D (range 0-2.00 D) in the 16incision group, which was not significant, and a flattening of 1.25 D (range 0.25-1.75 D), which was significant (P < 0.025) in the eight-incision group. Although a slight difference was observed between the eight- vs 16-incision groups at three months, this difference was not significant. Furthermore, the overall effects of these two procedures were not significantly different. Extensive neovascularization developed in case nos. 5A and 4B. Surgery and follow-up in both cases were unremarkable, and there is no explanation for the postoperative complication. In both cases, the corneal curvature has continued to steepen postoperatively with values at three months of +3.00 D and + 7.00 D, respectively. These changes are outside the 95% confidence interval for the changes observed in all other animals. Therefore, these responses have been considered as outlying and deleted from the study. It is interesting to note that these two cases also exhibited the greatest initial change in corneal curvature with a flattening of 16.25 D and 17.25 D at two weeks. A marked significant difference (P < 0.001) was noted in the effect on corneal curvature at two weeks between the owl monkeys receiving 16 incisions and the stump tail monkeys receiving 16 incisions, with the owl monkeys exhibiting the greater effect (Table 3). However, this difference was not observed long-term and tended to reverse by three months, at which time almost all of the effect had been lost in the owl monkey. PACHOMETRY CHANGES FOLLOWING RADIAL KERATOMETRY
Sixteen radial incisions had no effect on corneal thickness in stumptail monkey eyes; however, a significant mean increase of 0.13 ± 0.06 mm at two weeks and 0.04 ± 0.04 mm at four weeks was noted in the corneal thickness of owl monkey eyes receiving 16 incisions (P < 0.001 and P < 0.05, respectively) (Table 4). Although corneal thickness returned to normal by six weeks and remained stable in the owl monkey, the initial effect was significantly different than that which occurred in stumptail monkeys (P < 0.001). Owl monkeys receiving only eight incisions experienced a similar significant mean increase of 0.09 ± 0.06 mm (P < 0.005) at two weeks but returned to normal by four weeks and remained stable (Fig 3). Although eight incisions appeared to have less of an effect on corneal thickness than 16 incisions, no significant difference was detected. CHANGES IN CENTRAL ENDOTHELIAL CELL DENSITY FOLLOWING RADIAL KERATOTOMY
All observations were made in the 3 mm optical zone, and no attempt was made to determine endothelial cell densities in the peripheral cornea. In owl mon-
STEEL, et al • RADIAL KERATOTOMY IN PRIMATES
2
o
-----------
-2 -4
-6 (dlopters)
-8
-10
•
• 16 INCISIONS
c-----:)
-12
I
8 INCISIONS
SEM
Fig 2. Change in corneal curvature following eight vs 16 incisions in owl monkeys. An initial flattening of 10.50 D in eyes receiving 16 incisions and 12.25 Din eyes receiving eight incisions occurred in this species. The effect rapidly deteriorated over the following four weeks. There was no statistically significant difference between the effect on corneal flattening by eight incisions as compared to 16 incisions.
-14
4
2
12
10
8
6 WEEKS
keys, four out of ten eyes receiving 16 incisions and three out of eight eyes receiving eight incisions have demonstrated a 10%-20% decrease in their central endothelial cell densities three months postoperative (Table 5). Four of the seven cases did not exhibit significant changes until two to three months after Table 3. Comparison of Change in Corneal Curvature Between Owl Monkeys and Stumptail Monkeys Following 16 Radial Incisions Monkey Owl # Mean SO Stumptail # Mean SO P-value
~K'
surgery (case nos. 6A, IB, 2B, and 4B). Therefore, further analysis is necessary to determine any significant long-term changes. No change was observed in the stumptail monkeys. (This species apparently has a regenerative endothelium, and long-term cell loss would not be expected. 5) Table 4. Comparison of Change in Pachometry Between Owl Monkeys and Stumptail Monkeys following 16 Radial Incisions ~
2 wks
4 wks
6 wks
2 mos
3 mos
8 -10.50 3.82 6 -2.75 1.09 <0.001
9 -4.00 3.21 5 -3.00 1.91 NS
5 -1.25 1.66 5 -1.25 .74 NS
6 -1.50 1.01 5 -1.75 1.83 NS
5 -0.50 0.80 6 -1.75 1.42 NS
* Values are reported as the average change in spherical equivalents rounded to the nearest quarter diopter comparing baseline to the follow-up period. t P-values obtained by a comparison of independent means.
Monkey Owl # Mean SO Stumptail # Mean SO P-value:j:
2 wks 10 0.13t 0.06 6 0.01 0.02 <0.001
Corneal thickness' 6 wks
2 mos
3 mos
6 8 0.03 0.04t 0.04 0.04 3 5 -0.01 0.01 0.04 0.02 NS NS
7 0.01 0.02 3 -0.01 0.03 NS
6 0.01 0.02 5 -0.03 0.07 NS
4 wks
• Values are averages of individual changes from baseline to the followup period. t Values significantly elevated above baseline levels. :\: P-values obtained by a comparison of independent means.
751
OPHTHALMOLOGY. AUGUST 1981 • VOLUME 88 • NUMBER 8
.60-
PACHOMETRY (mm)
.50
...- - -•• 16 INCISIONS
. 40-
r
---
Fig 3. Changes in corneal thickness following radial keratotomy in owl monkeys two weeks a fter surgery. There was a sig. nificant in crease in the corneal thickness for both groups receiving eight and 16 incisions (P < 0.005 and P < 0.001 respectively). The corneal thickness has returned to normal and remained stable .
8 INCISIONS SEM
WEEKS
Table 5. Change in Corneal Endothelial Cell Densities Following Eight and 16 Incisions in Owl Monkeys· Animal
Preop
lA 2A 3A 4A 5A 6A 7A SA 9A lOA
2111 2050 2350 1833 2483 2450 2133 2217 2633 2217
lB 28 3B 4B 5B 6B 7B 88
2617 2417 1900 2267 2033 2300 2483 2983
2 wks
16 Incisions 4 wks 6 wks 1900t 1668t 2230 1850 2083 2367 1933 2017 2733
2250 2150 1850 1833 2183 1867t 2283 2333 2217 2100 2200§ 2275 2617§ 2683 2275:f: Eight Incisions 2450 2200 1900 2317 2050 2200 2417 3000
2400 2333 1967 1950 2067 2033 2283 2867
2517 2300 1817 2100 1983 2250 2383§ 2933§
• Values reported as numbers of cells per mm2.
t Represents a 10%-20% cell decrease.
:j: Animal sacrificed for pathologic analysis. § Follow-up is being continued .
752
2 mos
3 mos
1583t 1768t 2180 1967 1983t 2217t:t; 2067
1700t 1750t 2133 1817 1867t 1983
CHANGES IN TONOMETRY
No significant changes in intraocular pressure were noted in any of the groups studied. There was a slight tendency toward an increase in pressure immediately postoperative and at two weeks as followed by Schoitz tonometry in owl monkeys. This effect resolved by one month with stable three-month readings averaging slightly lower than preoperative values (Fig 4). AIthough not significant, these values may be artificially low due to changes in sclera] rigidity caused by this procedure. Measurements by MacKay Marg tonometry did not reflect a similar decrease in pressure. COMPLICATIONS
2383 2133t 1883 1850t 1967 2117
2250t 2033t 1867 1883t 1967 2150
Of 28 operative procedures, six (20%) ended with a clinically evident perforation. Four (14%) resulted in termination of the procedure before completion of the surgery . One perforation that was not repaired at surgery resulted in an iris prolapse. Varying degrees of corneal vascularization have been noted particuiarly in cases with peripheral perforations. Two cases which did not have any clinical signs of perforation have developed 3600 of neovascularization extending twothirds of the way to the 3 mm optical zone . Cases that required sutures to close the perforation site developed variable degrees of irregular astigmatism.
STEEL, et al • RADIAL KERATOTOMY IN PRIMATES
20 Fig 4. Changes in intraocular pressure following radial keratotomy in owl monkeys. Initially, there was a slight but not significant elevation in pressure following eight and 16 radial incisions, as measured by Schiotz tonometry. Over the course of the follow-up, the pressure has remained within normal limits averaging slightly lower than preoperative values. These values may be artificially low due to change in scleral rigidity.
16TONOMETRY
(mmHg)
12-
T
,T
.L- _ _
8-
----------.1
T....... .........1 •
• ----
r
4-
2
4
8
6
10
16 INCISIONS 8 INCISIONS SEM
12
WEEKS
HISTOPATHOLOGY
By one day postoperatively, ingrowth of corneal epithelium into the stromal wounds was evident along with a slight infiltration of polymorphonuclear leukocytes. The epithelial plug was replaced by one week with a dense cellular infiltrate offibroblasts. Any presence of extracellular matrix deposition was not remarkable at this stage of healing. After three months, healing appeared complete with reapproximation of the wound margins, disappearance of all but afew of the associated fibroblasts, and minimal deposition of new collagenous matrix (Fig 5). A slight thickening of epithelium over the scar was also seen. No histologic damage was noted to the endothelium or angle structure.
DISCUSSION The current study in primates demonstrates the variability between two primate species in the initial effect and in the stability of long-term results. Initial corneal curvature changes were greater in owl monkeys than in stumptails using the same standard procedure of 16 corneal incisions. On the other hand, the long-term result was much more stable in the stumptail. In the owl monkey, there was a gradual return toward the original preoperative shape of the cornea with resultant loss of most of the initial corneal curvature change over a period of four to six weeks. After several months, an average of 2 or 3 diopters of corneal curvature flattening was present in stumptails compared to 1 diopter of flattening in owl monkeys. It is interesting to speculate as to the cause of this regression of corneal curvature. It is possible that
,I' ,f'
"'"
, ,
Fig S. Corneal scar in the owl monkey three months after radial keratotomy. Healing appeared complete with reapproximation of the wound margins (arrow) and minimal deposition of new collagenous matrix (hematoxylin and eosin, original magnification x 120).
753
OPHTHALMOLOGY. AUGUST 1981 • VOLUME 88 • NUMBER 8
rapid wound healing results in a tendency for the cornea to return to its original curvature. Some clinicians have, therefore, suggested the use of patching and corticosteroids to stabilize the acute corneal curvature effects by holding the incision sites in a more open position and allowing a delayed healing by secondary intention. However, the degree of visible scarring does not appear to correlate directly with the flattening effect. (One stumptail with 4 diopters of effect at six months had an almost invisible scar.) Nevertheless, it is postulated that the flattening of the central cornea is due to opening of surface of incisions and healing with some residual gap between original edges of the incision with subsequent deposition of new collagen. The larger the deposition of new collagen, the less wound retraction and. wound molding, and, therefore, the larger residual effect. There is no laboratory evidence to support these theories at the present time. A second study reported here compares eight incisions to 16 incisions using the same incision length and optical zone site. We could detect no difference between the change in corneal curvature in the two groups three months postoperative. We are continuing to follow these animals in order to detect any longterm differences. Histopathologic studies demonstrated typical avascular corneal wound healing. There is an initial sliding of the epithelium to fill the surface defect. Stromal areas develop increased fibroblast activity in the wound site which gradually pushes the epithelial plug to the surface. Gradual reorganization and molding of the wound with new collagen begins to diminish the visibility of the scar. Histopathologic examinations also demonstrated the variation in the depth of inci-
754
sions despite attempts by the surgeon to make incisions of equal depth. This variability in the depth of incisions is probably a factor in the unpredictability of this procedure both in primates and humans to date. Complications occurred during these animal studies and included surgical perforation, followed by irregular astigmatism, corneal neovascularization, and a 10- 20% decrease in central endothelial cell densities.
ACKNOWLEDGMENT The authors thank Lawrence Rife, Kate Borkowski, Bob Zink, and Ann Guild for their expert technical assistance necessary for the completion of this study and manuscript.
REFERENCES 1. Fyodorov SN. Durnev VV. Operation of dosage dissection of corneal circular ligament in cases of myopia of mild degree. Ann Ophthalmol 1979; 11: 1885-90. 2. Joseph NH, Popp JC. Superficial radial keratotomy in rabbits. In: Schachar RA, Levy NS, Schachar L eds. Keratorefraction. Proceedings of the Keratorefractive Society Meeting. Denison, Texas: LAL Publishing, 1980: 135-40. 3. Azen SP, Burg KA, Smith RE, Maguen E. A study in the measurement of corneal endothelial cell density using the specular microscope. Acta Ophthalmol 1980; 58:418-23. 4. Schachar RA, Black TO, Huang T. A physicist view of radial keratotomy practical with surgical implications. In: Schachar RA, Levy NS, Schachar L eds. Keratorefraction. Proceedings of the Keratorefractive Society Meeting. Denison, Texas; LAL Publishing, 1980; 195-220. 5. Van Horn DL, Hyndiuk RA. Endothelial wound repair in primate cornea. Exp Eye Res 1975; 21:113-24.