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Quantitated Trauma Following Radial Keratotomy in Rabbits
Quantitated Trauma Following Radial Keratotomy in Rabbits
BRUCE C. LARSON, MD, FREDERIC B. KREMER, MD, ANDREW W. ELLER, MD, VITALIANO B. BERNARDINO, JR., MD
Abstract: Radial keratotomy was performed in 33 rabbits using an eightincision technique. At various postoperative intervals up to 90 days, these eyes were enucleated and subjected to increasing quantitated trauma until ocular rupture occurred. Control animals (13 eyes) were subjected to similar trauma. The eyes that had surgery required approximately 50% of the control energy to rupture over the 90-day period (P < 0.001). Corneal microperforations at surgery greatly increased the trauma risk (P = 0.02). Consistent rupture patterns resulted, both grossly and microscopically. [Key words: anterior radial keratotomy, radial keratoplasty, radial keratotomy, refractive surgery, trauma-related keratotomy.] Ophthalmology 90:660-667, 1983
Anterior radial keratotomy was developed by Fyodorov l of the Soviet Union to modify corneal curvature and thereby reduce refractive error in myopes. The procedure has subsequently been substantiated as effective by various investigators in the United States. 2-4 This study evaluates the effect of radial keratotomy on subsequent resistence to blunt ocular trauma over a finite period (90 days) in rabbits. The energy levels required for ocular rupture following various postoperative healing intervals were determined. The resultant injuries were also characterized.
MATERIALS AND METHODS Thirty-nine adult New Zealand albino rabbits, weighing between 8 and 10 pounds, were included in the study. They were divided into control, 1-, 10-, 30-, and 90-day postoperative groups.
The experimental animals were sedated with intramuscular ketamine and acepromazine, and topical proparacaine was applied. A wire lid speculum was inserted. A central optical zone 3 mm in diameter was marked on the corneal epithelium with a Hoffer marking trephine. Central corneal thickness was measured at four points along the border of the central optical zone using an Accutome Corneometer ultrasonic pachymeter. The instrument was modified to increase the range of measurement for the thinner rabbit cornea_ A Feather blade in a Swiss blade holder was positioned with a length of 0.02 mm less than the minimum corneal thickness measurement. Eight equidistant, partial-thickness, radial incisions were then placed such that each started at the central optical zone and extended to approximately 1 mm from the limbus (Fig 1). All complications and observations were recorded. No topical medications were used after surgery. The keratotomy incisional depth and change in corneal curviture were not evaluated. QUANTITATED TRAUMA
From Wills Eye Hospital, Thomas Jefferson University, and University of Pennsylvania, Philadelphia, Pennsylvania. Presented at the Eighty-seventh Annual Meeting of the American Academy of Ophthalmology, San Francisco. California, October 30-November 5, 1982. Supported in part by the Wills Eye Hospital Research Department. Reprint requests to Frederic B. Kremer, MD, 19th and Lombard Streets, Suite 607, Pepper Pavilion, Philadelphia, PA 19146.
660
After postoperative intervals of 1, 10, 30, and 90 days, the animals were killed and their eyes were enucleated. The eyes were then placed a trauma-delivery device (Fig 2). This device consisted of four components: (1) a 12ounce (13f4-inch diameter) steel ball bearing; (2) a ballbearing track measuring 12 feet, constructed of I-inch aluminum angle iron oriented at 45°; (3) an energy transmitter to deliver the kinetic energy from the ac-
0161-6420/83/0600/0660/$1.20 © American Academy of Ophthalmology
LARSON,
et al • QUANTITATED TRAUMA
celerated bearing to the center of the recipient cornea (constructed of a 3f4-inch cylindrical wooden striker with a modified 1/4-inch blunt cylindrical wooden tip with an overall weight of 0.5 ounces, and housed in a 3f4-inch copper barrel in a freely movable fashion); (4) a wooden trauma-receiving block with a spherical Sfs-inch diameter depression to support the globe. This was positioned against a wall that served as a rigid backstop. The trauma-delivery protocol for all eyes (experimental and control) consisted of the same series of progressively increased trauma. In trial 1, the ball bearing was released from a distance of 21f4 inches; in trial 2, from a distance of 41/2 inches; in trial 3, from a distance of 9 inches. Each successive trauma delivered twice the energy of the preceding trial. The eyes were examined after each trial. Trauma delivery to each eye was terminated after ocular rupture; the eyes were then placed in 10% formalin and submitted for pathologic evaluation. TRAUMA ENERGY CALCULATIONS
Energy = Force X distance = (Mass) X (Gravity) (distance along track) X Cos 45°. Angular inertia and friction were small and disregarded. The energy absorbed by the wooden striker device was also disregarded because the weight was less than 5% of the bearing weight. X
HISTOLOGY
The eyes were examined grossly and were sectioned to demonstrate incisions and perforations. The sections were stained with hematoxylin-eosin; these were reviewed histologically to observe wound healing and patterns of perforations.
RESULTS
Fig 1. Typical appearance of rabbit eye following radial keratotomy procedure.
frequent pattern (26%) was a radial corneoscleral laceration with the corneal segment representing a break along a corneal incision (Table 2). In several cases, the scleral ruptures extended posteriorly to the optic nerve. The third most frequent pattern (20%) was the "stellate" rupture; this was similar to the cut-to-cut, except that three or more (up to five) of the corneal incisions broke apart and connected to form a single complex corneal laceration (Table 2). The fourth most frequent pattern (17%) was the "incision-opening" rupture in which one incision ruptured and did not extend (Table 2). Only one experimental eye ruptured with the pattern of an optic-nerve avulsion. One experimental eye ruptured in an incision-opening variant pattern with an extension across two adjacent incisions (see Table 2-"other").
The energy required for rupture and the pattern of rupture of all eyes are displayed in Table 1. As indicated, ten eyes were used to evaluate the histology of uninterrupted wound healing. Other eyes were discarded for various reasons as indicated. Microperforations occurred in seven eyes at the time of surgery which were evaluated separately below. RUPTURE PATTERN
The various patterns of rupture for the experimental and control groups are graphically demonstrated and tabulated in Table 2. Ninety-eight percent of the eyes that had surgery ruptured in a corneal or corneoscleral laceration. These ruptures incorporated one or more breaks along the corneal incisions. The most frequent rupture pattern (33%) was a "cut-to-cut" rupture in which two of the corneal incisions were involved in a single corneal laceration (Table 2). The second most
Fig 2. Trauma delivery device transmits kinetic energy from an accelerated ball bearing directly to the central corneal surface of the enucleated rabbit eyes.
661
OPHTHALMOLOGY • JUNE 1983 • VOLUME 90 • NUMBER 6
Table 1. (continued)
Table 1. Summary of Quantitated Trauma Results
Animal Control
61
62 63 64 65 66 67
Eye R L R L R L R L R L R L R L
Energy to Rupture (trials) Pathology
5 7 8 5 5
Pathology
5 5 5 6 5 6 6
Mean (R + L) (trials)
5.0 7.5 5.0 5.0 5.0 5.5 6.0
Rupture* Pattern
CS CS CS ON CS CS CS OT CS ON ON ON
Day 1
51 52 53 54 55 56 57
Day 10 -31-
32 33 34 35 36 37 38 39
R L R L R L R L R L R L R L R L R L R L R L R L R L R L R L R L
5
Pathology
6 4
Pathology
5 3 4 4 4 2 5 4 5
Endophthalmitis
4 2 1 4
5.0 5.0 5.0 3.5 4.0 3.5 4.5
4.0
CC ST ST ST 10 ST CC CS 10 CC CS ST
1 (Perf) 5 3 4 4
4.0
CS 10 10 CS 10 CC CS CC CS
3
3.0
CS
3 3 5 4 5
3.0
10 CC ST CS CC
Pathology Pathology
1.5 4.0 4.0
4.0 4.5
Day 30
-1011 13
662
R L R L R L
4 3 6 5 5 5
3.5 5.5 5.0
CC 10 CC ST OT CS
Animal
Eye
14
R L R L R L R L
15 16 17
Energy to Rupture (trials)
Mean (R + L) (trials)
3 (Perf) 6 4
6.0
Rupture* Pattern 10 CC ST
4.0
Pathology Pathology 3 (Perf)
5 3
4.0
CS CC ON
4.0
ST 10 10 CC
Day 90
1 2 3 4 5 6 7 8 9
4 (Perf) 4 (Perf) 4 4
R L R L R L R L R L R L R L R L R L
Pathology
4 5
4.0
ST CC
5.0
Old scar Infection 3 (Perf)
5 3
4.0
Pathology
4.0
4 7 5
6.0
4 (Perf) 4
4.0
10 CS CS (CC CC (CC CS 10
+ CS) + CS)
Rupture patterns: * CC = cut-to-cut, CS = corneoscleral, ST = stellate, 10 = incisionopening, ON = optiC nerve avulsion, OT = other, CC + CS = cut-tocut with corneoscleral extension (statistically counted as 1f2 CC and 1f2 CS). See text for descriptions.
In the group of control eyes, 58% ruptured in a radiating corneoscleral pattern. Most of the remaining eyes ruptured with optic-nerve avulsions (33%), which were Table 2. Distribution of Specific Injuries Control Rupture Pattern "Cut-to-cut" Corneo-scleral Incision opening Stellate OptiC nerve avulsion Other Total
Experimental (All Groups)
No.
%
No.
%
~
0
0
15
33
,
-
7
58
12
26
-
0
0
8
17
0 4
0 33
9
20 2
8
1
2
99%
46
100%
Example
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LARSON, et al •
QUANTITATED TRAUMA
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0
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..J
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~
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6
~
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0
2
0 .....
Experimental (All Groups)
Control
"
Injury
Incidence/ Total
Lens/vitreous avulsion Iris-root dialysis Iris prolapse
7/12 5/12 1/12
-- - - - ---~ ~
4
m
:l
Table 3. Distribution of Miscellaneous Injuries
L...--t-...., r--+-,+-b---31I-o----------1~o <5
%
Incidence/ Total
%
15/46 17/46 9/46
33 37 20
58 42
8
Note. Essentially 100% develop corneal abrasions; essentially 100% develop gaping of keratotomy incisions.
~
z a
u
DAYS POST OPERATIVE
Fig 3. Graph of energy to rupture vs. time. Each dot represents the mean of right and left eyes when both eyes were available.
rare in the experimental group (2%). One control eye ruptured with an isolated scleral laceration (8%), which did not occur in the experimental group. Other miscellaneous ocular injuries were observed frequently in both experimental and control groups and are listed in Table 3. Essentially all operated eyes developed gaping of corneal incisions, which increased after successive trials. The gaping progressed in many eyes to grossly visible lamellar corneal stromal dissection extending away from the base of the corneal incisions. In some cases, this dissection was manifested by the appearance of large sheets of corneal tissue folded back on itself. ENERGY REQUIRED FOR RUPTURE
All analyses and graphs presented here use the average of right and left eyes for a given animal when both eyes were available here. The energy required for ocular rupture in the various experimental groups over the 90-day study is graphically illustrated (Fig 3). The logarithmic scale along the "Y" axis corresponds to the number of trials of doubling energy which were required for rupture. The control group required a mean of 5.57 trials (3.2 joules) to rupture. When all experimental groups were combined, they required a mean of 4.46 trials to ruptur~, 46% of the control energy (P < 0.001). Each of the four groups was also compared individually with the control group, and the differences are shown in Table 4 and Figure 3. The day 1 and day 10 groups were found to require significantly less energy to rupture as compared to the control group (Dunnet's method of analysis). The day 30 and day 90 groups were found to require a reduced energy compared to the controls. Because of the small number of animals used in this study, a real difference was strongly suggested but not statistically significant. The wound strength for each of the postoperative intervals was similar.
CORNEAL MICROPERFORATIONS
Six eyes of five rabbits had single corneal microperforations during surgery. A macroperforation occurred in a sixth rabbit. These eyes were excluded from all previous analyses and are described separately. The six animals in this group required from one to four trials for rupture to occur, with a mean value of 3.0 trials. This represents less than 50% of the energy required for rupture of the operated eyes without perforation (mean of 4.13 trials, range of 1.5-6.0 trials). This difference was significant (P = 0.02, t-test). Eyes traumatized following radial keratotomy were studied histologically. Three patterns of corneal injury prevailed in all four of the operated groups. "Wound gape," in which the wound margins separated for the entire depth of the incision (Fig 4), was the earliest pattern identified prior to perforation. In the second and more progressive pattern, "lamellar dissection," a wound gape was seen in association with a horizontal dissection (or splitting in lamellar fashion) of corneal stromal fibers away from the base of the incision. The inner fibers and Descemet's membrane remained intact (Fig 5). The third pattern, corneal perforation, was seen as an exten~ sion of the previously described patterns. In each case of perforation, an area of wound gape and lamellar dissection was identified. In addition, an area of perforation through the remaining inner corneal fibers was also demonstrated (Fig 6). The perforation has been noted to occur at any point along the area of lamellar dissection, not necessarily in direct line with the radial keratotomy incision. Corneal perforations of traumatized normal Table 4. Energy to Rupture vs Time Group
Energy to Rupture (joules)
% of Control
P
Control Day 1 Day 10 Day 30 Day 90
3.2 1.4 0.8 1.7 1.7
100 43 25 54 52
<0.05 0.01 0.1 >0.05
663
OPHTHALMOLOGY •
JUNE 1983 •
VOLUME 90 •
NUMBER 6
-'
'.
.
-.
--
---
-.- . Fig 4. Wound gape: separation of wound edges following lesser trauma.
Fig 5. Lamellar stromal dissection: with additional trauma, wound gape typically develops a lamellar split of stromal fibers away from the base of the wound.
664
--
LARSON, et al •
QUANTITATED TRAUMA
Fig 6. Corneal perforation. Only one of the wound edges is shown. After wound gape progressed to lamellar dissection, additional trauma perforated Descemet's membrane well away from the original wound gape.
eyes without radial keratotomy showed jagged or frayed edges of lamellar fibers throughout the entire depth of the perforation (Fig 7). There was no significant lamellar dissection of corneal stroma in control eyes.
DISCUSSION This study evaluated the relative risk of blunt trauma to rabbit eyes following radial keratotomy, over a period of 90 days. Significant differences were found between eyes with radial keratotomy and controls with regard to energy requirement for rupture and patterns of injury. Rabbit eyes required 54% less energy for rupture following radial keratotomy (P < 0.001). The energy required for rupture; did not vary significantly over the 90day study (Fig 3). When microperforations occurred during the procedure, this further reduced the subsequent energy required to rupture by an additional 50% (P = 0.02). This suggests that corneal microperforation may represent a significant operative complication and should be avoided.
Precise measurement and mapping of corneal thickness before and during surgery is essential to help prevent such perfon~tions. Protective eyewear in the postoperative period may be of benefit in some patients. The patterns of rupture varied significantly between control eyes and eyes that had undergone radial keratotomy. Ninety-eight percent of the operated eyes ruptured along one or more corneal incisions, with or without extension along the sclera. Optic nerve avulsions were common in the control group (33%) and rare in the keratotomy group (2%). This observation raises the question as to whether the corneal incisions may act as protective release valve against more serious injury. Operated eyes were studied histologically following various degrees of trauma. The following progressive corneal injury patterns were found: wound gape, wound gape plus lamellar corneal stromal dissection, and eventual perforation in conjunction with the above patterns. Control eyes did not demonstrate this progression. A direct correlation of this paper with the human risk of trauma is not possible for a variety of reasons. These include rabbit corneal differences, the use of enucleated eyes, and the effect of repeated trauma to individual eyes. 665
OPHTHALMOLOGY •
JUNE 1983 •
VOLUME 90 •
NUMBER 6
Fig 7. Corneal perforation in, a control eye shows frayed edges of the wound throughout the entire depth of the perforation. No significant lamellar stromal dissection is seen.
The rabbit cornea varies anatomically with the human cornea. 5 The rabbit cornea has a larger diameter and is thinner in depth. Bowman's membrane in the rabbit is thinner and is difficult to identify without electron microscopy. The rabbit endothelium is also capable of regeneration. The rabbit, therefore, provides a poor model for study of endothelium and Descemet's membrane, which was not attempted. Trauma was applied to enucleated eyes to isolate specifically the ocular resistance to rupture. The protective effects of the orbit, including compressible fat and the potential for blowout orbital fractures, were thereby eliminated. This would be likely to modify the energy required for rupture and possibly the resultant ocular injuries. Traumatic energy was delivered in repeated, doubling doses to individual eyes until rupture occurred. This conserved the number of animals required for study but may have modified both the energy required for rupture and the resultant injuries. The ocular injuries created in this study differ from previously reported human series of ocular rupture. Cherry reported on 34 cases of blunt trauma resulting in rupture of the globe.6 Isolated limbal and scleral lac-
666
erations accounted for 89% of his cases. None were present in our radial keratotomy group, and only 8% occurred in our control group. Isolated corneal lacerations did not occur in his patients, whereas 72% of our operated rabbit~ and none of our controls ruptured as isolated corneal patterns. Cherry described corneoscleral lacerations in 11 % of patients, as compared with our operated group (26%) and controls (58%). Optic nerve avulsions did not occur in his series. These results suggest a shift away from limbal or scleral ruptures toward corneal lacerations. This may be due to the presence of the incompletely healed corneal incisions or due to the method of trauma used in this study delivering the greatest energy to the recipient cornea in a manner different from most commonly encountered human blunt trauma. Further studies are warranted to evaluate better the trauma risk following radial keratotomy. Primate eyes would better approximate the human globe. Future similar studies should use one eye for each animal as a control. It became evident that right and left eyes of a given animal required similar degrees of trauma to rupture. A more prolonged study period is needed to more accurately reflect the long-term resistance to trauma.
LARSON, et al •
ACKNOWLEDGMENT Statistical analysis was provided by Hyman Menduke, PhD, Thomas Jefferson Medical College, Philadelphia, Pennsylvania.
REFERENCES 1. Fyodorov SN, Durnev W. Operation of dosaged dissection of corneal circular ligament in cases of myopia of mild degree. Ann Ophthalmol 1979; 11 :1885-90.
QUANTITATED TRAUMA
2. Schacher RA, Levy NS, Schachar L, eds. Refractive Modulation of the Cornea. Proceedings of the Kerato Infractive Society Meeting on Radial Keratotomy and Keratorefraction. Denison, TX: LAL Publishing Co., 1981. 3. Bores LD, Myers W, Cowden J. Radial keratotomy: an analysis of the American experience. Ann OphthalmoI1981; 13:941-8. 4. Hoffer KJ, Darin JJ, Pettit TH. UCLA clinical trial of radial keratotomy; preliminary report. Ophthalmology 1981; 88:729-36. 5. Prince JH. The Rabbit in Eye Research. Springfield, IL: Charles C Thomas, 1964; chapter 6. 6. Cherry PM. Rupture of the globe. Arch Ophthalmol 1972; 88:498-
507.
667
BRUCE C. LARSON, MD, FREDERIC B. KREMER, MD, ANDREW W. ELLER, MD, VITALIANO B. BERNARDINO, JR., MD
Abstract: Radial keratotomy was performed in 33 rabbits using an eightincision technique. At various postoperative intervals up to 90 days, these eyes were enucleated and subjected to increasing quantitated trauma until ocular rupture occurred. Control animals (13 eyes) were subjected to similar trauma. The eyes that had surgery required approximately 50% of the control energy to rupture over the 90-day period (P < 0.001). Corneal microperforations at surgery greatly increased the trauma risk (P = 0.02). Consistent rupture patterns resulted, both grossly and microscopically. [Key words: anterior radial keratotomy, radial keratoplasty, radial keratotomy, refractive surgery, trauma-related keratotomy.] Ophthalmology 90:660-667, 1983
Anterior radial keratotomy was developed by Fyodorov l of the Soviet Union to modify corneal curvature and thereby reduce refractive error in myopes. The procedure has subsequently been substantiated as effective by various investigators in the United States. 2-4 This study evaluates the effect of radial keratotomy on subsequent resistence to blunt ocular trauma over a finite period (90 days) in rabbits. The energy levels required for ocular rupture following various postoperative healing intervals were determined. The resultant injuries were also characterized.
MATERIALS AND METHODS Thirty-nine adult New Zealand albino rabbits, weighing between 8 and 10 pounds, were included in the study. They were divided into control, 1-, 10-, 30-, and 90-day postoperative groups.
The experimental animals were sedated with intramuscular ketamine and acepromazine, and topical proparacaine was applied. A wire lid speculum was inserted. A central optical zone 3 mm in diameter was marked on the corneal epithelium with a Hoffer marking trephine. Central corneal thickness was measured at four points along the border of the central optical zone using an Accutome Corneometer ultrasonic pachymeter. The instrument was modified to increase the range of measurement for the thinner rabbit cornea_ A Feather blade in a Swiss blade holder was positioned with a length of 0.02 mm less than the minimum corneal thickness measurement. Eight equidistant, partial-thickness, radial incisions were then placed such that each started at the central optical zone and extended to approximately 1 mm from the limbus (Fig 1). All complications and observations were recorded. No topical medications were used after surgery. The keratotomy incisional depth and change in corneal curviture were not evaluated. QUANTITATED TRAUMA
From Wills Eye Hospital, Thomas Jefferson University, and University of Pennsylvania, Philadelphia, Pennsylvania. Presented at the Eighty-seventh Annual Meeting of the American Academy of Ophthalmology, San Francisco. California, October 30-November 5, 1982. Supported in part by the Wills Eye Hospital Research Department. Reprint requests to Frederic B. Kremer, MD, 19th and Lombard Streets, Suite 607, Pepper Pavilion, Philadelphia, PA 19146.
660
After postoperative intervals of 1, 10, 30, and 90 days, the animals were killed and their eyes were enucleated. The eyes were then placed a trauma-delivery device (Fig 2). This device consisted of four components: (1) a 12ounce (13f4-inch diameter) steel ball bearing; (2) a ballbearing track measuring 12 feet, constructed of I-inch aluminum angle iron oriented at 45°; (3) an energy transmitter to deliver the kinetic energy from the ac-
0161-6420/83/0600/0660/$1.20 © American Academy of Ophthalmology
LARSON,
et al • QUANTITATED TRAUMA
celerated bearing to the center of the recipient cornea (constructed of a 3f4-inch cylindrical wooden striker with a modified 1/4-inch blunt cylindrical wooden tip with an overall weight of 0.5 ounces, and housed in a 3f4-inch copper barrel in a freely movable fashion); (4) a wooden trauma-receiving block with a spherical Sfs-inch diameter depression to support the globe. This was positioned against a wall that served as a rigid backstop. The trauma-delivery protocol for all eyes (experimental and control) consisted of the same series of progressively increased trauma. In trial 1, the ball bearing was released from a distance of 21f4 inches; in trial 2, from a distance of 41/2 inches; in trial 3, from a distance of 9 inches. Each successive trauma delivered twice the energy of the preceding trial. The eyes were examined after each trial. Trauma delivery to each eye was terminated after ocular rupture; the eyes were then placed in 10% formalin and submitted for pathologic evaluation. TRAUMA ENERGY CALCULATIONS
Energy = Force X distance = (Mass) X (Gravity) (distance along track) X Cos 45°. Angular inertia and friction were small and disregarded. The energy absorbed by the wooden striker device was also disregarded because the weight was less than 5% of the bearing weight. X
HISTOLOGY
The eyes were examined grossly and were sectioned to demonstrate incisions and perforations. The sections were stained with hematoxylin-eosin; these were reviewed histologically to observe wound healing and patterns of perforations.
RESULTS
Fig 1. Typical appearance of rabbit eye following radial keratotomy procedure.
frequent pattern (26%) was a radial corneoscleral laceration with the corneal segment representing a break along a corneal incision (Table 2). In several cases, the scleral ruptures extended posteriorly to the optic nerve. The third most frequent pattern (20%) was the "stellate" rupture; this was similar to the cut-to-cut, except that three or more (up to five) of the corneal incisions broke apart and connected to form a single complex corneal laceration (Table 2). The fourth most frequent pattern (17%) was the "incision-opening" rupture in which one incision ruptured and did not extend (Table 2). Only one experimental eye ruptured with the pattern of an optic-nerve avulsion. One experimental eye ruptured in an incision-opening variant pattern with an extension across two adjacent incisions (see Table 2-"other").
The energy required for rupture and the pattern of rupture of all eyes are displayed in Table 1. As indicated, ten eyes were used to evaluate the histology of uninterrupted wound healing. Other eyes were discarded for various reasons as indicated. Microperforations occurred in seven eyes at the time of surgery which were evaluated separately below. RUPTURE PATTERN
The various patterns of rupture for the experimental and control groups are graphically demonstrated and tabulated in Table 2. Ninety-eight percent of the eyes that had surgery ruptured in a corneal or corneoscleral laceration. These ruptures incorporated one or more breaks along the corneal incisions. The most frequent rupture pattern (33%) was a "cut-to-cut" rupture in which two of the corneal incisions were involved in a single corneal laceration (Table 2). The second most
Fig 2. Trauma delivery device transmits kinetic energy from an accelerated ball bearing directly to the central corneal surface of the enucleated rabbit eyes.
661
OPHTHALMOLOGY • JUNE 1983 • VOLUME 90 • NUMBER 6
Table 1. (continued)
Table 1. Summary of Quantitated Trauma Results
Animal Control
61
62 63 64 65 66 67
Eye R L R L R L R L R L R L R L
Energy to Rupture (trials) Pathology
5 7 8 5 5
Pathology
5 5 5 6 5 6 6
Mean (R + L) (trials)
5.0 7.5 5.0 5.0 5.0 5.5 6.0
Rupture* Pattern
CS CS CS ON CS CS CS OT CS ON ON ON
Day 1
51 52 53 54 55 56 57
Day 10 -31-
32 33 34 35 36 37 38 39
R L R L R L R L R L R L R L R L R L R L R L R L R L R L R L R L
5
Pathology
6 4
Pathology
5 3 4 4 4 2 5 4 5
Endophthalmitis
4 2 1 4
5.0 5.0 5.0 3.5 4.0 3.5 4.5
4.0
CC ST ST ST 10 ST CC CS 10 CC CS ST
1 (Perf) 5 3 4 4
4.0
CS 10 10 CS 10 CC CS CC CS
3
3.0
CS
3 3 5 4 5
3.0
10 CC ST CS CC
Pathology Pathology
1.5 4.0 4.0
4.0 4.5
Day 30
-1011 13
662
R L R L R L
4 3 6 5 5 5
3.5 5.5 5.0
CC 10 CC ST OT CS
Animal
Eye
14
R L R L R L R L
15 16 17
Energy to Rupture (trials)
Mean (R + L) (trials)
3 (Perf) 6 4
6.0
Rupture* Pattern 10 CC ST
4.0
Pathology Pathology 3 (Perf)
5 3
4.0
CS CC ON
4.0
ST 10 10 CC
Day 90
1 2 3 4 5 6 7 8 9
4 (Perf) 4 (Perf) 4 4
R L R L R L R L R L R L R L R L R L
Pathology
4 5
4.0
ST CC
5.0
Old scar Infection 3 (Perf)
5 3
4.0
Pathology
4.0
4 7 5
6.0
4 (Perf) 4
4.0
10 CS CS (CC CC (CC CS 10
+ CS) + CS)
Rupture patterns: * CC = cut-to-cut, CS = corneoscleral, ST = stellate, 10 = incisionopening, ON = optiC nerve avulsion, OT = other, CC + CS = cut-tocut with corneoscleral extension (statistically counted as 1f2 CC and 1f2 CS). See text for descriptions.
In the group of control eyes, 58% ruptured in a radiating corneoscleral pattern. Most of the remaining eyes ruptured with optic-nerve avulsions (33%), which were Table 2. Distribution of Specific Injuries Control Rupture Pattern "Cut-to-cut" Corneo-scleral Incision opening Stellate OptiC nerve avulsion Other Total
Experimental (All Groups)
No.
%
No.
%
~
0
0
15
33
,
-
7
58
12
26
-
0
0
8
17
0 4
0 33
9
20 2
8
1
2
99%
46
100%
Example
0/ ,' © /
@
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12
LARSON, et al •
QUANTITATED TRAUMA
B
au ~
:l IQ,
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>= CJ ~
au Z au
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Control
"
Injury
Incidence/ Total
Lens/vitreous avulsion Iris-root dialysis Iris prolapse
7/12 5/12 1/12
-- - - - ---~ ~
4
m
:l
Table 3. Distribution of Miscellaneous Injuries
L...--t-...., r--+-,+-b---31I-o----------1~o <5
%
Incidence/ Total
%
15/46 17/46 9/46
33 37 20
58 42
8
Note. Essentially 100% develop corneal abrasions; essentially 100% develop gaping of keratotomy incisions.
~
z a
u
DAYS POST OPERATIVE
Fig 3. Graph of energy to rupture vs. time. Each dot represents the mean of right and left eyes when both eyes were available.
rare in the experimental group (2%). One control eye ruptured with an isolated scleral laceration (8%), which did not occur in the experimental group. Other miscellaneous ocular injuries were observed frequently in both experimental and control groups and are listed in Table 3. Essentially all operated eyes developed gaping of corneal incisions, which increased after successive trials. The gaping progressed in many eyes to grossly visible lamellar corneal stromal dissection extending away from the base of the corneal incisions. In some cases, this dissection was manifested by the appearance of large sheets of corneal tissue folded back on itself. ENERGY REQUIRED FOR RUPTURE
All analyses and graphs presented here use the average of right and left eyes for a given animal when both eyes were available here. The energy required for ocular rupture in the various experimental groups over the 90-day study is graphically illustrated (Fig 3). The logarithmic scale along the "Y" axis corresponds to the number of trials of doubling energy which were required for rupture. The control group required a mean of 5.57 trials (3.2 joules) to rupture. When all experimental groups were combined, they required a mean of 4.46 trials to ruptur~, 46% of the control energy (P < 0.001). Each of the four groups was also compared individually with the control group, and the differences are shown in Table 4 and Figure 3. The day 1 and day 10 groups were found to require significantly less energy to rupture as compared to the control group (Dunnet's method of analysis). The day 30 and day 90 groups were found to require a reduced energy compared to the controls. Because of the small number of animals used in this study, a real difference was strongly suggested but not statistically significant. The wound strength for each of the postoperative intervals was similar.
CORNEAL MICROPERFORATIONS
Six eyes of five rabbits had single corneal microperforations during surgery. A macroperforation occurred in a sixth rabbit. These eyes were excluded from all previous analyses and are described separately. The six animals in this group required from one to four trials for rupture to occur, with a mean value of 3.0 trials. This represents less than 50% of the energy required for rupture of the operated eyes without perforation (mean of 4.13 trials, range of 1.5-6.0 trials). This difference was significant (P = 0.02, t-test). Eyes traumatized following radial keratotomy were studied histologically. Three patterns of corneal injury prevailed in all four of the operated groups. "Wound gape," in which the wound margins separated for the entire depth of the incision (Fig 4), was the earliest pattern identified prior to perforation. In the second and more progressive pattern, "lamellar dissection," a wound gape was seen in association with a horizontal dissection (or splitting in lamellar fashion) of corneal stromal fibers away from the base of the incision. The inner fibers and Descemet's membrane remained intact (Fig 5). The third pattern, corneal perforation, was seen as an exten~ sion of the previously described patterns. In each case of perforation, an area of wound gape and lamellar dissection was identified. In addition, an area of perforation through the remaining inner corneal fibers was also demonstrated (Fig 6). The perforation has been noted to occur at any point along the area of lamellar dissection, not necessarily in direct line with the radial keratotomy incision. Corneal perforations of traumatized normal Table 4. Energy to Rupture vs Time Group
Energy to Rupture (joules)
% of Control
P
Control Day 1 Day 10 Day 30 Day 90
3.2 1.4 0.8 1.7 1.7
100 43 25 54 52
<0.05 0.01 0.1 >0.05
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-.- . Fig 4. Wound gape: separation of wound edges following lesser trauma.
Fig 5. Lamellar stromal dissection: with additional trauma, wound gape typically develops a lamellar split of stromal fibers away from the base of the wound.
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Fig 6. Corneal perforation. Only one of the wound edges is shown. After wound gape progressed to lamellar dissection, additional trauma perforated Descemet's membrane well away from the original wound gape.
eyes without radial keratotomy showed jagged or frayed edges of lamellar fibers throughout the entire depth of the perforation (Fig 7). There was no significant lamellar dissection of corneal stroma in control eyes.
DISCUSSION This study evaluated the relative risk of blunt trauma to rabbit eyes following radial keratotomy, over a period of 90 days. Significant differences were found between eyes with radial keratotomy and controls with regard to energy requirement for rupture and patterns of injury. Rabbit eyes required 54% less energy for rupture following radial keratotomy (P < 0.001). The energy required for rupture; did not vary significantly over the 90day study (Fig 3). When microperforations occurred during the procedure, this further reduced the subsequent energy required to rupture by an additional 50% (P = 0.02). This suggests that corneal microperforation may represent a significant operative complication and should be avoided.
Precise measurement and mapping of corneal thickness before and during surgery is essential to help prevent such perfon~tions. Protective eyewear in the postoperative period may be of benefit in some patients. The patterns of rupture varied significantly between control eyes and eyes that had undergone radial keratotomy. Ninety-eight percent of the operated eyes ruptured along one or more corneal incisions, with or without extension along the sclera. Optic nerve avulsions were common in the control group (33%) and rare in the keratotomy group (2%). This observation raises the question as to whether the corneal incisions may act as protective release valve against more serious injury. Operated eyes were studied histologically following various degrees of trauma. The following progressive corneal injury patterns were found: wound gape, wound gape plus lamellar corneal stromal dissection, and eventual perforation in conjunction with the above patterns. Control eyes did not demonstrate this progression. A direct correlation of this paper with the human risk of trauma is not possible for a variety of reasons. These include rabbit corneal differences, the use of enucleated eyes, and the effect of repeated trauma to individual eyes. 665
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Fig 7. Corneal perforation in, a control eye shows frayed edges of the wound throughout the entire depth of the perforation. No significant lamellar stromal dissection is seen.
The rabbit cornea varies anatomically with the human cornea. 5 The rabbit cornea has a larger diameter and is thinner in depth. Bowman's membrane in the rabbit is thinner and is difficult to identify without electron microscopy. The rabbit endothelium is also capable of regeneration. The rabbit, therefore, provides a poor model for study of endothelium and Descemet's membrane, which was not attempted. Trauma was applied to enucleated eyes to isolate specifically the ocular resistance to rupture. The protective effects of the orbit, including compressible fat and the potential for blowout orbital fractures, were thereby eliminated. This would be likely to modify the energy required for rupture and possibly the resultant ocular injuries. Traumatic energy was delivered in repeated, doubling doses to individual eyes until rupture occurred. This conserved the number of animals required for study but may have modified both the energy required for rupture and the resultant injuries. The ocular injuries created in this study differ from previously reported human series of ocular rupture. Cherry reported on 34 cases of blunt trauma resulting in rupture of the globe.6 Isolated limbal and scleral lac-
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erations accounted for 89% of his cases. None were present in our radial keratotomy group, and only 8% occurred in our control group. Isolated corneal lacerations did not occur in his patients, whereas 72% of our operated rabbit~ and none of our controls ruptured as isolated corneal patterns. Cherry described corneoscleral lacerations in 11 % of patients, as compared with our operated group (26%) and controls (58%). Optic nerve avulsions did not occur in his series. These results suggest a shift away from limbal or scleral ruptures toward corneal lacerations. This may be due to the presence of the incompletely healed corneal incisions or due to the method of trauma used in this study delivering the greatest energy to the recipient cornea in a manner different from most commonly encountered human blunt trauma. Further studies are warranted to evaluate better the trauma risk following radial keratotomy. Primate eyes would better approximate the human globe. Future similar studies should use one eye for each animal as a control. It became evident that right and left eyes of a given animal required similar degrees of trauma to rupture. A more prolonged study period is needed to more accurately reflect the long-term resistance to trauma.
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ACKNOWLEDGMENT Statistical analysis was provided by Hyman Menduke, PhD, Thomas Jefferson Medical College, Philadelphia, Pennsylvania.
REFERENCES 1. Fyodorov SN, Durnev W. Operation of dosaged dissection of corneal circular ligament in cases of myopia of mild degree. Ann Ophthalmol 1979; 11 :1885-90.
QUANTITATED TRAUMA
2. Schacher RA, Levy NS, Schachar L, eds. Refractive Modulation of the Cornea. Proceedings of the Kerato Infractive Society Meeting on Radial Keratotomy and Keratorefraction. Denison, TX: LAL Publishing Co., 1981. 3. Bores LD, Myers W, Cowden J. Radial keratotomy: an analysis of the American experience. Ann OphthalmoI1981; 13:941-8. 4. Hoffer KJ, Darin JJ, Pettit TH. UCLA clinical trial of radial keratotomy; preliminary report. Ophthalmology 1981; 88:729-36. 5. Prince JH. The Rabbit in Eye Research. Springfield, IL: Charles C Thomas, 1964; chapter 6. 6. Cherry PM. Rupture of the globe. Arch Ophthalmol 1972; 88:498-
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