ENDOPHTHALMITIS
373
3. Ballantyne, J. F., and Quigley, J. H. : Antibiotic sensitivities of staphylococcus aureus recovered from eye cultures. Tr. Canad. Ophth. Soc, 6:143, 1953. 4. Leopold, I. H: Surgery of ocular trauma. Arch. Ophth., 48:738, 1952. 5. Halliday, J. A., and Ormsby, H. L.: Carboniycin in ocular infections. Am. J. Ophth., 39:51, 1955. 6. Querengesser, E. I., and Ormsby, H. L.: Ocular penetration of erythromycin. Canad. M. A. J., 72: 200, 1955. 7. Naib, K., Hallet, J. W., and Leopold, 1. H.: Observations on the ocular effects of erythromycin. Am. J. Ophth., 39:395, 1955. 8. Crabb, A. M., Fielding, I. L., and Ormsby, H. L.: Bacillus proteus endophthalmitis. Am. J. Ophth., 43:86, 1957. 9. Cook, C, and MacDonald, R. K. : Effect of cortisone on the permeability of the blood aqueous barrier to fluorescein. Brit. J. Ophth., 35:730, 1951. 10. Hogan, M. J.: Postoperative infection after cataract. Tr. Am. Acad. Ophth., 61:33, 1957.
CHEMICAL BURNS O F T H E EYES T R E A T E D W I T H EGG MEMBRANE* A N EXPERIMENTAL STUDY ANTONIN H E I N C ,
M.D.
Olomouc, Czechoslovakia
Burns of the eye are severe injuries which often result in visual loss or destruction of the eye. For this reason clinical observations and extensive experimental work have been carried out. The first reports described the clinical course of this injury and tried to determine the most suitable conservative treatment to be used for secondary compli cations due to ocular burns. Denig's sug gestion (1912) brought a complete change of the existing therapy and introduced the surgical treatment of chemical burns of the eye. This is, of course, a very trying and laborious treatment. Therefore, ophthalmolo gists are constantly on the alert for simpler and more efficient methods of treatment. However, since new suggestions do not al ways meet the requirements defined by con trolled experiments, the suggested procedure may prove to be harmful. When treating chemical burns it must be remembered that the burned tissue contains a considerable amount of the caustic which penetrates from the area of the highest con centration (in the upper layers of the surface tissues) in all directions into the adjacent * From the Department of Ophthalmology of the Medical Faculty of the Palacky University, Olo mouc (Director: Prof. Dr. V. Vejdovsky).
regions where lower concentrations are pres ent. In the eye it penetrates into the subconjunctival tissue, the sciera, the inner structures of the eye, and into the cul-de-sac. Even after flushing the conjunctival sac, caustic is still found in a concentration capa ble of producing further burns. It has been proven by Neuman7 that Denig's plastic sur gery of the burn is of particular importance because it prevents penetration of the caus tic into the depths, and Heine 5 · 6 has pointed out that by this means secondary burns of the eye, and particularly of the cornea, could be avoided. In 1936, O'Connor 2 observed that burned conjunctiva of the eyelid may impair the condition of the cornea and he recommended covering the conjunctiva of the eyelid with a mucous graft. His work did not meet with response, though the idea was good. In 1941, Brown 1 observed the same phenomenon. He surmised that it is the constant contact of the cornea with the inflamed conjunctiva and the irritation of the cornea rather than ac cumulated caustic which produces opacification, and recommended separation of the opposing injured conjunctival surfaces by inserting rabbit peritoneum. Sorsby and Symons9 modified this method
374
ΑΝΤΟΝίΝ HEINC The methods of Brown and the Crolls have also found their disciples in our coun try, but since I do not consider the method to be adequate I have accumulated experi mental proof to support my view. EXPERIMENTS FIRST SERIES
Fig. 1 (Heine). Rabbit 33. After covering the cornea with an egg membrane a patch was sutured to the adjacent skin of the right eye. by covering the burned tissues with an amniotic-membrane graft instead of rabbit peri toneum. Later Sorsby, Haythorne, and Reed10 modified this method by using amniotic membrane to cover the conjunctiva only, but not the cornea. A further modification of Brown's initial method was introduced by Croll and Croll.3 They utilized egg membrane to cover the cornea and even filled the cul-de-sac of the conjunctiva with it. Even though I do not con sider Brown's method justifiable it must be admitted that peritoneum and amnion could be useful in that they absorb some of the caustic. This possible advantage does not hold true with egg membrane which appears to be inert to ordinary caustics. However, these methods may even be harmful for they disregard the basic principle of treatment ac cording to which the caustic has to be re moved from the eye as quickly and as thoroughly as possible. It would seem that these methods might even impede the nat ural washing away of the caustic from the eye. These methods return to the closed treatment of burns, though nowadays the open treatment of burned eyes is more and more the method of choice (that is, the tears are given opportunity to wash most of the noxious substances from the eye).
In the first series of experiments the pri mary concern was to find out if it is possible to fix egg membrane to the eye and whether application produces corneal defects (table 1). For that purpose, 10 rabbits were sub jected to a total of 14 experiments. Merely covering of the eye with egg membrane pro duced some difficulties for the rabbit pawed the membrane from its eye within a short time even as it did when the egg membrane was sutured to the conjunctiva. Therefore, there had to be some procedure to protect the eye from the paw of the rabbit. At first the eyelids were sutured in one or two places ; later on, the eye was covered with a patch (fig. 1) or an acrylic shell which was not held by the lids but was sutured to the adjacent skin of the eye. These tech niques did not produce any pathologic changes in the eye (Experiments 3 and 11). A tiny contact prosthesis made of acrylic and molded to conform to the cast taken from the eye with Zelex was also tested. Even though the prosthesis was one or two mm. deeper than the cornea, merely applying it resulted in minor lesions and corneal opac ities. This was, perhaps, due to not being able to mold the prosthesis individually, for the taking of the cast produced corneal de fects and the rabbit had to be removed from the experiment for some time. Erosions and corneal opacities were more frequent when egg membrane was in serted under the prosthesis (Experiments 4, 5, and 6). Therefore, the use of egg mem brane with the contact prosthesis was re jected. It was necessary to find another way to apply the egg membrane to the eye, for simply covering the cornea was unsatisfac tory even though the eyelids were sutured.
TABLE 1 CHEMICAL BURNS OF THE EYES TREATED WITH EGG MEMBRANE Covering of the Eye
Exper iment Rabbit No.
Eye
Methods Employed
Re moved (days)
Condition of the Cornea
Egg Membrane 1st day
2 day
4 day
3 day
6 day
Application on the Cornea
Re moved (days)
CO
FL
CO
FL
CO
FL
CO
FL
Notes
CO 1 F L
Day
CO
FL
1
31
D
Suture of the eyelids
2
Only laid on
2
-
-
Θ
Θ
-
-
-
-
-
-
-
-
-
Egg membrane lost from the eye
2
30
D
Suture of the eyelids
2
Only laid on
2
-
-
+
+
-
-
-
-
-
-
55
±
Θ
Egg membrane folded in the lower cul-de-s c
3
29
D
Suture of the eyelids
1
Θ
—
Θ
Θ
-
-
-
-
-
-
-
-
-
-
-
4
28
D
Contact prosthesis
1
Θ
—
+
±
-
-
Θ
Θ
-
-
-
-
-
5
28
S
Contact prosthesis
3
6
28
D
Contact prosthesis
4
7
27
,
S
1 Suture of ' the eyelids
8
27
!
D
9
32
'
10 11
—
-
-
-
-
±
±
(Contact prosthesis)
4
-
-
-
-
-
-
3
Acryl ring
3
+++ +++ -
-
Suture of the eyelids
1
Acryl ring
1
D
Caoutchouc shell
2
Acryl ring incomplete
2
-
-
28
D
Suture of the eyelids
2
Conjunct! val sutures
2
-
-
++
31
S
Caoutchouc Shell
1
Θ
—
Θ
Θ
Θ
++ ++
12
3i
D
Caoutchouc shell
1
Conjunctival sutures
1
++
+
13
35
S
Caoutchouc shell
1
Conjunctival sutures
1
-
+
14
36
D
Acryl shell
2
Conjunctival sutures
2
-
-
++ ++
-
+++ +++ ++ ++ ++
_
1
I
-
Corneal infiltration
+
17
++
Θ
Pronounced vascularization of the cornea
-
14
+
+
Corneal infiltration
16 i + +
Θ
Corneal infiltration
Θ
Θ
+
-
-
+++ +++ -
-
-
-
++ ++
+
-
-
-
-
~ i "
13
-
-
-
-
-
-
-
-
-
-
—
—
—
—
++
+
14
+
Θ
+
+
-
—
—
-
12
+
Θ
-
CO = Corneal opacity over + 1/4, + + 2/4, + + + 3/4, + + + + 4/4 of the area. FL = Corneal staining withfluoresceinover + 1/4, + + 2/4, + + + 3/4, + + + + 4/4 of the area.
-
—
g
_
+
-
X
-
- ! - ! _
Γ)
-
—
\
n > r
60 G W
in O
m «;
fr; t/i
Egg membrane overlapping the eye (sutured only in the upper area of the conjunctiva)
TABLE 2 CHEMICAL BURNS OF T H E EYES TREATED WITH EGG MEMBRANE
Rabbit No.
Eye
Con Egg Membrane junctiva with a Covering Re Limebum the Con moved (minutes) junctiva (days)
37
S
Θ
yes
38
D
5
Θ
38
S
7
yes
39
D
7
Θ
39
S
7
yes
40
D
7
Θ
40
S
7
41
D
41
3
4
Condition of the Cornea 1st day
2 day
CO
FL
CO
FL
CO
FL
Θ ±
Θ
-
-
Θ
Θ
+ + + + + ±
-
3 day
4 day
5 day
6 day
7 day
8 day
9 day
10 day
CO
FL
CO
FL
CO
FL
CO
FL
CO
FL
CO
FL
CO
FL
Θ
Θ
-
Θ
Θ
-
-
Θ
+
Θ ±
-
+
Θ ±
Θ
+
Θ ±
+
+
±
Θ ±
Θ
18
+ ±
-
-
IS
±
15
+
Θ Θ
Θ
Θ
13
Θ
Θ
+ +
13
+ ±
Corneal infiltration, pronounced vascularization
—
16
+ Θ
Graft adheres to the cornea. After re moval of the membrane enlargement of the extent of t h e defect
-
16 23
Θ ±
Θ Θ
23
±
Θ
11 11
Θ Θ
Θ Θ
Θ
-
-
± ±
Θ ±
-
-
± ±
Θ ±
Θ ±
±
Θ
Θ
-
-
Θ
Θ
+
-
Θ
+ ±
-
Θ
5
yes
7
+ + + +
—
—
+ + ~ — — — + + + + + + ~
Θ
yes
4
Θ
±
10
yes
9
-
Θ
D
+ + + + -
-
-
42
S
Θ
yes
9
±
±
yes
10
S
42
-
±
Θ ±
Θ ±
Θ
- - - - Θ Θ Θ Θ Θ Θ + + + + + + - - + + ± ± + + + + + +
43
D
10
yes
4
+
+
+
±
+
+
±
±
Θ
yes
6
±
±
Θ
Θ
Θ
Θ
Θ
±
Θ
Θ Θ
-
S
44
D
10
yes
7
±
+
±
±
±
±
±
±
+ +
44
S
Θ
yes
7
Θ
Θ
Θ
Θ
Θ
Θ
Θ
+
±
-
Θ Θ
-
+ + + +
43
-
± ±
-
-
CO ««Corneal opacity, + marked, ± mild, Q without opacification, — not controlled. FL = Corneal staining with fluorescein, + distinct, ± mild, © the cornea does not stain,
-
-
±
-
± Θ
■ not controlled.
±
Θ Θ
± Θ
Θ Θ
Θ
18
± ±
±
FL
Θ
±
± ± ±
CO
+ ±
±
6
Notes
day
-
-
+ ±
—
—
—
—
—
~ Θ Θ
—
—
—
—
—
—
On the 1st d a y t h e egg membrane covered \ of the cornea—the portion covering the cornea was cut-off. Corneal infiltration (?)
After removal of t h e membrane en largement of the extent of the defect
T h e membrane adheres to the cornea T h e membrane adheres to the cornea, a t the end of t h e 5th day t h e entire membrane turns down a n d hangs over t h e cornea
At the end of t h e 3rd d a y the mem brane is turned down a n d hangs over the cornea. At the end of the 6th d a y the membrane is kept in place by one suture At the end of t h e 6th d a y the mem brane turns down and hangs over t h e cornea At t h e end of the 4th d a y the mem brane is turned down a n d hangs over the cornea
> O
X
m o
CHEMICAL BURNS OF EYES The membrane either was extruded from the eye or it was found folded up in the culde-sac (Experiments 8 and 9). Even then one of the experiments resulted in corneal de fects. Fixing the egg membrane to the eye with an acrylic ring, molded to conform to the cast taken from the conjunctival sac and having a large aperture for the cornea to avoid damage due to pressure, was also tried. The ring itself did not produce any patho logic changes of the cornea but, when it had to hold the egg membrane in place, there al ways appeared major or minor corneal de fects. The use of a ring with an opening for the palpebra tertia (membrana nictitans) did not improve the results. Therefore, the egg membrane was laid over the cornea and su tured to the conjunctiva. In my opinion, how ever, this method of application is not suit able, particularly in ocular burns, for the suture necessarily results in trauma to an already damaged eye. In these experiments (10, 12, 13, and 14) I always encountered more or less severe corneal defects and opacification. From the first series of experiments it may be concluded that egg membrane is not a suitable material for protection of the cor nea in burns of the eye, for any trauma to the cornea impairs the condition of the burned eye. Trauma must be prevented at all costs so as not to make the matter worse. Experiments have shown that the egg mem brane acts as a foreign body on the cornea and that its rigidity injures the cornea over and over again. Also, in the course of these experiments, infection of the cornea was ob served three times, though the rabbit is con sidered to be rather resistant to infection. Slower circulation of tears under the mem brane may have given rise to infection, for work with rabbits cannot be carried out under aseptic conditions. However, this ob servation speaks against covering the cornea with egg membrane. It may also explain why, in their second report, Sorsby, Haythorne, and Reed10 speak of covering only the
377
burned conjunctiva with an amniotic-mem brane graft, leaving the cornea uncovered. SECOND SERIES
In spite of these negative results, I hoped it was possible to find a way to utilize egg membrane in chemical injuries of the eye. I wondered if the egg membrane was capable of separating the burned conjunctiva from the intact or less injured structures of the eye, thus preventing secondary burns of the cornea. This problem was investigated in the second series of experiments (table 2). In the Rabbit 37 a portion of egg mem brane was sutured to the conjunctiva; this time no injury to the cornea was observed. In three rabbits (38, 39, 40) lime-burns of the conjunctiva were produced in the upper margin of the limbus of both eyes in an area five by nine mm. The lesion in the left eye was covered with egg membrane ; the right eye remained without therapy. In Rabbit 38 the egg membrane covered not only the con junctiva but also the upper third of the cornea. A portion of the egg membrane hanging down over the cornea was cut off 24 hours after infliction of the burn. The area of the cornea which had been covered with egg membrane was opaque and stained deeply with fluorescein. The extent of the defect and the corneal opacity receded con siderably during the following days but it was perceptible, even though no traces of a burn could be seen on the cornea of the right eye. On the sixth day pronounced vascularization developed in the left eye. A similar difference in healing was also noted with the Rabbits 39 and 40. A narrow strip of cornea in the right eye of Rabbit 39 was also burned but the resulting opacity had cleared to a great extent during followup; no corneal defect was noted after the fourth day. In these rabbits the egg mem brane was found folded up (figs. 2 and 3) due to chemosis in the adjacent area of the burned conjunctiva and it adhered more or less to the cornea. In order to find out the various corneal
378
ΑΝΤΟΝίΝ HEINC cularization developed in the opaque areas of the cornea. Although this vascularization progressed quickly, it disappeared quickly as well, for on the 23rd day, practically no vascularization was found. A similar clini cal course could be observed in the left eye
of Rabbit 44.
Fig. 2 (Heine). Rabbit 43. The burned conjunc tiva of the right eye was covered with egg mem brane. Due to the cliemotic conjunctiva the egg membrane folded up and did not remain in contact with the conjunctiva. Photograph taken immediately after operation. changes produced by the contact of the mem brane with the corneal surface, burns were produced in the right eyes only of four more rabbits and approximately similar portions of egg membrane were sutured to the con junctiva of both eyes. In the intact eye the egg membrane remained quite well in place, for there was no chemosis of the conjunc tiva, or it only slightly involved the cor nea, as may be seen from the results obtained in Rabbit 4 1 . In the further experiments, the egg membrane was turned down and left hanging over the cornea after the conjunctival sutures were loosened. In Rabbit 42 the egg membrane adhered slightly to the cornea of the left eye. On the fifth day the conjunctival suture loosened and the whole mem brane could be seen lying on the cornea around the episcleral suture. The adhering membrane had produced a slight indentation on the cornea, and the cornea under it was slightly opaque. At the end of the second day, half of the adhering membrane was cut off. T w o days later, the cornea under the remaining adhering portion of the membrane still stained considerably with fluorescein and, in the areas where the membrane had been cut off, the cornea was epithelized but opaque. That this meant more than a defect of the epithelium seemed verified at the end of the ninth day when a pronounced vas-
It is interesting to follow the progress of changes in the burned eyes which had been covered with egg membrane. In Rabbit 44, the conjunctival suture was loosened at the end of the sixth day, and the membrane was inverted and hanging over the cornea around the episcleral suture. O n the injured cornea, the egg membrane produced a deeper opacification and aggravation of the epithelial defect. On removing the egg membrane from the burned conjunctiva the findings were always the same. Within a short time—in some min utes up to half an hour—an enlargement of the defect on the cornea and a deepening of the corneal opacity could be observed, evi dently due to an accumulation of the caustic under the membrane from the necrotic burned conjunctiva which, when liberated, acts as a corrosive agent at the time when, with conservative treatment or eventually without treatment, the washing away of the caustic from the surface of the eye would have been completed. That the egg membrane
Fig. 3 (Heine). Rabbit 43. Same as Figure 2 but taken about a half-hour after operation.
379
CHEMICAL BURNS OF EYES
does not satisfactorily separate the cornea from the burned conjunctiva is demonstrated by the fact that a comeal defect results not only at the place where the egg membrane adheres to the cornea but also in the adjacent area. COMMENTS
These two series of experiments show that egg membrane has no effective power in the treatment of caustic burns of the eyes be cause: 1. The egg membrane is not inert so it reacts to the surface of the cornea. It prob ably mechanically produces denuding of the cornea which makes it possible for even minute amounts of the caustic to produce comparatively deep opacifications. 2. Under the egg membrane tear circulation is only slight or nonexisting. The tears have a bactericidal effect and lack of tearing prob ably predisposed to corneal infections the rabbits used in these experiments, since rabbits are known to be rather resistant to infection. 3. The egg membrane does not separate the burned tissue from the intact one. Under the membrane the caustic accumulates in a comparatively high concentration and then penetrates into the capillary spaces between the membrane and the surface of the eye. Eventually, folds in the egg membrane, due to the rigidity of the membrane, may facili tate this penetration. 4. The egg membrane does not absorb the caustic but causes it to deposit in higher concentrations, consequently the caustic may penetrate into the depths and, when the mem brane is removed, it is washed away in a higher concentration into the conjunctiva! sac and has a further caustic effect. 5. The egg membrane cannot act as a bio logic stimulator for it is not absorbed. For these reasons, the treatment of chemi cal burns by egg membrane should be re jected. In such cases the egg membrane may even have an aggravating effect, for it pre vents the natural washing away of the caus tic from the eye, thus disregarding the basic
principle of treatment—that the caustic must be removed from the eye as quickly and as thoroughly as possible. On persuing the reports published on egg membrane, it may be seen that the results are far from ideal. Croll and Croll3 report two failures in a total of 26 treated cases (about eight percent). Among 14 patients treated (the majority of cases) there were only minor or moderately severe burns, the prognosis for which was relatively good. The Crolls have some followers. In our country Pitter 8 refers to this method. He reports successful results by this method but, again, only minor or com paratively moderate burns with a good prog nosis were treated. It has been possible to observe several cases in other departments which were treated with egg membrane. The results speak uniformly against the use of the egg membrane for burns of the eye. One of these cases is here reported: CASE REPORT
Patient S. P. (No. 938/1957). On September 21, 1956, mortar splashed under pressure into his left eye. He immediately irrigated his eye with water and was transferred to a nearby hospital where, within an hour after the accident, he was treated according to Croll's method. On November 15th, the patient was treated at the Department of Oph thalmology of the Palacky University in Olomouc.
Fig. 4 (Heine). S. P. aged 31 years, living at N., record No. 938/57. Following a lime burn, the left eye was treated according to the Crolls' technique within half an hour. Condition two months after the accident. Symblepharon, leukoma, vascularization and corneal abscess. Vision, perception of light with inaccurate projection.
380
ANTONIN HEINC
The findings were partial symblepliarons of both upper and lower eyelids, total leukoma with an abscess forming in the center of the cornea, and a pterygiumlike circular vascularization (fig. 4). Vision was light perception with inaccurate projection (bulbus mollis).
It would seem that even conservative treatment so soon after the burn should give better results. Further, Denig's plastic oper ation was probably indicated, as evidenced by the rather wide symblepharons, particu larly on the upper eyelid. Several other cases which show similar re sults have been observed. Therefore, I have never made use of this method and, on the basis of the experimental results, I shall never employ it. The long silence since other authors published the results of this method (Brown 1941 ; Sorsby, Haythorne and Reed 1947; Croll and Croll 1952) would seem to demonstrate that further experiences have not been the best. Both the experimental and the clinical ob servations speak clearly against the use of egg membrane and against all methods of covering the burned cornea in treating chem ical injuries of the eye. In these cases, the
theoretical considerations and aims have been to prevent secondary burns of the cor nea but the authors have failed to take into account other circumstances which, both clinically and experimentally, prove to be fatal. The reported cases showing positive results merely demonstrate that the eye can heal quite promptly even under most un favorable conditions. This has led to errone ous interpretation of the results of the treat ment. SUMMARY
In the first series of rabbit experiments, it was shown that egg membrane in the conjunctival sac acts as a foreign body and pro duces corneal defects. The second series of experiments fur nished proof that the egg membrane holds the caustic on the surface of the eye in considerable concentration ; subsequently this produces a secondary burn of the eye. The egg membrane also prevents the natural washing away of the caustic by lacrimation. Department of Ophthalmology, Palacky University.
REFERENCES
1. 2. 3. 4.
Brown, A. L.: Arch. Ophth., 26:754, 1941. O'Connor, G. B.: Rev. chir. struct., 6:273, 1936. (Ref. Zentralbl. ges. Ophth., 37:436, 1937.) Croll, M., and Croll, L. J.: Am. J. Ophth., 35:1585, 1952. Denig, R.: Munch, med. Wschr., 59:579, 1912. Heine, A.: Cs. Of thai., 12:65, 1956. Cs. Of thai., 11:250, 1955. Neuman, J.: Klin. Monatsbl. f. Augenh., 95:491, 1935. Pitter, J.: Cs. Of thai., 12:59, 1956. 9. Sorsby, A., and Symons, H. M.: Brit. J. Ophth., 30:337, 1946. 10. Sorsby, A., Haythorne, J., and Reed, H.: Brit. J. Ophth., 31:409, 1947.