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Effect of Steroids on Tensile Strength of Corneal Wounds*
TRANQUILIZING AGENTS
759
16. Green, H., et. al.: Research Department, Wills Eye Hospital. Unpublished results. 17. Boudet, M., and Viallefont: Reported in Arch. Ophth., 54:793-794 (Nov.) 1955. 18. Ahmad, S. S.: Research Department, Wills Eye Hospital. Personal communication. 19. Wien, R., and Mason, D. F. J.: Pharmacology of M and B 2050. Lancet, March 7, 1953, pp. 454-455. 20. Waldman, S., and Pelner, L. Treatment of the ambulatory hypertensive patient with Pentolinium tartarate. Am. J. M. Sc, 231:140-150 (Feb.) 1956. 21. Clinical research report on Ansolysen. Wyeth Laboratories, Philadelphia.
E F F E C T O F STEROIDS ON T E N S I L E S T R E N G T H O F CORNEAL W O U N D S * A U S T I N I. F I N K ,
M.D.
Brooklyn, New York AND IRVING BARAS,
M.D.
New York INTRODUCTION
Cortisone has proven to be a useful ad junct in the treatment of certain inflamma tory eye diseases.1 However, this drug was initially not fully exploited in inflammatory processes following surgery because of early reports in the literature describing the inhibi tion of wound healing by cortisone.2"6 The majority of these reports were based on histologic studies,2-4-8 and conclusions as to tensile strength were merely inferred. In a recent article, Palmerton 7 reported that cortisone has an inhibitory effect on corneal wound healing. He made use of a technique whereby he measured directly the tensile strength of the wound. This technique was similar in many respects to one which we employed in measuring the effect of corti sone on corneal wound healing. The study which was carried out in 1952-53 and pre sented to the Eastern Section of the Associa tion for Research in Ophthalmology in February, 1954, demonstrated no such in hibitory effect by cortisone. The difference ♦From the Department of Surgery (Ophthal mology) of the Cornell University Medical College. Presented before the Eastern Section of the As sociation for Research in Ophthalmology, February, 1954, Philadelphia, Pennsylvania.
in conclusions might be attributed to certain fundamental variances in technique: a. No mention was made by Palmerton of the use of anticoagulants for the preven tion of clotting of the rabbit aqueous by the fibrinogen contained therein. A fibrin would have a tendency to become interposed be tween the lips of the wound and thus prevent consistent cornea-to-cornea wound approxi mation. More pronounced variability could thus be expected. b. The length of the corneal wound em ployed by Palmerton was five mm. We had tried a wound of this size and discarded it as unsatisfactory. It was our experience that a seven-mm. corneal incision afforded us a more accurate bursting point. c. Our traction sutures were placed at the time of surgery, while Palmerton placed his at the time of testing. We felt that trauma to the cornea and distortion of the wound edges would occur if traction sutures were placed just prior to measuring the bursting point of the wound. One cannot adequately estimate to what extent this added manipulation has impaired the solidity and therefore the ten sile strength of the wound. Another factor of variability has thus been introduced. d. We would like to point out that there
760
AUSTIN I. FINK AND IRVING BARAS
was a considerable difference in the method of administration of the cortisone. Palmerton mentions the use of both topical and subconjunctival cortisone, whereas we em ployed the intramuscular route. We make no attempt to correlate differences as a result of this particular variation but wish to men tion that it existed. We feel that these differences have enabled us to obtain a more accurate evaluation of the tensile strength of the wound. Our ad ditional clinical experience in recent years with cortisone in patients following cataract extraction and corneal grafting supports the conclusions drawn in our paper. We there fore feel that reporting of our thus far un published work may be of value in shedding further light on this controversial question. METHOD TECHNIQUE
A corneal incision of specified length was made. The wound edges were then pulled apart after a certain number of days. The quantity of force found necessary to ac complish this disruption was then used as a measure of the tensile strength of the wound. A seven-mm. linear scratch was made in the center of the cornea to outline the posi tion of the corneal incision. Two intracorneal sutures were then placed four mm. on either side of the scratch. They ran through the cornea for a distance of approximately five mm. and were tied with a short loop. These loops were to be used later as points of fixation for disrupting the corneal wound. A Stallard-type suture, three mm. in length, was placed so as to straddle the cen ter of the corneal scratch. The loop of this center suture was then pulled aside, and a seven-mm. incision was made with a Wheeler knife at the site of the previous corneal scratch (fig. 1). The anterior chamber was then irrigated with 2.5-percent sodium citrate in order to prevent clotting action by the fibrinogen contained in the rabbit aqueous. If this were not done, a fibrin clot might become inter-
Figs. 1 and 2 (Fink and Baras). The surgical technique. posed between the lips of the wound and thus prevent adequate approximation. The Stallard-type suture was then pulled taut and tied to re-approximate the wound edges (fig. 2). Atropine sulfate (50 percent) was then instilled in the eye followed by penicillin ointment (500 [Ag.). The lids were then sutured together. After a specified period of time, varying from three days to a week, the wounds were disrupted. This was accomplished by at taching a tiny hook to each of the preplaced intracorneal loop sutures. The Stallard suture was then cut. The hooks were then attached to strings which ran over pulleys and were in turn connected to a weighting pan. BB shot was then slowly added to the weighing pan until the wound edges separated and aqueous was lost (fig. 3). The pan and BB shot were then weighed arid this figure was recorded as a measure of the tensile strength of the wound. The rabbits were divided into two groups. One group received daily subcutaneous in jections of cortisone (15 mg./kg. of body
761
E F F E C T O F STEROIDS ON CORNEAL W O U N D S
Fig. 3 (Fink and B a r a s ) . Tech nique of wound disruption.
weight). This dosage had been used pre viously by Maumenee9 in investigating the role of cortisone in corneal graft sensitization. Cortisone was administered immediately following surgery and continued until the wound was disrupted. The second group re ceived nothing. OBSERVATIONS
Included in this study are observations made on 71 rabbit eyes. Many more eyes had been operated upon but could not be used for the following reasons: a. Intraocular infections. This complica tion was found more often in rabbits receiv ing cortisone and occurred in approximately one out of four rabbits. b. Sloughing of sutures. It was, as pre viously mentioned, necessary to place all sutures intracorneally, in order to preserve the anterior chamber and prevent premature clotting of the aqueous. The rabbit cornea is
extremely thin. This made it difficult to place the sutures intracorneally and at the same time deep enough to prevent sloughing. c. Poor approximation of the wound edges. The eyes were inspected grossly and all those with poorly approximated wound edges were discarded. The principal observation of this study was that cortisone had no significant influ ence on the tensile strength of corneal wounds in rabbits. The animals were divided into three separate groups; those with wounds which were disrupted on the fourth, the fifth, and the seventh day following sur gery. It is noted that the tensile strength of the wounds gradually increased from the fourth to the seventh day (table 1). In the first series of experiments, as dem onstrated by Table 4, the average tensile strength of the wounds in the cortisone treated rabbits exceeded that of the un treated animals. However, the technique of
TABLE 1 CORTISONE AND CORNEAL WOUND HEALING: SUMMARY OF FIRST EXPERIMENT
A Number of Eves Average Tensile Strength Standard Deviation "t" Conclusion
Four Days B
10 77 gm. 22
10 93 gm. 11
1.49 Not significant
K E Y : A: Control rabbits; B : cortisone-treated rabbits.
A
Five Days
18 98 gm. 25
Seven Days
B
A
8 105 gm. 19
10 121 gm. 29
0.64 Not significant
B
4 160 gm. 13
2.49 Nearly significant
762
AUSTIN I. FINK AND IRVING BARAS
T E N S I L E S T R E N G T H
I N
So
G R A M S
A
.5
3>"YS
*
5
&
^7
Akr
Graph 1 (Fink and Baras). Observations in studies on cortisone and corneal wound healing.
the experiment gave rise to a considerable experimental variation as evidenced by the large standard deviation. The figures were then submitted to further statistical analysis in order to determine whether the difference between the two groups was actually significant or lay within the limits of experimental error. The "t" test was used as the criterion (the letter "t" represents the ratio between the difference of the treated and untreated groups and the standard error of the difference). The four- and five-day series were then found to be not significant. The seven-day group was found to approach statistical significance. A second series of seven-day studies was therefore undertaken. The rea sons for further study were twofold: (a)
The cortisone-treated group in the first series was small; (b) we wished to introduce further statistical controls. This included pairing of the treated and untreated animals, with recording of weight and sex. The results in this series were then analyzed, utilizing the "t" test and the differ ence between the treated and untreated group was found not significant (table 2). DISCUSSION
The observations of this study have led us to assume that the use of cortisone does not materially affect the tensile strength of corneal wounds in rabbits. This statement would seem to be in direct variance with many previously published reports dealing with cortisone and wound healing. Ragan10
EFFECT OF STEROIDS ON CORNEAL WOUNDS TABLE 2 CORTISONE AND CORNEAL WOUND HEALING: SUMMARY OF SECOND EXPERIMENT
Number of Animals Average Tensile Strength Standard Deviation " t " test Conclusion
Control Rabbits
CortisoneTreated Rabbits
6 137 gm. 26
6 141 gm. 31
0.38 Not significant
was first to demonstrate the inhibition of wound healing by cortisone. Many papers, dealing with this subject, have been pub lished since that time. Most have agreed with Ragan's conclusion 5,6 ' 11 while others have found the steroids to be without effect in wound healing.12-15 Investigations on animals have fallen into two groups; histologic studies and experi ments in which the criterion was the me chanical bursting strength of the wound. The majority of investigators seem to agree that there is a general supression of fibroblastic proliferation in cortisone-treated animals. There have been a number of other studies in which the steroids exhibited little or no effect on wound healing. Bangham8 found that cortisone had no effect on guinea pigs but did cause retarda tion in rabbits. He attributed this to a species difference. This might also account for the lack of response, reported by Ragan 10 in cortisone-treated rats. Findlay and Homes 12 found cortisone to have no effect on wound healing in rabbits placed on a normal diet. Those with protein depletion, due to weight loss, showed retardation in healing when placed on cortisone. Ashton16 found no inhibition with this steroid when therapeutic doses were given. In larger doses there was a delay in healing. Cole and Orbison,17 experimenting with dogs, found that sutured wounds healing per primam were not affected by cortisone. They
763
point out that wound healing per primam re quires less capillary proliferation and fibro blastic response than those healing by second ary intention. Grant14 and Gonzalez15 work ing on experimental tendon repair in rabbits found no inhibition with cortisone. There has accumulated a small number of reports showing cortisone to have no effect on wound healing in man. Greene and coworkers 13 reported normal healing in corti sone-treated patients upon whom splenectomies were performed. Kay and Odell18 cite three cortisone-treated arthritics upon whom reconstructive foot operations were performed without any impairment of heal ing. Daily and Daily19 feel that the topical use of cortisone in corneal transplantation, both at the time of surgery and postoperatively, reduces the hazard of operation. Certain of the above studies deserve added comment in relation to our own observations and technique. It was our purpose to have these wounds heal by primary intention thus paralleling Cole's observations on dogs. Maintaining our rabbits on a normal diet without protein loss might have prevented a deleterious influence by cortisone. It is not the purpose of this paper to dis pute the well-substantiated histologic evi dence demonstrating the inhibition of fibro blastic proliferation in the cornea with the use of cortisone.2-16'20 However, from a re view of our observations, it would not be unreasonable to assume that there is little or no relationship between the histologic picture in a corneal wound and the actual tensile strength of that wound. CONCLUSION
Under the conditions of this experiment and in the animals tested it is our belief that cortisone seems to exert no significant effect on the tensile strength of experimentally induced corneal wounds in rabbits. 451 Clarkson Avenue (3).
REFERENCES 1. Gordon, D. M., McLean, J. M., et al.: The use of A C T H and cortisone in oohthalmoloev Am T Ophth., 34:1675-1686 (Dec.) 1951.
764
AUSTIN I. FINK AND IRVING BARAS
2. Ashton, N., and Cook, C.: Effect of cortisone on healing of corneal wounds. Brit. J. Ophth., 35 :708 (Nov.) 1951. 3. Newell, F. W., and Dixon, J. M.: Effect of subconjunctival cortisone upon the immediate union of experimental corneal grafts. Am. J. Ophth., 34:977 (July) 1951. 4. Ragan, G., Howes, E. L., Plotz, C. M., et al.: Effect of ACTH and cortisone on connective tissue. Bull. New York Acad. Med., 26 :25l (Apr.) 1950. 5. Plotz, C. M., Blunt, J. W., Ragan, C.: Effect of pituitary adrenocorticotropic hormone (ACTH) on disseminated lupus erythematosus. Arch. Dermat. & Syph., 61:913 (June) 1950. 6. Bourne, G. H.: Effect of cortisone and vitamin C on wound healing. Internat. Rev. Vitamin Re search, 24:318, 1952. 7. Palmerton, E. S.: The effect of local cortisone on wound healing in rabbit corneas. Am. J. Ophth., 40:344-53 (Sept.) 1955. 8. Bangham, A. D.: Effect of cortisone on wound healing. Brit. J. Exper. Path., 32:77 (Apr.) 1951. 9. Maumenee, A. E.: The influence of donor recipient sensitization on corneal grafts. Am. J. Ophth., 34:142 (May) 1951. 10. Ragan, C, Howes, E. L., Plotz, C. M., Meyer, K., and Blunt, J. W.: Effect of cortisone on granu lation tissue in rabbits. Proc. Soc. Exper. Biol. & Med., 72:718, 1949. 11. Howes, E. L., Plotz, C. M., Blunt, J. W., Ragan, C.: Retardation of wound healing by cortisone, Surgery, 28:177 (Aug.) 1950. 12. Findlay, C. W., and Howes, E. L.: The combined effect of cortisone and partial protein depletion on wound healing. New Eng. J. Med., 246 :597 (Apr.) 1952. 13. Greene, R. W., Faloon, W. W., and Lozner, E. L.: Use of ACTH in preparing patients with idiopathic thrombocytopenic purpura for splenectomy. Am. J. Med. Sc, 226:203 (Aug.) 1953. 14. Grant, G.: Effect of cortisone on healing of tendons in rabbits. J. Bone & Joint Surg., 35-A:525 (Apr.) 1953. 15. Gonzalez, R. I.: Effect of cortisone of healing of tendons in rabbits. J. Bone & Joint Surg., 35-A: 525 (Apr.) 1953. 16. Ashton, N.: Cortisone in ocular conditions. Lancet, 2:919 (Nov.) 1951. 17. Cole, J. W., Orbison, J. L. Holden, W. D., et al.: A histological study of the effect of cortisone on wound healing per primum. Surg Gynec. & Obst., 93:321 (Sept.) 1951. 18. Kay, J. A., Odell, R. T., and Taylor, L. W.: Failure of cortisone to delay or prevent the healing of fractures in rats. J. Bone & Joint Surg., 34-A :665 (July) 1952. 19. Daily, L., Jr., and Daily, R. K.: Present status of corneal transplantation. Texas State M. J., 49: 706 (Sept.) 1953. 20. McDonald, P. R., Leopold, I. H., Vogel, A. W., and Mulberger, R. D.: Hydrocortisone (Com pound F) in ophthalmology. Arch. Ophth, 49 :400 (Apr.) 1953.
T H E EFFECTS OF HYPOXIA AND
HYPEROXIA*
U P O N T H E OXYGEN T E N S I O N I N T H E VITREOUS H U M O R OF T H E CAT A R L I N G T O N C.
K R A U S E , M.D.,
AND S E Y M O U R B.
GOREN,
B.A.
Memphis, Tennessee INTRODUCTION
It is obvious that oxygen is necessary for the maintenance of retinal life. The mecha nisms by which oxygen is transported to and metabolized by the retina, however, are * From the Division of Ophthalmology, Depart ment of Surgery, of The University of Chicago. This investigation was supported by the Douglas Smith Foundation for Medical Research and the Chicago Community Trust of Chicago. Presented at the Midwest Section of the Association for Research in Ophthalmology, March 17, 1956, at Chicago.
not so well known. The diffusion of oxygen through the vitreous humor is one factor in
retinal metabolism. It has been found that, under normal conditions, the oxygen tension in the anterior chamber of the eye is 40 to 50 mm. Hg, while that in the posterior chamber is 100 to 120 mm. Hg. 1 The pur pose of the present study was to determine the relationships between the oxygen ten sion in the vitreous humor of the adult cat and the environmental conditions of hypoxia and hyperoxia.
759
16. Green, H., et. al.: Research Department, Wills Eye Hospital. Unpublished results. 17. Boudet, M., and Viallefont: Reported in Arch. Ophth., 54:793-794 (Nov.) 1955. 18. Ahmad, S. S.: Research Department, Wills Eye Hospital. Personal communication. 19. Wien, R., and Mason, D. F. J.: Pharmacology of M and B 2050. Lancet, March 7, 1953, pp. 454-455. 20. Waldman, S., and Pelner, L. Treatment of the ambulatory hypertensive patient with Pentolinium tartarate. Am. J. M. Sc, 231:140-150 (Feb.) 1956. 21. Clinical research report on Ansolysen. Wyeth Laboratories, Philadelphia.
E F F E C T O F STEROIDS ON T E N S I L E S T R E N G T H O F CORNEAL W O U N D S * A U S T I N I. F I N K ,
M.D.
Brooklyn, New York AND IRVING BARAS,
M.D.
New York INTRODUCTION
Cortisone has proven to be a useful ad junct in the treatment of certain inflamma tory eye diseases.1 However, this drug was initially not fully exploited in inflammatory processes following surgery because of early reports in the literature describing the inhibi tion of wound healing by cortisone.2"6 The majority of these reports were based on histologic studies,2-4-8 and conclusions as to tensile strength were merely inferred. In a recent article, Palmerton 7 reported that cortisone has an inhibitory effect on corneal wound healing. He made use of a technique whereby he measured directly the tensile strength of the wound. This technique was similar in many respects to one which we employed in measuring the effect of corti sone on corneal wound healing. The study which was carried out in 1952-53 and pre sented to the Eastern Section of the Associa tion for Research in Ophthalmology in February, 1954, demonstrated no such in hibitory effect by cortisone. The difference ♦From the Department of Surgery (Ophthal mology) of the Cornell University Medical College. Presented before the Eastern Section of the As sociation for Research in Ophthalmology, February, 1954, Philadelphia, Pennsylvania.
in conclusions might be attributed to certain fundamental variances in technique: a. No mention was made by Palmerton of the use of anticoagulants for the preven tion of clotting of the rabbit aqueous by the fibrinogen contained therein. A fibrin would have a tendency to become interposed be tween the lips of the wound and thus prevent consistent cornea-to-cornea wound approxi mation. More pronounced variability could thus be expected. b. The length of the corneal wound em ployed by Palmerton was five mm. We had tried a wound of this size and discarded it as unsatisfactory. It was our experience that a seven-mm. corneal incision afforded us a more accurate bursting point. c. Our traction sutures were placed at the time of surgery, while Palmerton placed his at the time of testing. We felt that trauma to the cornea and distortion of the wound edges would occur if traction sutures were placed just prior to measuring the bursting point of the wound. One cannot adequately estimate to what extent this added manipulation has impaired the solidity and therefore the ten sile strength of the wound. Another factor of variability has thus been introduced. d. We would like to point out that there
760
AUSTIN I. FINK AND IRVING BARAS
was a considerable difference in the method of administration of the cortisone. Palmerton mentions the use of both topical and subconjunctival cortisone, whereas we em ployed the intramuscular route. We make no attempt to correlate differences as a result of this particular variation but wish to men tion that it existed. We feel that these differences have enabled us to obtain a more accurate evaluation of the tensile strength of the wound. Our ad ditional clinical experience in recent years with cortisone in patients following cataract extraction and corneal grafting supports the conclusions drawn in our paper. We there fore feel that reporting of our thus far un published work may be of value in shedding further light on this controversial question. METHOD TECHNIQUE
A corneal incision of specified length was made. The wound edges were then pulled apart after a certain number of days. The quantity of force found necessary to ac complish this disruption was then used as a measure of the tensile strength of the wound. A seven-mm. linear scratch was made in the center of the cornea to outline the posi tion of the corneal incision. Two intracorneal sutures were then placed four mm. on either side of the scratch. They ran through the cornea for a distance of approximately five mm. and were tied with a short loop. These loops were to be used later as points of fixation for disrupting the corneal wound. A Stallard-type suture, three mm. in length, was placed so as to straddle the cen ter of the corneal scratch. The loop of this center suture was then pulled aside, and a seven-mm. incision was made with a Wheeler knife at the site of the previous corneal scratch (fig. 1). The anterior chamber was then irrigated with 2.5-percent sodium citrate in order to prevent clotting action by the fibrinogen contained in the rabbit aqueous. If this were not done, a fibrin clot might become inter-
Figs. 1 and 2 (Fink and Baras). The surgical technique. posed between the lips of the wound and thus prevent adequate approximation. The Stallard-type suture was then pulled taut and tied to re-approximate the wound edges (fig. 2). Atropine sulfate (50 percent) was then instilled in the eye followed by penicillin ointment (500 [Ag.). The lids were then sutured together. After a specified period of time, varying from three days to a week, the wounds were disrupted. This was accomplished by at taching a tiny hook to each of the preplaced intracorneal loop sutures. The Stallard suture was then cut. The hooks were then attached to strings which ran over pulleys and were in turn connected to a weighting pan. BB shot was then slowly added to the weighing pan until the wound edges separated and aqueous was lost (fig. 3). The pan and BB shot were then weighed arid this figure was recorded as a measure of the tensile strength of the wound. The rabbits were divided into two groups. One group received daily subcutaneous in jections of cortisone (15 mg./kg. of body
761
E F F E C T O F STEROIDS ON CORNEAL W O U N D S
Fig. 3 (Fink and B a r a s ) . Tech nique of wound disruption.
weight). This dosage had been used pre viously by Maumenee9 in investigating the role of cortisone in corneal graft sensitization. Cortisone was administered immediately following surgery and continued until the wound was disrupted. The second group re ceived nothing. OBSERVATIONS
Included in this study are observations made on 71 rabbit eyes. Many more eyes had been operated upon but could not be used for the following reasons: a. Intraocular infections. This complica tion was found more often in rabbits receiv ing cortisone and occurred in approximately one out of four rabbits. b. Sloughing of sutures. It was, as pre viously mentioned, necessary to place all sutures intracorneally, in order to preserve the anterior chamber and prevent premature clotting of the aqueous. The rabbit cornea is
extremely thin. This made it difficult to place the sutures intracorneally and at the same time deep enough to prevent sloughing. c. Poor approximation of the wound edges. The eyes were inspected grossly and all those with poorly approximated wound edges were discarded. The principal observation of this study was that cortisone had no significant influ ence on the tensile strength of corneal wounds in rabbits. The animals were divided into three separate groups; those with wounds which were disrupted on the fourth, the fifth, and the seventh day following sur gery. It is noted that the tensile strength of the wounds gradually increased from the fourth to the seventh day (table 1). In the first series of experiments, as dem onstrated by Table 4, the average tensile strength of the wounds in the cortisone treated rabbits exceeded that of the un treated animals. However, the technique of
TABLE 1 CORTISONE AND CORNEAL WOUND HEALING: SUMMARY OF FIRST EXPERIMENT
A Number of Eves Average Tensile Strength Standard Deviation "t" Conclusion
Four Days B
10 77 gm. 22
10 93 gm. 11
1.49 Not significant
K E Y : A: Control rabbits; B : cortisone-treated rabbits.
A
Five Days
18 98 gm. 25
Seven Days
B
A
8 105 gm. 19
10 121 gm. 29
0.64 Not significant
B
4 160 gm. 13
2.49 Nearly significant
762
AUSTIN I. FINK AND IRVING BARAS
T E N S I L E S T R E N G T H
I N
So
G R A M S
A
.5
3>"YS
*
5
&
^7
Akr
Graph 1 (Fink and Baras). Observations in studies on cortisone and corneal wound healing.
the experiment gave rise to a considerable experimental variation as evidenced by the large standard deviation. The figures were then submitted to further statistical analysis in order to determine whether the difference between the two groups was actually significant or lay within the limits of experimental error. The "t" test was used as the criterion (the letter "t" represents the ratio between the difference of the treated and untreated groups and the standard error of the difference). The four- and five-day series were then found to be not significant. The seven-day group was found to approach statistical significance. A second series of seven-day studies was therefore undertaken. The rea sons for further study were twofold: (a)
The cortisone-treated group in the first series was small; (b) we wished to introduce further statistical controls. This included pairing of the treated and untreated animals, with recording of weight and sex. The results in this series were then analyzed, utilizing the "t" test and the differ ence between the treated and untreated group was found not significant (table 2). DISCUSSION
The observations of this study have led us to assume that the use of cortisone does not materially affect the tensile strength of corneal wounds in rabbits. This statement would seem to be in direct variance with many previously published reports dealing with cortisone and wound healing. Ragan10
EFFECT OF STEROIDS ON CORNEAL WOUNDS TABLE 2 CORTISONE AND CORNEAL WOUND HEALING: SUMMARY OF SECOND EXPERIMENT
Number of Animals Average Tensile Strength Standard Deviation " t " test Conclusion
Control Rabbits
CortisoneTreated Rabbits
6 137 gm. 26
6 141 gm. 31
0.38 Not significant
was first to demonstrate the inhibition of wound healing by cortisone. Many papers, dealing with this subject, have been pub lished since that time. Most have agreed with Ragan's conclusion 5,6 ' 11 while others have found the steroids to be without effect in wound healing.12-15 Investigations on animals have fallen into two groups; histologic studies and experi ments in which the criterion was the me chanical bursting strength of the wound. The majority of investigators seem to agree that there is a general supression of fibroblastic proliferation in cortisone-treated animals. There have been a number of other studies in which the steroids exhibited little or no effect on wound healing. Bangham8 found that cortisone had no effect on guinea pigs but did cause retarda tion in rabbits. He attributed this to a species difference. This might also account for the lack of response, reported by Ragan 10 in cortisone-treated rats. Findlay and Homes 12 found cortisone to have no effect on wound healing in rabbits placed on a normal diet. Those with protein depletion, due to weight loss, showed retardation in healing when placed on cortisone. Ashton16 found no inhibition with this steroid when therapeutic doses were given. In larger doses there was a delay in healing. Cole and Orbison,17 experimenting with dogs, found that sutured wounds healing per primam were not affected by cortisone. They
763
point out that wound healing per primam re quires less capillary proliferation and fibro blastic response than those healing by second ary intention. Grant14 and Gonzalez15 work ing on experimental tendon repair in rabbits found no inhibition with cortisone. There has accumulated a small number of reports showing cortisone to have no effect on wound healing in man. Greene and coworkers 13 reported normal healing in corti sone-treated patients upon whom splenectomies were performed. Kay and Odell18 cite three cortisone-treated arthritics upon whom reconstructive foot operations were performed without any impairment of heal ing. Daily and Daily19 feel that the topical use of cortisone in corneal transplantation, both at the time of surgery and postoperatively, reduces the hazard of operation. Certain of the above studies deserve added comment in relation to our own observations and technique. It was our purpose to have these wounds heal by primary intention thus paralleling Cole's observations on dogs. Maintaining our rabbits on a normal diet without protein loss might have prevented a deleterious influence by cortisone. It is not the purpose of this paper to dis pute the well-substantiated histologic evi dence demonstrating the inhibition of fibro blastic proliferation in the cornea with the use of cortisone.2-16'20 However, from a re view of our observations, it would not be unreasonable to assume that there is little or no relationship between the histologic picture in a corneal wound and the actual tensile strength of that wound. CONCLUSION
Under the conditions of this experiment and in the animals tested it is our belief that cortisone seems to exert no significant effect on the tensile strength of experimentally induced corneal wounds in rabbits. 451 Clarkson Avenue (3).
REFERENCES 1. Gordon, D. M., McLean, J. M., et al.: The use of A C T H and cortisone in oohthalmoloev Am T Ophth., 34:1675-1686 (Dec.) 1951.
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AUSTIN I. FINK AND IRVING BARAS
2. Ashton, N., and Cook, C.: Effect of cortisone on healing of corneal wounds. Brit. J. Ophth., 35 :708 (Nov.) 1951. 3. Newell, F. W., and Dixon, J. M.: Effect of subconjunctival cortisone upon the immediate union of experimental corneal grafts. Am. J. Ophth., 34:977 (July) 1951. 4. Ragan, G., Howes, E. L., Plotz, C. M., et al.: Effect of ACTH and cortisone on connective tissue. Bull. New York Acad. Med., 26 :25l (Apr.) 1950. 5. Plotz, C. M., Blunt, J. W., Ragan, C.: Effect of pituitary adrenocorticotropic hormone (ACTH) on disseminated lupus erythematosus. Arch. Dermat. & Syph., 61:913 (June) 1950. 6. Bourne, G. H.: Effect of cortisone and vitamin C on wound healing. Internat. Rev. Vitamin Re search, 24:318, 1952. 7. Palmerton, E. S.: The effect of local cortisone on wound healing in rabbit corneas. Am. J. Ophth., 40:344-53 (Sept.) 1955. 8. Bangham, A. D.: Effect of cortisone on wound healing. Brit. J. Exper. Path., 32:77 (Apr.) 1951. 9. Maumenee, A. E.: The influence of donor recipient sensitization on corneal grafts. Am. J. Ophth., 34:142 (May) 1951. 10. Ragan, C, Howes, E. L., Plotz, C. M., Meyer, K., and Blunt, J. W.: Effect of cortisone on granu lation tissue in rabbits. Proc. Soc. Exper. Biol. & Med., 72:718, 1949. 11. Howes, E. L., Plotz, C. M., Blunt, J. W., Ragan, C.: Retardation of wound healing by cortisone, Surgery, 28:177 (Aug.) 1950. 12. Findlay, C. W., and Howes, E. L.: The combined effect of cortisone and partial protein depletion on wound healing. New Eng. J. Med., 246 :597 (Apr.) 1952. 13. Greene, R. W., Faloon, W. W., and Lozner, E. L.: Use of ACTH in preparing patients with idiopathic thrombocytopenic purpura for splenectomy. Am. J. Med. Sc, 226:203 (Aug.) 1953. 14. Grant, G.: Effect of cortisone on healing of tendons in rabbits. J. Bone & Joint Surg., 35-A:525 (Apr.) 1953. 15. Gonzalez, R. I.: Effect of cortisone of healing of tendons in rabbits. J. Bone & Joint Surg., 35-A: 525 (Apr.) 1953. 16. Ashton, N.: Cortisone in ocular conditions. Lancet, 2:919 (Nov.) 1951. 17. Cole, J. W., Orbison, J. L. Holden, W. D., et al.: A histological study of the effect of cortisone on wound healing per primum. Surg Gynec. & Obst., 93:321 (Sept.) 1951. 18. Kay, J. A., Odell, R. T., and Taylor, L. W.: Failure of cortisone to delay or prevent the healing of fractures in rats. J. Bone & Joint Surg., 34-A :665 (July) 1952. 19. Daily, L., Jr., and Daily, R. K.: Present status of corneal transplantation. Texas State M. J., 49: 706 (Sept.) 1953. 20. McDonald, P. R., Leopold, I. H., Vogel, A. W., and Mulberger, R. D.: Hydrocortisone (Com pound F) in ophthalmology. Arch. Ophth, 49 :400 (Apr.) 1953.
T H E EFFECTS OF HYPOXIA AND
HYPEROXIA*
U P O N T H E OXYGEN T E N S I O N I N T H E VITREOUS H U M O R OF T H E CAT A R L I N G T O N C.
K R A U S E , M.D.,
AND S E Y M O U R B.
GOREN,
B.A.
Memphis, Tennessee INTRODUCTION
It is obvious that oxygen is necessary for the maintenance of retinal life. The mecha nisms by which oxygen is transported to and metabolized by the retina, however, are * From the Division of Ophthalmology, Depart ment of Surgery, of The University of Chicago. This investigation was supported by the Douglas Smith Foundation for Medical Research and the Chicago Community Trust of Chicago. Presented at the Midwest Section of the Association for Research in Ophthalmology, March 17, 1956, at Chicago.
not so well known. The diffusion of oxygen through the vitreous humor is one factor in
retinal metabolism. It has been found that, under normal conditions, the oxygen tension in the anterior chamber of the eye is 40 to 50 mm. Hg, while that in the posterior chamber is 100 to 120 mm. Hg. 1 The pur pose of the present study was to determine the relationships between the oxygen ten sion in the vitreous humor of the adult cat and the environmental conditions of hypoxia and hyperoxia.