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The Corneal Graft: A Multiple Variable Analysis of the Penetrating Keratoplasty
AMERICAN JOURNAL VOLUME
72
OF OPHTHALMOLOGY
JULY, 1971
NUMBER 1, PART 2
THE CORNEAL GRAFT: A MULTIPLE VARIABLE ANALYSIS OF THE PENETRATING KERATOPLASTY THOMAS E.
M O O R E , J R . , M.D.,
AND S A M U E L B. ARONSON,
M.D.
San Francisco, California
The period of delayed graft reaction be gins when the early graft reaction ends and extends indefinitely. Variables in this period include: (1) microbiology of the external eye, (2) immunologic factors in the host re sponse, (3) pre- and postoperative morphol ogy of the host eye, and (4) socioeconomic status of the recipient. Morphologic struc ture and socioeconomic status proved to be the critical variables in delayed graft failure. The combination of early and delayed graft results makes up the long-term graft results for this series. Patients have been followed for a maximum of five years, so that definite long-term prognoses cannot be presented. However, the incidence of delayed graft reac tion appears to diminish with time, so that reasonable projections can be made. To evaluate clinical variables more exten sively simultaneous studies were done in the rabbit. The early graft period was desig nated arbitrarily at 75 days, although sutures were removed between 10 and 14 days. Such early suture removal was required if a suc cessful graft was to be achieved. The vari ables studied in this period were: (1) the surgical procedure, (2) suture toxicity, (3) pathogenic and indigenous bacterial toxicity, (4) tissue noncompatibility, and (5) genetic variability of the host. The factors of princi pal significance were: (1) the surgical pro cedure, (2) the suture material, and (3) ge netic composition. The delayed graft reaction was evaluated in rabbits 90 days following surgery. De Reprint requests to Thomas E. Moore, Jr., M.D., Suite 309, 45 Castro Street, San Francisco, Califor layed reactions were studied under both nia 94114. spontaneous and experimental conditions.
Since the early period of keratoplasty, ophthalmic surgeons have anticipated a good outcome in the grafting of any diseased cor nea. In the past, success could be attained only in patients with good prognosis. To maximize the possibility of success, we at tempted to identify and define accurately the operative variables associated with graft fail ure. Early in this attempt, it became evident that variables could be subdivided into two general groups according to time of occur rence : (1) the period of early graft reaction, and (2) the delayed reaction period. The early period (Fig. 1) extended from the time of surgery until suture removal. Arbitrarily se lected variables in this period were: (1) se lection of the donor graft tissue, (2) thera peutic protocols before and after surgery, (3) adjunctive medical therapy in the post operative period, and (4) standardization of surgical technique to permit classification of each procedure. Variables evaluated and compared include: (1) morphologic status of the host eye, (2) etiologic and syndromal di agnosis of the host eye, (3) surgical proce dures, (4) suture materials and techniques, (5) microbially-induced reactions, (6) immunologic status of the host, and (7) tissue noncompatibility. The variables found to be essential in the early graft period were: (1) morphologic classification, (2) surgical pro cedure, and (3) suture material.
205
AMERICAN JOURNAL OF OPHTHALMOLOGY
206
JULY, 1971
A. latency before inflam motion B. early graft reaction C. inflammatory resolution D. delayed graft reaction X physiologic failure
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Fig. 1 (Moore and Aronson). The corneal graft reaction. The early graft reaction comprises periods B and C in a successful graft and B and X in graft failure. The delayed graft reaction comprises D in a successful graft and X in graft failure.
Variables evaluated include: (1) bacterial and antigenic stimuli, (2) immune compe tence of the host response, and (3) the se verity of structural alteration. The rabbit graft experiments strongly support the ob servations made in the human series and provide a much more accurate appraisal of several factors in graft failure, e.g., the role of the tissue noncompatibility reaction. How ever, these observations cannot be used to verify aspects of the human data, but only to support it. Finally, a large number of variables have been analyzed by discriminant function. This procedure provides statistical evidence to sup
port some of our observations, e.g., the surgi cal procedure and suture toxicity. Similarly, it demonstrates that others are not statisti cally valid, e.g., immunologic evaluation. The strength of this technique is that an indepen dent evaluation has utilized prospective data from our graft series and has placed in perspective the importance of each studied variable. Although these studies have fallen some what short of our projected goal—namely, to graft successfully any vision-reducing cornea —they present an integrated approach to the corneal graft whereby that goal can one day be reached.
72
OF OPHTHALMOLOGY
JULY, 1971
NUMBER 1, PART 2
THE CORNEAL GRAFT: A MULTIPLE VARIABLE ANALYSIS OF THE PENETRATING KERATOPLASTY THOMAS E.
M O O R E , J R . , M.D.,
AND S A M U E L B. ARONSON,
M.D.
San Francisco, California
The period of delayed graft reaction be gins when the early graft reaction ends and extends indefinitely. Variables in this period include: (1) microbiology of the external eye, (2) immunologic factors in the host re sponse, (3) pre- and postoperative morphol ogy of the host eye, and (4) socioeconomic status of the recipient. Morphologic struc ture and socioeconomic status proved to be the critical variables in delayed graft failure. The combination of early and delayed graft results makes up the long-term graft results for this series. Patients have been followed for a maximum of five years, so that definite long-term prognoses cannot be presented. However, the incidence of delayed graft reac tion appears to diminish with time, so that reasonable projections can be made. To evaluate clinical variables more exten sively simultaneous studies were done in the rabbit. The early graft period was desig nated arbitrarily at 75 days, although sutures were removed between 10 and 14 days. Such early suture removal was required if a suc cessful graft was to be achieved. The vari ables studied in this period were: (1) the surgical procedure, (2) suture toxicity, (3) pathogenic and indigenous bacterial toxicity, (4) tissue noncompatibility, and (5) genetic variability of the host. The factors of princi pal significance were: (1) the surgical pro cedure, (2) the suture material, and (3) ge netic composition. The delayed graft reaction was evaluated in rabbits 90 days following surgery. De Reprint requests to Thomas E. Moore, Jr., M.D., Suite 309, 45 Castro Street, San Francisco, Califor layed reactions were studied under both nia 94114. spontaneous and experimental conditions.
Since the early period of keratoplasty, ophthalmic surgeons have anticipated a good outcome in the grafting of any diseased cor nea. In the past, success could be attained only in patients with good prognosis. To maximize the possibility of success, we at tempted to identify and define accurately the operative variables associated with graft fail ure. Early in this attempt, it became evident that variables could be subdivided into two general groups according to time of occur rence : (1) the period of early graft reaction, and (2) the delayed reaction period. The early period (Fig. 1) extended from the time of surgery until suture removal. Arbitrarily se lected variables in this period were: (1) se lection of the donor graft tissue, (2) thera peutic protocols before and after surgery, (3) adjunctive medical therapy in the post operative period, and (4) standardization of surgical technique to permit classification of each procedure. Variables evaluated and compared include: (1) morphologic status of the host eye, (2) etiologic and syndromal di agnosis of the host eye, (3) surgical proce dures, (4) suture materials and techniques, (5) microbially-induced reactions, (6) immunologic status of the host, and (7) tissue noncompatibility. The variables found to be essential in the early graft period were: (1) morphologic classification, (2) surgical pro cedure, and (3) suture material.
205
AMERICAN JOURNAL OF OPHTHALMOLOGY
206
JULY, 1971
A. latency before inflam motion B. early graft reaction C. inflammatory resolution D. delayed graft reaction X physiologic failure
>-
y
ui
>
V)
/
/
y y
S
£ ~" -^
\
\
/ / /
« A:—*
/
/
/
/
X
^
B.
C.
/ \
\
\
\
\
\
/
,C
y '
s
r> X . yl
\
A
\ \
TIME
Fig. 1 (Moore and Aronson). The corneal graft reaction. The early graft reaction comprises periods B and C in a successful graft and B and X in graft failure. The delayed graft reaction comprises D in a successful graft and X in graft failure.
Variables evaluated include: (1) bacterial and antigenic stimuli, (2) immune compe tence of the host response, and (3) the se verity of structural alteration. The rabbit graft experiments strongly support the ob servations made in the human series and provide a much more accurate appraisal of several factors in graft failure, e.g., the role of the tissue noncompatibility reaction. How ever, these observations cannot be used to verify aspects of the human data, but only to support it. Finally, a large number of variables have been analyzed by discriminant function. This procedure provides statistical evidence to sup
port some of our observations, e.g., the surgi cal procedure and suture toxicity. Similarly, it demonstrates that others are not statisti cally valid, e.g., immunologic evaluation. The strength of this technique is that an indepen dent evaluation has utilized prospective data from our graft series and has placed in perspective the importance of each studied variable. Although these studies have fallen some what short of our projected goal—namely, to graft successfully any vision-reducing cornea —they present an integrated approach to the corneal graft whereby that goal can one day be reached.