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Plasma Implantations in the Cornea*
PLASMA IMPLANTATIONS IN T H E CORNEA
tors which maintain the tension within the eye at a normal value," finds suggestive corroboration in the results obtained in the descendants of glaucomatous animals. The mechanism concerned in hereditary transmission of glaucoma is unknown. Most observers accept the concept that- in con genital glaucoma the structure of the eye varies from normal. Malformations of the filtration angle, small eyes, and large lenses
701
have been implicated. These investigations indicate that an instability of intraocular pressure exists in animals without any of these stigmas. This instability is produced by abnormalities of secretion of pituitary principles and by impaired diencephalic cen ters concerned with the regulation of intra ocular pressure. 2805 Oatis Avenue (6).
REFERENCES
1. Parsons, J. H.: Pathology of the Eye. London, Putnam, 3 :1111. 1908. 2. Reis, W.: Arch. f. Ophth, 60:1, 1905. 3. Meisner: Arch. f. Ophth., 112:433, 1923. 4. Byers, W. G. M.: Arch. Ophth., 6 :S78, 1931. 5. Barkan, O.: Arch. Ophth., 43 :793, 1950. 6. Callahan, A.: J. M. A. Alabama, 19:13, 1949. 7. Weekers, L., and Weekers, R.: Ann. ocul., 182 :869, 1949. 8. Schmerl, E., and Steinberg, B.: Am. J. Ophth., 31:1097, 1948. 9. : Am. J. Ophth., 35 :469 (Apr.) 1952. 10. : Am. J. Ophth., 32 :947, 1950. 11. Berens, C.: The Eye and Its Diseases. Philadelphia, Saunders, 1936, p. 463. 12. Elwyn, H.: Am. J. Ophth., 33 :1373,1950.
PLASMA IMPLANTATIONS IN T H E CORNEA* G. W.
H.
M.
VAN A L P H E N ,
M.D.
Leyden, Holland
Up to the present time the problems of the fate of the corneal transplant, the con servation of its individuality or its partial and/or total absorption and substitution, have been studied by means of microscopic follow-ups of transplants. These investigations were seriously handi capped by the fact that a great similarity existed in the microscopic picture between the host cornea and the graft. Furthermore, it is not known in which manner a total sub stitution occurs, if indeed it occurs at all. In vestigations with artificially induced scars do * From the University Eye Clinic. I wish to thank Dr. P. van der Meer, Dr. J. A. Cohen, Dr. H. L. Booy, Prof. P. J. Gaillard, Dr. G. J. Verdonck, and Mr. W. A. Blokhuis for their unstinted help and valuable discussions, and Mr. L. Beumer for his help in laboratory technique.
not sufficiently indicate the full regenerative potency of the cornea. These difficulties are overcome on implant ing a graft without a histologic structure, having the property of gradual absorption. In these circumstances it becomes possible to study the "pure" behavior of the host cornea, itself. Blood plasma was chosen as the "graft." It has no histologic structure and, if placed in the anterior chamber of the eye, was shown to dissolve in about a fortnight. Biochemi cally, however, plasma shows a definite struc ture; this is of possible value in the results of the implantation. The incorporation into tissue cultures of certain structures, such as threads of nylon or glass, and the influence of the highest tension in the underlying rubber-base much
702
G. W. H. M. VAN ALPHEN
Fig. 1 (van Alphen). Host cornea (to the left) and plasma graft four days after implantation. The graft is partially torn off. The proliferation of the host cornea's endothelium is continued over onto the graft (E-E). The epithelium has also proliferated, though rather less than the photograph would seem to indi cate. In the graft, remains of the plasma are still clearly visible, particularly in the form of bars. Note the migrated cells. improve the rate of cell migration ( W e i s s * ) . Since plasma has a fibrillar structure, a stimulating influence on cell migration may be expected.
first implantation was carried out following Castroviejo's method.1" From this experiment it became clear that the operation itself was feasible; since the anterior chamber was reformed and the graft did not dissolve too rapidly, the eye was preserved. Because the fixation sutures cut deeply into the soft plasma, however, all the next implantations were fixed by means of contact glasses. Six plastic contact glasses of different sizes were manufactured to fit rabbits' eyes. Prior to each operation the best-fitting glass was selected. The normal cornea was then trephined under atropine, and the plasma film was cut with the same trephine. The excised piece of plasma film was then inserted into the eye, a contact glass was placed upon it, and firm pressure was applied for one to two minutes. The plasma soon adhered to the borders of the cornea and, at the end of this time in most cases, the anterior chamber had reformed. Penicillin-atropine ointment was applied and the eyelid sutured.
PREPARATION OF PLASMA
Rabbit blood, obtained on puncture of the heart, is received into a tube over oxalate of sodium and centrifuged. The oxalated plasma is sucked up and precipitated at 37° C. with a quantity of CaCl 2 , such that the clotting-time passes a minimum. As this plasma contains calcium, another method was employed later on in which blood was centrifuged in ice-cooled paraffined tubes. Then the syneresis water is removed from the plasma clot by applying slight pressure. A good plasma film, nearly two mm. in thickness, is obtained in this way. IMPLANTATION
The cornea of a rabbit was totally tre phined (diameter 4.1 mm.) and a plasma film of the same diameter was inserted. The ♦Weiss, P . : Arch. f. Entw. Mechan., 116:438, 1929.
Fig. 2 (van Alphen). High-power view of Figure 1. Proliferation of endothelium at the edge of the host cornea's Descemet's membrane. 11 wish to thank Dr. C. Kok van Alphen for carrying out this first implantation, Dr. E. G. Wijngaarde for valuable assistance in the other experiments, and Mr. D. Laman for anesthesia.
PLASMA IMPLANTATIONS IN THE CORNEA
703
S U B S E Q U E N T COURSE
At the end of three days, in most cases, no details were visible, as the dissolving plasma clouds the contact glass. After six to eight days, the contact glass is removed and the graft shows a chalk-white colora tion. After 10 days the color of the graft has, more or less, the aspect of milky glass. O n the 12th to 16th day, small radial blood vessels appear, originating in the limbus in the direction of the graft and pene trating into the graft in only a few of the observed cases. These vessels disappear again in from four to eight days. Twelve to 24 days after operation, the borders of the graft start to become transparent, and this pro ceeds extremely slowly toward the center of the graft. In all, 32 rabbits were operated T h e results w e r e :
upon.
Lost (panophthalmia) 4 Enucleation within 25 days of implantation 6 Thick macula corneas 10 Thin macula corneas 12 The transparency may be tabulated as fol lows : Cleared up at the borders 10 Clear epithelium and but slight stroma cloudiness and cloudy Descemet's mem brane 5 Clear epithelium and stroma; Descemet's membrane still cloudy 2 The same but with a very slight central clouding of Descement's membrane .. 2 Absolutely transparent 0 In only five cases was the implanted plasma film obtained from the blood of the same rabbit on which it was later grafted. I n all other cases, the plasma was derived from an arbitrarily chosen rabbit. In the
Fig. 4 (van Alphen). Later phase of proliferation of the endothelium at the edge of the host's Descemet's membrane. Beginning of new Descemet formation (three to four weeks after implantation).
P il *<*
Fig. 3 (van Alphen). Enlarged part of the plasma graft of Figure 1. Migration of endothelial cells. results, however, no difference was notice able ; a retarded dissolving of the plasma of auto-implants in the anterior chamber was suggested by the longer duration of cloudi ness of the aqueous. T h e microscopic sections of the 28 im plantations show the manner in which the plasma is being "rebuilt" into normal cor nea. T h i s process and its variations will be summarized here.
704
G. W. H. M. VAN ALPHEN scopic sections of the plasma-implanted cor neas still clearly show the original prolifera tion of the endotheHum at the edges of the host's Descemet's membrane. The host cornea's epithelium also is pro liferating—though much less intensively than the endotheHum—and these epithelial Cells, four days after implantation, have already crossed over to the edges of the plasma graft. Numbers of these cells appear to come loose from the context of the epi thelium, and to swarm into the plasma in a similar manner. LATER COURSE
Fig. 5 (van Alphen). Beginning of new Descemet formation (three to four weeks after implan tation). The graft, four days after the implanta tion, is wholly filled with spindle-shaped cells, many of which show mitotic division. The indication of the origin of these cells is very clear indeed—endotheHum of the host cornea at the edge of Descemet's membrane has pro liferated enormously and these endotheHum cells are migrating into the plasma graft. These migrated cells completely correspond in shape, size, and structure to the cells of the original endotheHum. Nearly all micro-
Fig. 6 (van Alphen). Proliferation of the endothelium eight weeks after implantation. Note host's Descemet's membrane and newly formed Descemet's of the graft.
In the protoplasm of the spindle-shaped cells in the graft, after eight to 15 days, a distinct fibrillary structure appears, which is shown exclusively, at the beginning, in the Gomorry-stained specimens; and later also with the Weigert-Gieson staining method. In the same period many specimens also show the beginnings of lamellar forma tion and flattening of the cells. In a later phase—about eight weeks after implantation—the newly formed stroma is hardly to be distinguished from the stroma of the host cornea in many cases. The lamel lar structure, in about half the cases, shows slight to very distinct irregularities, due largely to inflammation which may be ac companied by ingrowing blood vessels. In the initial phases of the chronic proliferative inflammation, a strong mesenchymal proliferation occurs, which shows exudate, leukocytes, accumulation of histiocytes, mast cells, and phagocytic giant cells. In later phases all this results in a very irregularly built fibrous tissue. In the early phases the stroma of the host cornea is, in many cases, slightly infiltrated with leukocytes. The stroma cells situated in the near vicinity of the graft are con siderably swollen, but no signs of mitosis were ever observed. In half the number of cases, a newly formed intact endotheHum was found and, moreover, a newly formed Descemet's mem-
PLASMA IMPLANTATIONS IN THE CORNEA brane was present in six of the cases. This new Descemet's membrane is thinner and stains more faintly than the host Descemet's membrane. Apart from these findings in three of the seven eyes enucleated early in the experiment (three to four weeks after implantation), Descemet's membrane was present in a rudimentary form. In only four cases was the epithelium absent. All the other cases showed intact epitheliums, some of which were very reg ular, and others considerably irregular in appearance. In two cases, large bullae had formed. In one case, there was such a pro liferation of the epithelium that it resembled a granuloma.* Even three to four weeks after implanta tion, definite parts of the epithelium clearly indicated a gradual transition of epithelium cells into stroma cells. It is obvious that the epithelium takes its part in the building-up of the stroma, though to a much lesser ex tent than the endothelium. The time of epithelization of the surface of the graft varies considerably—between 12 and 30 days—being determined by means of fluorescein staining in the living eye. In one of the microscopic sections a very regular intact epithelium was found as early as 14 days after implantation. Bowman's membrane is absent in rabbits and it may be that its function is taken over by the basal membrane of the epithelium. In 10 cases the new epithelium showed a dis tinct basal membrane. A summary of microscopic findings in 22 eyes enucleated after more than three weeks following implantation shows:
70S
I .. 7 'van Alphen). The newly formed stroma, _'0 dajs after implantation. Migrating endothelial cells constitute a three-dimensional reticulum. STROMA
Regular Irregular Fibrous Vascularization
10 12 S S
DESCEMET'S MEMBRANE
Present Indicated
6 3
ENDOTHELIUM INTACT
11
SYNECHIAS (anterior)
7
EPITHELIUM
Absent Present Regular Irregular BASAL MEMBRANE
4 18 11 7 10
* In this case, in the newly formed stroma many cells resembling eosinophilic leukocytes were found, the significance of whicli remains obscure.
Fig. 8 (van Alphen). Gradual transition of epi thelial cells of the graft into stroma cells (three to four weeks after implantation).
706
G. W. H. M. VAN ALPHEN
4uW
CONCLUSIONS
F r o m experimental work on rabbits it be came clear that implantation of a plasma film into a wholly trephined normal cornea is possible; fixation being by means of a contact glass. It was shown that the host cornea is able to build up into this plasma medium a new tissue which very closely resembles the nor mal cornea in histologic structure and trans parency (a slight central clouding of Desce met's membrane excepted). The host cornea's endothelium appears to be essentially significant in the formation of
OPHTHALMIC
Fig. 9 (van Alphen). Host cor nea and newly formed cornea three months after implantation. The place of transition is marked by a slight irregularity in the lamellar structure of the stroma. Also the host's Descemet's membrane is thicker and stains more deeply than the newly formed Descemet. Re mains of proliferation of the endothelium.
stroma, Descemet's membrane, and the new endothelium. T h e new epithelium is derived from the host cornea's epithelium, the proliferation of which may also be of some significance in the stroma formation, though its share seems to be rather slight. These investigations appear to be of theoretical value only, in so far as they in dicate the potency of the host cornea, the possibility of corneal regeneration in a proper medium, and the manner in which this re generation takes place. University
Eye
Clinic.
MINIATURE
W h e n the adhesion (symblepharon) begins at, is continuous with, and arises from that part of the conjunctiva which is reflected from the lid to the ball of the eye, so that on raising the eyelid a broad attachment is perceived, restraining the motions of the eye, it ought not to be meddled with for it may be increased, but it will never be diminished. Guthrie, Lecture on the Operative Surgery of the Eye, 1830.
tors which maintain the tension within the eye at a normal value," finds suggestive corroboration in the results obtained in the descendants of glaucomatous animals. The mechanism concerned in hereditary transmission of glaucoma is unknown. Most observers accept the concept that- in con genital glaucoma the structure of the eye varies from normal. Malformations of the filtration angle, small eyes, and large lenses
701
have been implicated. These investigations indicate that an instability of intraocular pressure exists in animals without any of these stigmas. This instability is produced by abnormalities of secretion of pituitary principles and by impaired diencephalic cen ters concerned with the regulation of intra ocular pressure. 2805 Oatis Avenue (6).
REFERENCES
1. Parsons, J. H.: Pathology of the Eye. London, Putnam, 3 :1111. 1908. 2. Reis, W.: Arch. f. Ophth, 60:1, 1905. 3. Meisner: Arch. f. Ophth., 112:433, 1923. 4. Byers, W. G. M.: Arch. Ophth., 6 :S78, 1931. 5. Barkan, O.: Arch. Ophth., 43 :793, 1950. 6. Callahan, A.: J. M. A. Alabama, 19:13, 1949. 7. Weekers, L., and Weekers, R.: Ann. ocul., 182 :869, 1949. 8. Schmerl, E., and Steinberg, B.: Am. J. Ophth., 31:1097, 1948. 9. : Am. J. Ophth., 35 :469 (Apr.) 1952. 10. : Am. J. Ophth., 32 :947, 1950. 11. Berens, C.: The Eye and Its Diseases. Philadelphia, Saunders, 1936, p. 463. 12. Elwyn, H.: Am. J. Ophth., 33 :1373,1950.
PLASMA IMPLANTATIONS IN T H E CORNEA* G. W.
H.
M.
VAN A L P H E N ,
M.D.
Leyden, Holland
Up to the present time the problems of the fate of the corneal transplant, the con servation of its individuality or its partial and/or total absorption and substitution, have been studied by means of microscopic follow-ups of transplants. These investigations were seriously handi capped by the fact that a great similarity existed in the microscopic picture between the host cornea and the graft. Furthermore, it is not known in which manner a total sub stitution occurs, if indeed it occurs at all. In vestigations with artificially induced scars do * From the University Eye Clinic. I wish to thank Dr. P. van der Meer, Dr. J. A. Cohen, Dr. H. L. Booy, Prof. P. J. Gaillard, Dr. G. J. Verdonck, and Mr. W. A. Blokhuis for their unstinted help and valuable discussions, and Mr. L. Beumer for his help in laboratory technique.
not sufficiently indicate the full regenerative potency of the cornea. These difficulties are overcome on implant ing a graft without a histologic structure, having the property of gradual absorption. In these circumstances it becomes possible to study the "pure" behavior of the host cornea, itself. Blood plasma was chosen as the "graft." It has no histologic structure and, if placed in the anterior chamber of the eye, was shown to dissolve in about a fortnight. Biochemi cally, however, plasma shows a definite struc ture; this is of possible value in the results of the implantation. The incorporation into tissue cultures of certain structures, such as threads of nylon or glass, and the influence of the highest tension in the underlying rubber-base much
702
G. W. H. M. VAN ALPHEN
Fig. 1 (van Alphen). Host cornea (to the left) and plasma graft four days after implantation. The graft is partially torn off. The proliferation of the host cornea's endothelium is continued over onto the graft (E-E). The epithelium has also proliferated, though rather less than the photograph would seem to indi cate. In the graft, remains of the plasma are still clearly visible, particularly in the form of bars. Note the migrated cells. improve the rate of cell migration ( W e i s s * ) . Since plasma has a fibrillar structure, a stimulating influence on cell migration may be expected.
first implantation was carried out following Castroviejo's method.1" From this experiment it became clear that the operation itself was feasible; since the anterior chamber was reformed and the graft did not dissolve too rapidly, the eye was preserved. Because the fixation sutures cut deeply into the soft plasma, however, all the next implantations were fixed by means of contact glasses. Six plastic contact glasses of different sizes were manufactured to fit rabbits' eyes. Prior to each operation the best-fitting glass was selected. The normal cornea was then trephined under atropine, and the plasma film was cut with the same trephine. The excised piece of plasma film was then inserted into the eye, a contact glass was placed upon it, and firm pressure was applied for one to two minutes. The plasma soon adhered to the borders of the cornea and, at the end of this time in most cases, the anterior chamber had reformed. Penicillin-atropine ointment was applied and the eyelid sutured.
PREPARATION OF PLASMA
Rabbit blood, obtained on puncture of the heart, is received into a tube over oxalate of sodium and centrifuged. The oxalated plasma is sucked up and precipitated at 37° C. with a quantity of CaCl 2 , such that the clotting-time passes a minimum. As this plasma contains calcium, another method was employed later on in which blood was centrifuged in ice-cooled paraffined tubes. Then the syneresis water is removed from the plasma clot by applying slight pressure. A good plasma film, nearly two mm. in thickness, is obtained in this way. IMPLANTATION
The cornea of a rabbit was totally tre phined (diameter 4.1 mm.) and a plasma film of the same diameter was inserted. The ♦Weiss, P . : Arch. f. Entw. Mechan., 116:438, 1929.
Fig. 2 (van Alphen). High-power view of Figure 1. Proliferation of endothelium at the edge of the host cornea's Descemet's membrane. 11 wish to thank Dr. C. Kok van Alphen for carrying out this first implantation, Dr. E. G. Wijngaarde for valuable assistance in the other experiments, and Mr. D. Laman for anesthesia.
PLASMA IMPLANTATIONS IN THE CORNEA
703
S U B S E Q U E N T COURSE
At the end of three days, in most cases, no details were visible, as the dissolving plasma clouds the contact glass. After six to eight days, the contact glass is removed and the graft shows a chalk-white colora tion. After 10 days the color of the graft has, more or less, the aspect of milky glass. O n the 12th to 16th day, small radial blood vessels appear, originating in the limbus in the direction of the graft and pene trating into the graft in only a few of the observed cases. These vessels disappear again in from four to eight days. Twelve to 24 days after operation, the borders of the graft start to become transparent, and this pro ceeds extremely slowly toward the center of the graft. In all, 32 rabbits were operated T h e results w e r e :
upon.
Lost (panophthalmia) 4 Enucleation within 25 days of implantation 6 Thick macula corneas 10 Thin macula corneas 12 The transparency may be tabulated as fol lows : Cleared up at the borders 10 Clear epithelium and but slight stroma cloudiness and cloudy Descemet's mem brane 5 Clear epithelium and stroma; Descemet's membrane still cloudy 2 The same but with a very slight central clouding of Descement's membrane .. 2 Absolutely transparent 0 In only five cases was the implanted plasma film obtained from the blood of the same rabbit on which it was later grafted. I n all other cases, the plasma was derived from an arbitrarily chosen rabbit. In the
Fig. 4 (van Alphen). Later phase of proliferation of the endothelium at the edge of the host's Descemet's membrane. Beginning of new Descemet formation (three to four weeks after implantation).
P il *<*
Fig. 3 (van Alphen). Enlarged part of the plasma graft of Figure 1. Migration of endothelial cells. results, however, no difference was notice able ; a retarded dissolving of the plasma of auto-implants in the anterior chamber was suggested by the longer duration of cloudi ness of the aqueous. T h e microscopic sections of the 28 im plantations show the manner in which the plasma is being "rebuilt" into normal cor nea. T h i s process and its variations will be summarized here.
704
G. W. H. M. VAN ALPHEN scopic sections of the plasma-implanted cor neas still clearly show the original prolifera tion of the endotheHum at the edges of the host's Descemet's membrane. The host cornea's epithelium also is pro liferating—though much less intensively than the endotheHum—and these epithelial Cells, four days after implantation, have already crossed over to the edges of the plasma graft. Numbers of these cells appear to come loose from the context of the epi thelium, and to swarm into the plasma in a similar manner. LATER COURSE
Fig. 5 (van Alphen). Beginning of new Descemet formation (three to four weeks after implan tation). The graft, four days after the implanta tion, is wholly filled with spindle-shaped cells, many of which show mitotic division. The indication of the origin of these cells is very clear indeed—endotheHum of the host cornea at the edge of Descemet's membrane has pro liferated enormously and these endotheHum cells are migrating into the plasma graft. These migrated cells completely correspond in shape, size, and structure to the cells of the original endotheHum. Nearly all micro-
Fig. 6 (van Alphen). Proliferation of the endothelium eight weeks after implantation. Note host's Descemet's membrane and newly formed Descemet's of the graft.
In the protoplasm of the spindle-shaped cells in the graft, after eight to 15 days, a distinct fibrillary structure appears, which is shown exclusively, at the beginning, in the Gomorry-stained specimens; and later also with the Weigert-Gieson staining method. In the same period many specimens also show the beginnings of lamellar forma tion and flattening of the cells. In a later phase—about eight weeks after implantation—the newly formed stroma is hardly to be distinguished from the stroma of the host cornea in many cases. The lamel lar structure, in about half the cases, shows slight to very distinct irregularities, due largely to inflammation which may be ac companied by ingrowing blood vessels. In the initial phases of the chronic proliferative inflammation, a strong mesenchymal proliferation occurs, which shows exudate, leukocytes, accumulation of histiocytes, mast cells, and phagocytic giant cells. In later phases all this results in a very irregularly built fibrous tissue. In the early phases the stroma of the host cornea is, in many cases, slightly infiltrated with leukocytes. The stroma cells situated in the near vicinity of the graft are con siderably swollen, but no signs of mitosis were ever observed. In half the number of cases, a newly formed intact endotheHum was found and, moreover, a newly formed Descemet's mem-
PLASMA IMPLANTATIONS IN THE CORNEA brane was present in six of the cases. This new Descemet's membrane is thinner and stains more faintly than the host Descemet's membrane. Apart from these findings in three of the seven eyes enucleated early in the experiment (three to four weeks after implantation), Descemet's membrane was present in a rudimentary form. In only four cases was the epithelium absent. All the other cases showed intact epitheliums, some of which were very reg ular, and others considerably irregular in appearance. In two cases, large bullae had formed. In one case, there was such a pro liferation of the epithelium that it resembled a granuloma.* Even three to four weeks after implanta tion, definite parts of the epithelium clearly indicated a gradual transition of epithelium cells into stroma cells. It is obvious that the epithelium takes its part in the building-up of the stroma, though to a much lesser ex tent than the endothelium. The time of epithelization of the surface of the graft varies considerably—between 12 and 30 days—being determined by means of fluorescein staining in the living eye. In one of the microscopic sections a very regular intact epithelium was found as early as 14 days after implantation. Bowman's membrane is absent in rabbits and it may be that its function is taken over by the basal membrane of the epithelium. In 10 cases the new epithelium showed a dis tinct basal membrane. A summary of microscopic findings in 22 eyes enucleated after more than three weeks following implantation shows:
70S
I .. 7 'van Alphen). The newly formed stroma, _'0 dajs after implantation. Migrating endothelial cells constitute a three-dimensional reticulum. STROMA
Regular Irregular Fibrous Vascularization
10 12 S S
DESCEMET'S MEMBRANE
Present Indicated
6 3
ENDOTHELIUM INTACT
11
SYNECHIAS (anterior)
7
EPITHELIUM
Absent Present Regular Irregular BASAL MEMBRANE
4 18 11 7 10
* In this case, in the newly formed stroma many cells resembling eosinophilic leukocytes were found, the significance of whicli remains obscure.
Fig. 8 (van Alphen). Gradual transition of epi thelial cells of the graft into stroma cells (three to four weeks after implantation).
706
G. W. H. M. VAN ALPHEN
4uW
CONCLUSIONS
F r o m experimental work on rabbits it be came clear that implantation of a plasma film into a wholly trephined normal cornea is possible; fixation being by means of a contact glass. It was shown that the host cornea is able to build up into this plasma medium a new tissue which very closely resembles the nor mal cornea in histologic structure and trans parency (a slight central clouding of Desce met's membrane excepted). The host cornea's endothelium appears to be essentially significant in the formation of
OPHTHALMIC
Fig. 9 (van Alphen). Host cor nea and newly formed cornea three months after implantation. The place of transition is marked by a slight irregularity in the lamellar structure of the stroma. Also the host's Descemet's membrane is thicker and stains more deeply than the newly formed Descemet. Re mains of proliferation of the endothelium.
stroma, Descemet's membrane, and the new endothelium. T h e new epithelium is derived from the host cornea's epithelium, the proliferation of which may also be of some significance in the stroma formation, though its share seems to be rather slight. These investigations appear to be of theoretical value only, in so far as they in dicate the potency of the host cornea, the possibility of corneal regeneration in a proper medium, and the manner in which this re generation takes place. University
Eye
Clinic.
MINIATURE
W h e n the adhesion (symblepharon) begins at, is continuous with, and arises from that part of the conjunctiva which is reflected from the lid to the ball of the eye, so that on raising the eyelid a broad attachment is perceived, restraining the motions of the eye, it ought not to be meddled with for it may be increased, but it will never be diminished. Guthrie, Lecture on the Operative Surgery of the Eye, 1830.