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Retinal Vein Occlusion:*
AMERICAN JOURNAL VOLUME
OF
OPHTHALMOLOGY
MAY, 1951
34
NUMBER 5, PART I
R E T I N A L VEIN OCCLUSION* C L I N I C A L A N D E X P E R I M E N T A L OBSERVATIONS BERNARD B E C K E R , M.D.,
AND L A W R E N C E T .
POST, JR.,
M.D.
Baltimore, Maryland
The recent work on the vascular pathology of diabetic retinopathy1 indicates a striking similarity between this disease and two others: Eales's disease and central vein oc clusion. An experimental investigation of certain phases of these diseases was there fore undertaken in the hope that some more concrete evidence of this similarity might be discovered. Specifically, in view of the demonstration of aneurysms2 in the retinal capillaries in diabetic retinopathy, it was thought likely that aneurysms of similar nature might be present in cases of central vein occlusion and Eales's disease. With this in mind, all cases of vein occlusion in the clinical and patho logic files of the Wilmer Institute were re viewed, and the possibility of producing central vein occlusion in the experimental animal was explored. I. CLINICAL
In order to compare statistics, the litera ture on venous occlusion was reviewed, and from this review certain generalizations are in order. Although, soon after the invention of the ophthalmoscope, central vein occlusion was illustrated in the ophthalmologic atlases, its essential nature was not described until the report of Michel3 in 1878. He believed that the majority of such occlusions were * From the Wilmer Ophthalmological Institute of The Johns Hopkins University and Hospital. Pre sented at the ninth annual meeting of the Wilmer Residents Association, April, 1950. 677
caused by thrombosis, but he described one case in which no thrombus could be found and in which intimal proliferation seemed to play an important part. There followed a series of papers by Coats4 and VerhoefF in which this contro versy was intensified and never really satis factorily resolved. Coats contended that most cases were due to thrombosis, while Ver hoefF was equally sure that they were due to endothelial proliferation. With the publication of several papers by Scheerer6 in the early twenties, the enthusi asts for intimal proliferation seemed to be in the ascendency, but with the advent of anti coagulants, it became immediately apparent that the idea of thrombosis still had its large group of adherents. Suffice it to say that at present there is still no real agreement, and it is not our intention to enter into this de bate. This study, however, brought out several less frequently discussed points which ap pear worth emphasizing. In the files of the Wilmer Institute, there were over 150 diag noses of vein occlusion, but because of in complete records only 59 eyes in 57 patients were suitable for analysis. This material con sisted of 15 branch occlusions and 44 central occlusions. The study was also limited by the fact that the diagnostic index of the Wilmer Institute is limited to patients ad mitted to the hospital; out-patient diagnoses are not indexed. Therefore, the cases of central vein occlusion included in this series are almost exclusively either of the patients
678
BERNARD BECKER AND LAWRENCE T. POST, JR.
with glaucoma, or of those admitted for diag nostic surveys. Seven of the branch occlusions were in the superior temporal vein, five in the inferior temporal vein, and only one was an isolated nasal branch occlusion. This is in good agreement with the large series reported by Foster Moore,7 Jensen,8 Koyanagi,9 and Allaire,10 whose over-all statistics revealed 87 (65 percent) superior temporal, 40 (30 per cent) inferior temporal, and only two isoata4»iiasal occlusions. Gftadle,11 Duke-Elder,12 and others have been impressed with the frequency with which vein occlusion occurs in cases with preexisting glaucoma. In 1913, VerhoefP3 reviewed the pathology of 39 cases of glau coma secondary to anterior segment disease and discovered that in all of these cases there was endovasculitis in either one or both of the central vessels; 83 p»fcent of the central veins showed endophlebrtis, and 33 percent of the cases showed either partial or com plete obstruction of the central retinal vein. Tn the various clinical flBDrts there has been a similar high percentage of cases oc curring in primary and mor« frequently in secondary glaucoma. In this scries, in 10 of 44, or 23 percent, of the central vein occlu sions and in one of the 15 branch occlusions, the occlusion was preceded by an elevated ocular tension. A review of the literature suggests two distinct types of glaucoma occurring in eyes with vein occlusion; first, an acute, hemorrhagic glaucoma following a latent period, characterized by rubeosis iridis, high tension, and an extremely poor prognosis; and secondly, a less dramatic, more benign glau coma, without rubeosis, nonhemorrhagic, without a characteristic latent period, and without acute onset.14 The cases in this series tend to bear out the apparent fact that the latter type is not secondary to the vein occlusion, but that either the glaucoma precedes and is responsi ble itself for the occlusion, or that glaucoma
and occlusions tend to occur in eyes with similar vascular disturbances. A nice illustration is afforded by two of the patients in this series who developed central vein occlusion superimposed on glau coma simplex, and who later, after an ap propriate latent period, had a sudden, addi tional increase in tension, developed rubeosis, pain, and eventually came to the inevitable loss of the eye. The general prognosis in branch occlusion in all reported cases is a tendency to im provement over a period of years without the development of glaucoma. There are only two cases of hemorrhagic glaucoma second ary to branch occlusion reported in the litera ture. One of these is reported by Uhtoff15 in which no details are given, and one by Jensen,8 which from the history appears to have been in all probability a case of central vein occlusion. Apparently, therefore, hem orrhagic glaucoma does not occur secondary to a branch occlusion. The prognosis in central vein occlusion is poor, with a tendency to steady deterioration of the eye. Ten to 20 percent of these pa tients develop hemorrhagic glaucoma, and these seem to have a particularly dismal out look. In this series all eyes with true hemor rhagic glaucoma secondary to vein occlusion came eventually to enucleation. II.
PATHOLOGIC
In fundus pictures of "retinal apoplexy" in the early atlases, small aneurysmal dilations of the vessels are clearly depicted. Coats18 mentioned "miliary angiomata" in his patho logic descriptions. Recently these lesions, which previously had been alluded to only indefinitely, were established on a firmer foun dation when Loewenstein17 published his de scription in 1945 «f capillary aneurysms and demonstrated them by scarlet-red staining of flat preparations of the retina. We have re cently become aware that work similar to ours on flat preparations of the retina is being car ried out by Ballantyne18 and his associates in
RETINAL VEIN OCCLUSION
679
Fig. 1 (Becker and Post). Typical chains of sac cular aneurysms on the venous side of the capillary circulation in central vein occlusion. Note the tre mendously dilated aneurysms as compared with the size of the surrounding relatively normal capillaries.
Fig. 2 (Becker and Post). An isolated, thickwalled, saccular aneurysm in central vein occlusion. There are surrounding exudates and deformity of the capillary pattern, probably representing newly formed vessels.
Fig. 3-A (Becker and Post). Chain of aneurysms in a case of central vein occlusion.
Fig. 3-B (Becker and Post). High-power view of one of the aneurysms in Figure 3-A.
680
BERNARD BECKER AND LAWRENCE T. POST, JR. Glasgow, Scotland, with similar results. Flat preparations of retinas, when stained for polysaccharides by the Hotchkiss method, reveal the intimate details of the vascular and in particular the capillary net work.1 Since this method has proved to be so profitable in the demonstration of the capillary aneurysms of diabetic retinopathy, it seemed reasonable to apply this technique
Fig. 4 (Becker and Post). Marked distortion of capillaries, with large, dense aneurysms and exudates in a case of central vein occlusion.
Fig. 6 (Becker and Post). Distortion of the vas cular pattern with newly formed capillaries on the surface of the retina in a case of central vein occlusion. to cases of Eales's disease and central vein occlusion.* To date 39 cases of central vein occlusion * Preliminary incubation of eyes at room tem perature for 24 to 36 hours before fixation has proved most valuable in obtaining better differen tiation of the capillaries, which survive the more rapid autolysis of the rods and cones.
Fig. 5 (Becker and Post). Flat preparation from a case of diabetes with marked diabetic retinopathy in which many large, thick-walled aneurysms in clusters were found throughout the retina in all
parts of the capillaries. The photograph represents one area in that retina in which there are chains of aneurysms as well as large, isolated aneurysms. This may represent a superimposed, small branch venous occlusion.
RETINAL VEIN OCCLUSION
681
selected from the files of the pathology labo ratory of the Wilmer Institute have been studied, all patients with diabetes being ex cluded. This of necessity has limited the ma terial to eyes which were enucleated for hemorrhagic glaucoma in patients in whom there was a definite history of central vein occlusion or actual observation of occlusion some weeks or months before.
Fig. 8 (Becker and Post). Tremendous distortion of the capillaries, which are folded and twisted on themselves and in a plane anterior to that of the retina. Aneurysms are also present in this case of central vein occlusion.
Fig. 7 (Becker and Post). Aneurysms with dis tortion and newly formed capillaries in central vein occlusion.
Six of the cases, however, were found as chance findings at routine autopsy with no history or evidence of glaucoma. In each of these 39 cases of central vein occlusion, capil lary aneurysms were found. It is, of course, conceivable that some of these cases had undiagnosed diabetes, but the findings were consistent in all cases, and in many there were definite records of the absence of glycosuria and the presence of normal fast ing blood sugars, and in several there were normal glucose tolerance curves. The most consistent and typical type of deformity of the capillaries that was ob-
Fig. 9 (Becker and Post). A coiled capillary pro truding forward into the vitreous which appears collapsed onto the surface of the retina in this preparation from a case of central vein occlusion.
682
BERNARD BECKER AND LAWRENCE T. POST, JR. served in these cases of central vein occlu sion was chains of saccular aneurysms on the venous side of the capillary circulation (figs. 1 and 3 ) . I n some instances isolated, thick-walled, saccular aneurysms of a type quite similar to those found in diabetes were found, but they were invariably confined to the venous end of the capillary (figs. 2 and 5 ) . Hemorrhages and exudates surrounded, and were closely associated with, the microaneurysms (figs. 2 and 4 ) . Remarkable dis tortion of capillary architecture and newlyformed capillaries on the surface of the retina (retinitis proliferans) were found frequently (figs. 6, 7, 8, and 9 ) .
Fig. 10-A (Becker and Post). An isolated aneurysm in a flat preparation of the retina from a case of Eales's disease. In this case there was con siderable retinal edema, hemorrhages, and retinitis proliferans, and therefore, the preparation is not well differentiated.
Fig. 11 (Becker and Post). Diagrammatic repre sentation of method utilized to produce experi mental venous occlusion. In the one case of Eales's disease so far investigated, both isolated aneurysms and chains of aneurysms were found (fig. 10). III.
Fig. 10-B (Becker and Post). Chains of aneu rysms in another area of the retina in the same case of Eales's disease as is shown in Figure 10-A.
EXPERIMENTAL
Various forms of therapy and innumer able theories as to the pathogenesis of dia betic retinopathy, central vein occlusion, and Eales's disease have been proposed. It seemed possible, therefore, that considerable information on the pathogenesis and therapy of this group of diseases might be obtained if a method could be devised for producing
RETINAL VEIN OCCLUSION
683
such lesions in animals. Attempts have been made to produce diabetic retinopathy in rab bits made diabetic with alloxan, but thus far without success. W e wish to describe a technique for occluding retinal veins and to present preliminary observations and re sults. Rabbits were first used, but because of their inadequate retinal circulation it was
Fig. 13-B (Becker and Post). High-power view of thrombosed vessels in Figure 13-A. Note the fibroblasts growing into the thrombus.
Fig. 13-A (Becker and Post). Organizing thrombi in central vein of cat's retina 10 days fol lowing experimental occlusion. necessary to change to cats. A 120 micron "nichrome" wire was utilized that was insu lated except at its tip, which was filed smooth. One end of the wire was attached to the diathermy machine and the other introduced into the eye at the pars plana of the ciliary body or in the peripheral retina, after pre liminary cauterization and diathermy to the surrounding area of sclera. U n d e r direct ob servation with an ophthalmoscope (fig. 11), the wire could be directed back through the vitreous until it was in the deep cup of the optic nerve. In the normal cat fundus there are three
Fig. 14 (Becker and Post). Relatively normal artery with a thrombosed vein next to it near the disc in a cat's retina 10 days following experimental occlusion. Note the phagocytized blood pigment.
684
BERNARD BECKER AND LAWRENCE T. POST, JR.
Fig. IS-A (Becker and Post). Thrombosed vessel with beginning recanalization in a cat's retina fol lowing venous occlusion.
Fig. 16 (Becker and Post). Isolated, thick-walled aneurysm in a flat preparation of the retina of a cat three months following experimental occlusion.
Fig. 1S-B (Becker and Post). High-power view of Figure 15-A.
Fig. 17 (Becker and Post). Isolated aneurysms as well as chains of capillary aneurysms in the retina of a cat three months following experimental venous occlusion.
RETINAL VEIN OCCLUSION
685
branches of the central retinal artery and vein (superior temporal, inferior temporal, and nasal) and seven to 10 smaller cilioretinal arterioles coming off the deeply cup ped disc.19
Fig. 19 (Becker and Post). Capillary aneurysms in cat's retina following experimental venous oc clusion.
Fig. 18 (Becker and Post). Isolated, thick-walled aneurysm and distortion of capillary pattern in flat preparation of cat's retina after venous occlusion.
With the electrode in the cup but touch ing no vessels, a standard current was ap plied for 10 seconds. There was immediate liberation of gas bubbles in the vitreous as a result of the heat at the tip of the electrode, as well as constriction of arterioles and marked dilation of the veins. In successful cases no hemorrhages or exudates were visible at the close of the pro cedure. Fifteen to 20 hours later, however, hemorrhages and exudates were noted be ginning in the far periphery. These increased in number, and in two to three days the fundi showed relatively normal arteries, dilated, tortuous veins associated with exudates, and large, flame-shaped hemor rhages, retinal edema, capillary aneurysms, round hemorrhages, and occasional hemor-
Fig. 20 (Becker and Post). Marked distortion of capillary pattern with giant aneurysm in flat prepa ration of cat's retina two months after experimental venous occlusion.
686
BERNARD BECKER AND LAWRENCE T. POST, JR.
rhages into the vitreous. This picture closely simulated clinical vein occlusion. Attempts to photograph cat fundi met with little success. W e are indebted to M r s . Burgess for her excellent painting of the fundus of a cat 10 days following operation (fig. 12). Serial sections of such eyes revealed hem orrhages, exudates, and venous thrombi which became organized and recanalized. In spite of intensive search no abnormalities in the choroid or in the disc itself could be found (figs. 13, 14, and 15). In order to determine if these induced venous occlusions would compare patho logically with those occurring in humans, the basement membrane stain for flat prepara tions was modified to permit its use on ani mal retinas.* By means of this technique, isolated capillary aneurysms, chains of aneurysms at the venous end of capillaries, distortion of capillary architecture, and newly formed vessels could be clearly demonstrated (figs. 16, 17, 18, 19, and 2 0 ) . While no conclusions can be drawn from these preliminary observations, they appear to indicate some similarity in the vascular pathology of diabetic retinopathy and central vein occlusion.
SUMMARY
1. T h e literature and the cases of central vein occlusion in the Wilmer Ophthalmological Institute are reviewed. 2. Branch occlusions in almost all cases are seen clinically in the temporal and especially superior temporal veins and are apparently never followed by hemorrhagic glaucoma. 3. Central vein occlusion is more common in patients with chronic glaucoma. 4. Hemorrhagic glaucoma secondary to central vein occlusion has a uniformly hope less prognosis. 5. Paravenous chains of saccular capil lary aneurysms are demonstrated in cases of central vein occlusion and Eales's disease, which simulate those of diabetic retinopathy but, on the whole, differ in the part of the capillary affected, the location in the retina, and their general appearance. 6. A technique is described for producing a picture in animals which clinically simu lates central vein occlusion and pathologi cally exhibits vein thrombosis and venous capillary aneurysms. The Johns Hopkins Hospital (5). * Sec footnote on page 680.
REFERENCES
1. Friedenwald, J. S.: Am. J. Ophth., 32 :487,1949. 2. Mackenzie, S.: Roy. London Ophth. Hosp. Rep., 9 :134, 1877. 3. Michel, J.: Graefe's Arch. f. Ophth., 24:37 (Part II) 1878. 4. Coats: Roy. London Ophth. Hosp. Rep., 16:62, 1904; 16:516, 1906; Tr. Ophth. Soc. U. Kingdom, 24:161,1904; 33:30,1913. 5. Vcrhoeff, F.: Ophth. Rev., 25:353, 1906; Arch. Ophth., 36:1, 1907; Discussion of paper by MacDonald : Tr. Am. Ophth. Soc, 38 :321, 1940. 6. Scheerer: Graefe's Arch. Ophth., 112:206, 1923. 7. Moore, F.: Brit. J. Ophth., Suppl. II, 1924. 8. Jensen, V. A.: Acta Ophth., 14 :Suppl. X, 1936. 9. Koyanagi: Klin. Monatsbl. f. Augenh., 81 :219, 1928. 10. Allaire, J.: Contribution a l'etude des hemorragies de la retine. Paris, 1925. 11. Gradle, H. S.: Am. J. Ophth, 20:1125, 1937. 12. Duke-Elder, W. S.: Textbook of Ophthalmology, St. Louis, Mosby, 1941, p. 2584. 13. Vcrhoeff: Arch. Ophth, 42:145, 1913. 14. Sugar : Arch. Ophth, 28 :587, 1942. 15. Uhtoff: Ber. d. deutschen Ophth. Gesell, Heidelberg, 45 :65, 1925. 16. Coats : Tr. Ophth. Soc. U. Kingdom, 33 :30, 1913. 17. Loewenstein, A, and Garrow, A.: Am. J. Ophth, 28:840, 1945. 18. Ballantyne, A. J , and Michaelson, I. C.: Tr. Ophth. Soc. U. Kingdom, 67 :59, 1947. 19. Porsaa, Kaj.: Acta Ophth, Suppl. xviii-xix, 1941.
OF
OPHTHALMOLOGY
MAY, 1951
34
NUMBER 5, PART I
R E T I N A L VEIN OCCLUSION* C L I N I C A L A N D E X P E R I M E N T A L OBSERVATIONS BERNARD B E C K E R , M.D.,
AND L A W R E N C E T .
POST, JR.,
M.D.
Baltimore, Maryland
The recent work on the vascular pathology of diabetic retinopathy1 indicates a striking similarity between this disease and two others: Eales's disease and central vein oc clusion. An experimental investigation of certain phases of these diseases was there fore undertaken in the hope that some more concrete evidence of this similarity might be discovered. Specifically, in view of the demonstration of aneurysms2 in the retinal capillaries in diabetic retinopathy, it was thought likely that aneurysms of similar nature might be present in cases of central vein occlusion and Eales's disease. With this in mind, all cases of vein occlusion in the clinical and patho logic files of the Wilmer Institute were re viewed, and the possibility of producing central vein occlusion in the experimental animal was explored. I. CLINICAL
In order to compare statistics, the litera ture on venous occlusion was reviewed, and from this review certain generalizations are in order. Although, soon after the invention of the ophthalmoscope, central vein occlusion was illustrated in the ophthalmologic atlases, its essential nature was not described until the report of Michel3 in 1878. He believed that the majority of such occlusions were * From the Wilmer Ophthalmological Institute of The Johns Hopkins University and Hospital. Pre sented at the ninth annual meeting of the Wilmer Residents Association, April, 1950. 677
caused by thrombosis, but he described one case in which no thrombus could be found and in which intimal proliferation seemed to play an important part. There followed a series of papers by Coats4 and VerhoefF in which this contro versy was intensified and never really satis factorily resolved. Coats contended that most cases were due to thrombosis, while Ver hoefF was equally sure that they were due to endothelial proliferation. With the publication of several papers by Scheerer6 in the early twenties, the enthusi asts for intimal proliferation seemed to be in the ascendency, but with the advent of anti coagulants, it became immediately apparent that the idea of thrombosis still had its large group of adherents. Suffice it to say that at present there is still no real agreement, and it is not our intention to enter into this de bate. This study, however, brought out several less frequently discussed points which ap pear worth emphasizing. In the files of the Wilmer Institute, there were over 150 diag noses of vein occlusion, but because of in complete records only 59 eyes in 57 patients were suitable for analysis. This material con sisted of 15 branch occlusions and 44 central occlusions. The study was also limited by the fact that the diagnostic index of the Wilmer Institute is limited to patients ad mitted to the hospital; out-patient diagnoses are not indexed. Therefore, the cases of central vein occlusion included in this series are almost exclusively either of the patients
678
BERNARD BECKER AND LAWRENCE T. POST, JR.
with glaucoma, or of those admitted for diag nostic surveys. Seven of the branch occlusions were in the superior temporal vein, five in the inferior temporal vein, and only one was an isolated nasal branch occlusion. This is in good agreement with the large series reported by Foster Moore,7 Jensen,8 Koyanagi,9 and Allaire,10 whose over-all statistics revealed 87 (65 percent) superior temporal, 40 (30 per cent) inferior temporal, and only two isoata4»iiasal occlusions. Gftadle,11 Duke-Elder,12 and others have been impressed with the frequency with which vein occlusion occurs in cases with preexisting glaucoma. In 1913, VerhoefP3 reviewed the pathology of 39 cases of glau coma secondary to anterior segment disease and discovered that in all of these cases there was endovasculitis in either one or both of the central vessels; 83 p»fcent of the central veins showed endophlebrtis, and 33 percent of the cases showed either partial or com plete obstruction of the central retinal vein. Tn the various clinical flBDrts there has been a similar high percentage of cases oc curring in primary and mor« frequently in secondary glaucoma. In this scries, in 10 of 44, or 23 percent, of the central vein occlu sions and in one of the 15 branch occlusions, the occlusion was preceded by an elevated ocular tension. A review of the literature suggests two distinct types of glaucoma occurring in eyes with vein occlusion; first, an acute, hemorrhagic glaucoma following a latent period, characterized by rubeosis iridis, high tension, and an extremely poor prognosis; and secondly, a less dramatic, more benign glau coma, without rubeosis, nonhemorrhagic, without a characteristic latent period, and without acute onset.14 The cases in this series tend to bear out the apparent fact that the latter type is not secondary to the vein occlusion, but that either the glaucoma precedes and is responsi ble itself for the occlusion, or that glaucoma
and occlusions tend to occur in eyes with similar vascular disturbances. A nice illustration is afforded by two of the patients in this series who developed central vein occlusion superimposed on glau coma simplex, and who later, after an ap propriate latent period, had a sudden, addi tional increase in tension, developed rubeosis, pain, and eventually came to the inevitable loss of the eye. The general prognosis in branch occlusion in all reported cases is a tendency to im provement over a period of years without the development of glaucoma. There are only two cases of hemorrhagic glaucoma second ary to branch occlusion reported in the litera ture. One of these is reported by Uhtoff15 in which no details are given, and one by Jensen,8 which from the history appears to have been in all probability a case of central vein occlusion. Apparently, therefore, hem orrhagic glaucoma does not occur secondary to a branch occlusion. The prognosis in central vein occlusion is poor, with a tendency to steady deterioration of the eye. Ten to 20 percent of these pa tients develop hemorrhagic glaucoma, and these seem to have a particularly dismal out look. In this series all eyes with true hemor rhagic glaucoma secondary to vein occlusion came eventually to enucleation. II.
PATHOLOGIC
In fundus pictures of "retinal apoplexy" in the early atlases, small aneurysmal dilations of the vessels are clearly depicted. Coats18 mentioned "miliary angiomata" in his patho logic descriptions. Recently these lesions, which previously had been alluded to only indefinitely, were established on a firmer foun dation when Loewenstein17 published his de scription in 1945 «f capillary aneurysms and demonstrated them by scarlet-red staining of flat preparations of the retina. We have re cently become aware that work similar to ours on flat preparations of the retina is being car ried out by Ballantyne18 and his associates in
RETINAL VEIN OCCLUSION
679
Fig. 1 (Becker and Post). Typical chains of sac cular aneurysms on the venous side of the capillary circulation in central vein occlusion. Note the tre mendously dilated aneurysms as compared with the size of the surrounding relatively normal capillaries.
Fig. 2 (Becker and Post). An isolated, thickwalled, saccular aneurysm in central vein occlusion. There are surrounding exudates and deformity of the capillary pattern, probably representing newly formed vessels.
Fig. 3-A (Becker and Post). Chain of aneurysms in a case of central vein occlusion.
Fig. 3-B (Becker and Post). High-power view of one of the aneurysms in Figure 3-A.
680
BERNARD BECKER AND LAWRENCE T. POST, JR. Glasgow, Scotland, with similar results. Flat preparations of retinas, when stained for polysaccharides by the Hotchkiss method, reveal the intimate details of the vascular and in particular the capillary net work.1 Since this method has proved to be so profitable in the demonstration of the capillary aneurysms of diabetic retinopathy, it seemed reasonable to apply this technique
Fig. 4 (Becker and Post). Marked distortion of capillaries, with large, dense aneurysms and exudates in a case of central vein occlusion.
Fig. 6 (Becker and Post). Distortion of the vas cular pattern with newly formed capillaries on the surface of the retina in a case of central vein occlusion. to cases of Eales's disease and central vein occlusion.* To date 39 cases of central vein occlusion * Preliminary incubation of eyes at room tem perature for 24 to 36 hours before fixation has proved most valuable in obtaining better differen tiation of the capillaries, which survive the more rapid autolysis of the rods and cones.
Fig. 5 (Becker and Post). Flat preparation from a case of diabetes with marked diabetic retinopathy in which many large, thick-walled aneurysms in clusters were found throughout the retina in all
parts of the capillaries. The photograph represents one area in that retina in which there are chains of aneurysms as well as large, isolated aneurysms. This may represent a superimposed, small branch venous occlusion.
RETINAL VEIN OCCLUSION
681
selected from the files of the pathology labo ratory of the Wilmer Institute have been studied, all patients with diabetes being ex cluded. This of necessity has limited the ma terial to eyes which were enucleated for hemorrhagic glaucoma in patients in whom there was a definite history of central vein occlusion or actual observation of occlusion some weeks or months before.
Fig. 8 (Becker and Post). Tremendous distortion of the capillaries, which are folded and twisted on themselves and in a plane anterior to that of the retina. Aneurysms are also present in this case of central vein occlusion.
Fig. 7 (Becker and Post). Aneurysms with dis tortion and newly formed capillaries in central vein occlusion.
Six of the cases, however, were found as chance findings at routine autopsy with no history or evidence of glaucoma. In each of these 39 cases of central vein occlusion, capil lary aneurysms were found. It is, of course, conceivable that some of these cases had undiagnosed diabetes, but the findings were consistent in all cases, and in many there were definite records of the absence of glycosuria and the presence of normal fast ing blood sugars, and in several there were normal glucose tolerance curves. The most consistent and typical type of deformity of the capillaries that was ob-
Fig. 9 (Becker and Post). A coiled capillary pro truding forward into the vitreous which appears collapsed onto the surface of the retina in this preparation from a case of central vein occlusion.
682
BERNARD BECKER AND LAWRENCE T. POST, JR. served in these cases of central vein occlu sion was chains of saccular aneurysms on the venous side of the capillary circulation (figs. 1 and 3 ) . I n some instances isolated, thick-walled, saccular aneurysms of a type quite similar to those found in diabetes were found, but they were invariably confined to the venous end of the capillary (figs. 2 and 5 ) . Hemorrhages and exudates surrounded, and were closely associated with, the microaneurysms (figs. 2 and 4 ) . Remarkable dis tortion of capillary architecture and newlyformed capillaries on the surface of the retina (retinitis proliferans) were found frequently (figs. 6, 7, 8, and 9 ) .
Fig. 10-A (Becker and Post). An isolated aneurysm in a flat preparation of the retina from a case of Eales's disease. In this case there was con siderable retinal edema, hemorrhages, and retinitis proliferans, and therefore, the preparation is not well differentiated.
Fig. 11 (Becker and Post). Diagrammatic repre sentation of method utilized to produce experi mental venous occlusion. In the one case of Eales's disease so far investigated, both isolated aneurysms and chains of aneurysms were found (fig. 10). III.
Fig. 10-B (Becker and Post). Chains of aneu rysms in another area of the retina in the same case of Eales's disease as is shown in Figure 10-A.
EXPERIMENTAL
Various forms of therapy and innumer able theories as to the pathogenesis of dia betic retinopathy, central vein occlusion, and Eales's disease have been proposed. It seemed possible, therefore, that considerable information on the pathogenesis and therapy of this group of diseases might be obtained if a method could be devised for producing
RETINAL VEIN OCCLUSION
683
such lesions in animals. Attempts have been made to produce diabetic retinopathy in rab bits made diabetic with alloxan, but thus far without success. W e wish to describe a technique for occluding retinal veins and to present preliminary observations and re sults. Rabbits were first used, but because of their inadequate retinal circulation it was
Fig. 13-B (Becker and Post). High-power view of thrombosed vessels in Figure 13-A. Note the fibroblasts growing into the thrombus.
Fig. 13-A (Becker and Post). Organizing thrombi in central vein of cat's retina 10 days fol lowing experimental occlusion. necessary to change to cats. A 120 micron "nichrome" wire was utilized that was insu lated except at its tip, which was filed smooth. One end of the wire was attached to the diathermy machine and the other introduced into the eye at the pars plana of the ciliary body or in the peripheral retina, after pre liminary cauterization and diathermy to the surrounding area of sclera. U n d e r direct ob servation with an ophthalmoscope (fig. 11), the wire could be directed back through the vitreous until it was in the deep cup of the optic nerve. In the normal cat fundus there are three
Fig. 14 (Becker and Post). Relatively normal artery with a thrombosed vein next to it near the disc in a cat's retina 10 days following experimental occlusion. Note the phagocytized blood pigment.
684
BERNARD BECKER AND LAWRENCE T. POST, JR.
Fig. IS-A (Becker and Post). Thrombosed vessel with beginning recanalization in a cat's retina fol lowing venous occlusion.
Fig. 16 (Becker and Post). Isolated, thick-walled aneurysm in a flat preparation of the retina of a cat three months following experimental occlusion.
Fig. 1S-B (Becker and Post). High-power view of Figure 15-A.
Fig. 17 (Becker and Post). Isolated aneurysms as well as chains of capillary aneurysms in the retina of a cat three months following experimental venous occlusion.
RETINAL VEIN OCCLUSION
685
branches of the central retinal artery and vein (superior temporal, inferior temporal, and nasal) and seven to 10 smaller cilioretinal arterioles coming off the deeply cup ped disc.19
Fig. 19 (Becker and Post). Capillary aneurysms in cat's retina following experimental venous oc clusion.
Fig. 18 (Becker and Post). Isolated, thick-walled aneurysm and distortion of capillary pattern in flat preparation of cat's retina after venous occlusion.
With the electrode in the cup but touch ing no vessels, a standard current was ap plied for 10 seconds. There was immediate liberation of gas bubbles in the vitreous as a result of the heat at the tip of the electrode, as well as constriction of arterioles and marked dilation of the veins. In successful cases no hemorrhages or exudates were visible at the close of the pro cedure. Fifteen to 20 hours later, however, hemorrhages and exudates were noted be ginning in the far periphery. These increased in number, and in two to three days the fundi showed relatively normal arteries, dilated, tortuous veins associated with exudates, and large, flame-shaped hemor rhages, retinal edema, capillary aneurysms, round hemorrhages, and occasional hemor-
Fig. 20 (Becker and Post). Marked distortion of capillary pattern with giant aneurysm in flat prepa ration of cat's retina two months after experimental venous occlusion.
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rhages into the vitreous. This picture closely simulated clinical vein occlusion. Attempts to photograph cat fundi met with little success. W e are indebted to M r s . Burgess for her excellent painting of the fundus of a cat 10 days following operation (fig. 12). Serial sections of such eyes revealed hem orrhages, exudates, and venous thrombi which became organized and recanalized. In spite of intensive search no abnormalities in the choroid or in the disc itself could be found (figs. 13, 14, and 15). In order to determine if these induced venous occlusions would compare patho logically with those occurring in humans, the basement membrane stain for flat prepara tions was modified to permit its use on ani mal retinas.* By means of this technique, isolated capillary aneurysms, chains of aneurysms at the venous end of capillaries, distortion of capillary architecture, and newly formed vessels could be clearly demonstrated (figs. 16, 17, 18, 19, and 2 0 ) . While no conclusions can be drawn from these preliminary observations, they appear to indicate some similarity in the vascular pathology of diabetic retinopathy and central vein occlusion.
SUMMARY
1. T h e literature and the cases of central vein occlusion in the Wilmer Ophthalmological Institute are reviewed. 2. Branch occlusions in almost all cases are seen clinically in the temporal and especially superior temporal veins and are apparently never followed by hemorrhagic glaucoma. 3. Central vein occlusion is more common in patients with chronic glaucoma. 4. Hemorrhagic glaucoma secondary to central vein occlusion has a uniformly hope less prognosis. 5. Paravenous chains of saccular capil lary aneurysms are demonstrated in cases of central vein occlusion and Eales's disease, which simulate those of diabetic retinopathy but, on the whole, differ in the part of the capillary affected, the location in the retina, and their general appearance. 6. A technique is described for producing a picture in animals which clinically simu lates central vein occlusion and pathologi cally exhibits vein thrombosis and venous capillary aneurysms. The Johns Hopkins Hospital (5). * Sec footnote on page 680.
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