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STUDY OF THE PATHOLOGIC CHANGES IN THE OPTIC NERVES AND CHIASM IN COMPARISON WITH CHANGES IN THE IN ASSO- CIATION WITH LARGE PITUITARY TUMORS* WALTER I. LILLIE, M.D. Rochester, Minnesota The ophthalmologic syndromes produced by lesions near -or at the have been well described and definitely established by many authors, but studies of the pathologic changes in the optic nerves and chiasm, and attempts to correlate these with defects in the visual field, are much less numerous. This is true especially when the causative factor is restricted to pituitary tumors. For this reason I studied four cases of extraordinarily large pituitary tumor in which necropsy was performed. These cases were chosen because the bitemporal hemianopic defects in the fields could be correlated with the pathologic changes in the optic nerves and chiasm. The ocular symptoms and signs produced by pituitary tumors may be summarized as follows: (1) Lowered central visual acuity; (2) pallor of the optic discs or simple optic atrophy; (3) bitemporal for various colors or for all colors; (4) for form and colors; (5) bitemporal scotomatous hemianopsia for colors or form or for both; (6) temporal hemianopsia with amaur- osis of the opposite eye; (7) temporal hemianopsia with successive changes that lead to amaurosis, such as central , cecocentral scotoma, enlargement of the scotoma, with islets of vision and amaurosis; (8) homonymous herni- * From the Section on , The Mayo Clinic, Rochester, Minnesota. Candidate's thesis for membership accepted by the Committee on Theses. 15 433 434 LILLIE: Changes in Optic Nerves and Chiasm anopic scotoma for colors or form or for both; (9) homony- mous hemianopsia for colors, and (10) homonymous hemian- opsia for form and colors. An important feature of the defects in the visual fields produced by pituitary tumors is the asymmetry,-whether bitemporal or homonymous in type,-in contrast to the sym- metrical defects produced by lesions which affect the optic tracts or optic radiations. This can readily be explained by the anatomic variations in the position of the optic chiasm in relation to the pituitary gland. This was reviewed by Fisherand byTraquair, and later summarized and enlarged on by de Schweinitz, who called attention to the thorough ana- tomic investigations of Schaeffer, which were published later. The earliest visual defects produced by pituitary tumors are found in the cecocentral region. They have been well described by Josefson, Fisher, Traquair, Wilbrand and Saenger, Cushing and Walker, Hill, Ronne, de Schweinitz, and Lillie. These defects have been variously described as "zones of deadened perception," paracentral , en- larged blind spots, and cecocentral scotomas, but Traquair's expression that the scotomas "behave like the general field" best describes these changes. The behavior of the general field was clearly established by Josefson, Fisher, and Cush- ing and Walker, working independently of one another. Although the central visual pathways were well estab- lished by Henschen, it was not until Walker and Cushing made detailed studies of the pathologic changes in the that correlation of the defects in the visual field and the pathologic changes in the optic nerve was attempted in chiasmal lesions. Their conclusions were: "1, Despite the so-called atrophic pallor -of the discs in patients having visual-field defects resulting from lesions in the chiasmal regions, the histologic examination of the nerves fails to show the expected degree of fiber degeneration unless the process has been of long duration; 2, the atrophy in the tracts LILLIE: Changes in Optic Nerves and Chiasm 435 considerably antedates that in the nerves, where the fibers. may be preserved by their retinal ganglion cells for several years after complete functional blindness has occurred; 3, our cases serve to illustrate the fact that in the presence of chiasmal pressure of known long duration associated with sharply cut hemianopsias, even when to the ophthalmoscope the nerve shows the pallor of presumed atrophy, there may be no corresponding sharp delineation of the areas of atrophy- in the cross-sections of the nerve; 4, this at first sight wouldt appear to be an inconsistency, but our more accurate peri- metric findings with graded discs show that, after all, the boundaries of the seeing areas are less sharply cut than we had previously supposed, and perhaps correspond after all with the diffuse picture in the nerves." The following four cases are reported in an attempt to show that the microscopic changes, in the optic nerves and chiasm, are sufficient that the type of defect in the visual field can be postulated fairly accurately. These changes seem to be due primarily to a definite groove produced by the arteries of the anterior portion of the circle of Willi's, when the pituitary tumor enlarges and displaces the optic chiasm forward and upward. CASE 1.-Chromophobe adenoma of the pituitary gland, inr which the right anterior cerebral artery affected the optic nerves primarily and produced the defects in the visual field. A farmer, aged forty-five years, came for examination because of loss of vision in the right eye of eighteen months' duration, and failing vision in the left eye during the last month. The visual loss had been progressive. The man did not have other complaints. except that he had had headaches, situated in the frontal region,, during the last ten months. The systolic blood-pressure, in millimeters of mercury, was 132, and the diastolic, 90. The basal metabolic rate was -3 per cent. Roentgenographic examination of the teeth revealed two with periapical infection, and there was mild infection of the tonsils. Roentgenograms of the skull gave evidence of enlargement of the 436 LILLIE: Changes in Optic Nerves and Chiasm sella turcica, with calcification of the pineal gland. Ophthalmic examination demonstrated the ability to perceive light with the right eye and to count fingers with the left. The right was larger than the left and did not react to stimulation by direct light, but reacted normally to consensual light. The left pupil reacted promptly to direct light, but there was no response to consensual light. On ophthalmoscopic examination evidence of simple optic atrophy was found in the right eye, and a normal fundus in the left. The perimetric fields revealed the following: a small area in the nasal portion of the field of the right eye that was sensitive to stimulation by light; in the left eye, concentric contraction to form and color, with a large blind spot and small, absolute central scotoma (fig. 1). The neurologic examination gave negative results. A diagnosis of pituitary tumor was made, and at the operation the surgeon found a brownish-green pituitary tumor that was cystic in nature. The cyst rested on the superior aspect of the optic chiasm, and when the tumor was opened, soft, pulpy, reddish- brown material was obtained. A second similar mass was situated in the sella turcica. After the contents had been removed the capsule collapsed, exposing the optic chiasm and both optic nerves. The left optic nerve was fairly well preserved. The right optic nerve was considerably flattened, but removal of the contents of the cyst relieved the nerve of all pressure. The patient's post-operative course was uneventful until the eighth day, when the concentration of urea in the blood increased to 84 mg. in each 100 c.c., and the blood-pressure dropped to 70 systolic and 40 diastolic. The patient died on the tenth day. At necropsy a frontal decompression was noted, with a slight amount of hemorrhage around the operative site. An attempt was made to remove the brain in the usual way, but a large tumor was found projecting from the sella turcica upward toward the third ventricle. The brain was removed, leaving the optic nerves and chiasm attached to the tumor, and a large cavity was found dis- placing the floor of the third ventricle upward. There was only slight evidence of increased intracranial pressure. On examination of the tumor it was seen that the posterior clinoid processes were eroded, displaced, and partly destroyed. The optic nerves were dislocated upward, sharply angulated on -themselves, and pressed between the tumor mass and the superior margin of the orbital foramen. They were flattened and ribbon- .f.E. as.E lop.

Does not recognise green color o.e. O.D: Simple optic atrophy 0.8: SNggtive Fig. 1.-Case 1. Temporal hemianopsia of right eye and con- centric contraction for form and colors in left eye, associated with absolute central scotoma.

Fig. 2.-Case 1. Definite grooving of the right and left optic nerves, just in front of the optic chiasm, by the right anterior cerebral artery. _".40 ... VIO'-~; Iw m" Op

Fig. 3.-Case 1. Cross-section of the right optic nerve, revealing destruction of the myelin sheaths.

Fig. 4.-Case 1. Cross-section of the left optic nerve, revealing less destruction of the myelin sheaths than in figure 3.

Fig. 5.-Case 1. Cross-section of the optic chiasm, which is flattened, and in which there has been considerable destruction of the mvelin sheaths. LILLIE: Changes in Optic Nerves and Chiasm 437 like on their superior surfaces, and there were deep grooves in the nerves where the right anterior cerebral artery had lain (fig. 2). Grooving of the nerves by the artery had destroyed the substance of the nerves, especially the right one. On the right side also the tumor had projected laterally into the Gasserian ganglion, which was much distended and bulged laterally. On longitudinal section through the tumor it was found to have invaded the sphenoid sinus. A large part of the tumor had been removed surgically and had been replaced by blood-clot. Microscopic section disclosed the fact that the tumor was a chromophobe type of adenoma, such as had been anticipated clinically. Microscopic examination revealed that the right optic nerve was of normal size, that the myelin sheaths had suffered extensive destruction (fig. 3), whereas the myelin sheaths of the left optic nerve, except for two small areas (fig. 4), were well preserved. The optic chiasm was flattened, and examination showed evidence of recent degeneration of the myelin sheaths. One portion was extensively affected, with almost complete disappearance of the myelin (fig. 5). Comment on Case 1.-The grooving of the nerves (fig. 2) in front of the chiasm by the right anterior cerebral artery, as the chiasm was pushed upward against the anterior por- tion of the circle of Willis by the large pituitary tumor, more readily explains the prechiasmal visual defects than would the tumor itself, which was situated more posteriorly. CASE 2.-Chromophobe cystic adenoma of the pituitary gland in which the anterior cerebral artery definitely grooved the optic chiasm to produce the defect of the visual field. This patient, a railroad agent, aged fifty years, came to the clinic complaining of general weakness which had troubled him for the last six months. He had noticed that his work was becom- ing more difficult to him and that he tired more easily. In this period he had lost 20 pounds. For eight years he had noticed diminution of sexual power, and for the year just before his registra- tion at the clinic it had been completely lost. He made no com- plaints referable specifically to vision, although he felt that his sight was failing slightly. The systolic blood-pressure was 100, and the diastolic, 66. The basal metabolic rate was -17 per cent. 438 LILLIE: Changes in Optic Nerves and Chiasm Roentgenograms of the teeth gave evidence that there was peri- apical infection of one of them, and the roentgenogram of the sella turcica disclosed signs of erosion of the posterior clinoid processes and of the base. The ophthalmologic examination showed vision in the right eye to be 6/15, and in the left, 6/10. The external examination gave negative results. The ophthalmoscopic examina- tion disclosed normal discs and fundi. Examination of the peri- metric fields revealed normal perception of form, but there was definite bitemporal hemianopic scotoma for all colors (fig. 6). At operation a mushroom-shaped tumor was found pressing the chiasm from in front and beneath. The tumor was cystic in type, and three grams of fluid were removed with a syringe. Following this the capsule collapsed, so that both optic nerves and chiasm were exposed without trauma and with complete release of all pressure. The capsule was then resected. Following the operation the patient gradually failed and died on the fourth day. At necropsy the brain was removed in the usual way, and it was found that the optic chiasm and floor of the third ventricle were adherent to a tumor that projected from the sella turcica. These were removed, leaving them adherent to the optic nerves. There was no gross abnormality of the brain. The sella turcica was removed, with the cyst intact, and after the chiasm and the floor of the third ventricle had been dissected from the tumor the mass was found to be cystic and filled with recently introduced blood. It was noted that the infundibulum was present and adherent to the floor of the third ventricle. On microscopic examination the tumor was found to be a cystic chromophobe adenoma of the pituitary gland. Under the microscope the myelin sheaths of the left optic nerve were seen to be well preserved throughout practically the entire nerve, except in a small area in the middle, which was about one- sixth of the length of the entire nerve; in this area about one-third of the sheaths were preserved. There was only slight increase in the connective tissue on the median border (fig. 7). Most of the sheaths throughout the right optic nerve, except in a small area at the lower, inner quadrant, were preserved. In cross-section this area was about one-eighth that of the nerve in size, and here about three-fourths of the sheaths were intact (fig. 8). Section through the optic chiasm showed that the myelin sheaths were practically normal, except in the middle area, where there was old destruc- tion, with replacement by connective tissue, and there was also %OLX. ALZ. /

Negtive Fig. 6.-Case 2. Normal fields for form, but bitemporal hemianopsia for colors, and definite bitemporal scotoma involving both maculas.

Fig. 7.-Case 2. Cross-section of left optic nerve, with destruction of the myelin sheaths in the middle area and preservation of the myelin sheaths elsewhere.

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Fig. 8.-Case 2. Cross-section of right optic nerve, with destruction of the myelin sheaths in the lower portion only. ;: .: ... ::: :. : * ." e .

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Fig. 9.-Case 2. Cross-section of the optic chiasm, with destruction of the crossed fibers, but good preservation of the uncrossed fibers.

Fig. 10.-Case 2. Definite grooving of the optic chiasm by the anterior portion of the circle of Willis. LILLIE: Changes in Optic Nerves and Chiasm 439 recent degeneration, lymphocytes, and erythrocytes. In some of the myelin sheaths there was early beading. The uncrossed fibers were not affected (fig. 9). Comment on Case 2.-Again, as in Case 1, the anterior cerebral artery played the important part in producing the defect in the field. In figure 10 this grooving is seen clearly. As the visual loss was recent, when compared with the his- tory of sexual impotence for eight years, one can postulate, with some assurance, that the visual defects were produced only when the tumor became large enough to cause impaction of the optic chiasm against the right anterior cerebral artery, where it forms the anterior portion of the circle of Willis. CASE 3.-Chromophobe adenoma of the pituitary gland which had surrounded the internal carotid arteries and the anterior cere- bral artery, grooving the anterior portion of the optic chiasm. A woman, aged forty-five years, came for examination because of failing vision in both eyes. She had been married at the age of twenty-six years, and her menses had ceased one year later, without pregnancy. Since then she had been well except for occasional headaches in the occipital region. One and a half years before examination she had noticed that her sight was failing in both eyes-more rapidly in the left. The systolic blood-pressure was 110, and the diastolic, 88. The basal metabolic rate was -3 per cent. Urinalysis was negative, except for the presence of a moderate amount of albumin and a few casts. The concentration of urea in the blood was 26 mg. in each 100 c.c. A roentgenogram gave evidence that the sella turcica was enlarged and that the clinoid processes were flattened. On ophthalmologic examination vision in the right eye was found to be 6/20, and in the left, 6/60. The external examination was negative. With the ophthalmoscope, pallor of both discs, without loss of substance, was observed. Examination of the perimetric fields disclosed bitemporal upper quadrant hemianopsia in each eye (fig. 11). The neurologic examination was entirely negative. At operation a large tumor-about 2.5 by 3.5 cm.-presented anterior to the chiasm. The capsule was incised, and degenerated material, of the sort found in cysts, escaped. The capsule collapsed, and the right optic nerve could be seen and seemed to be intact. 440 LILLIE: Changes in Optic Nerves and Chiasm Post-operative nephritis developed, and the concentration of urea in the blood rose to 135 mg. in each 100 c.c. The patient died three days after operation. At necropsy evidence of slight hemorrhage was found at the site of the operation on the brain. The calvarium was removed in the usual manner, and when an attempt was made to remove the brain, a large tumor protruded from the region of the sella turcica, stretching, distorting, and almost destroying the optic nerves, and growing into the floor of, and displacing, the third ventricle. It had also grown into the interpeduncular fossa, and displaced the anterior portion of the pons. When the brain was removed, a large cavity, which had been formed by the tumor, was found in its base. The sella turcica and the surrounding tissues were re- moved, and it was noted that the tumor had invaded all the tissues in the neighborhood, even involving the petrous portion of the temporal bone, growing down into the sphenoid and ethmoid air cells, and partly destroying the optic nerves. As demonstrated on cross-section, the tumor was of the hemorrhagic type, and grossly resembled a partially organized blood-clot. It had com- pletely surrounded the internal carotid arteries on both sides. The Gasserian ganglions were adherent to the tumor, which was re- moved with the sella turcica. On microscopic examination the tumor was found to be a chromophobe adenoma of the pituitary gland. Microscopic examination of the right optic nerve showed a quite diffuse destruction of the myelin sheaths, which were better pre- served at the periphery and in the upper half, whereas approxi- mately one-third of the sheaths in the middle of the nerve and in its lower quadrant were preserved. There was little increase in connective tissue, and no apparent glial proliferation (fig. 12). In the left optic nerve, as in the right, the peripheral fibers were better preserved than the central fibers, and the upper quadrant better preserved than the lower quadrant. There was a slight increase in connective tissue, but no apparent gliosis (fig. 13). There was more extensive destruction of the myelin in the optic chiasm than in the nerves. The fibers which crossed from side to side had undergone beading and destruction, increase in connective tissue, and only slight glial increase. In the periphery of the chiasm, also, there was evidence of destruction, but the uncrossed fibers were in a better state of preservation than those in the central por- tion (fig. 14). E. L/60tpB

SlI1 pallor of discs Fig. 11.-Case 3. Bitemporal upper quadrant hemianopsia for form and colors, with loss of central fixation in left eye.

Fig. 12.-Case 3. Cross-section of the right optic nerve. There has been quite diffuse destruction of the myelin sheaths, but those in the lateral and superior portions are better preserved.

Fig. 13.-Case 3. Cross-section of left optic nerve, with diffuse destruction of the myelin sheaths centrally and preservation of the lateral and peripheral fibers. MUM

Fig. 14.-Case 3. Cross-section of the optic chiasm, with diffuse destruction of the crossed fibers and preservation of the uncrossed fibers.

Fig. 15.-Case 3. The optic chiasm, revealing definite grooving produced by the right anterior cerebral artery.

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fl1or of both discs Fig. 16.-Case 4. Bitemporal hemianopsia for form and colors, with loss of central fixation in left eye. LILLIE: Changes in Optic Nerves and Chiasm 441 Comment on Case 3.-This tumor encased the anterior por- tion of the circle of Willis more completely than the tumor in the previous two cases, and again the grooved chiasm was evident (fig. 15). The visual disturbance was of only one and one-half years' duration, but a metabolic disturbance, cessation of menses, was noted for eighteen years. This, again, would suggest that the optic chiasm was affected only when the tumor was large enough to displace it upward, so that it impinged on the anterior portion of the circle of Willis. CASE 4.-Chromophobe adenoma of the pituitary gland, with complete bitemporal hemianopsia and arterial grooving of the chiasm. The patient was an automobile dealer, aged thirty-three years, who came for examination because of failing temporal vision in each eye. Eight months before he had noticed the failing vision in the left eye and had been given glasses. At this time the maxil- lary antrum was irrigated and pus was found. He was given a saturated solution of potassium iodid internally, but vision did not improve. Six months later the field of vision was charted, and definite bitemporal hemianopsia was discovered. The patient had no other complaints during this period. The systolic blood-pressure was 120, and the diastolic,'80.- The basal metabolic rate was -26 per cent. A roentgenogram gave evidence of destruction of the floor of, and enlargement of, the sella turcica, and erosion of the posterior clinoid processes. The vision in the right eye was 6/7, and in the left, 6/60. The external examination gave negative results. With the ophthalmoscope, pallor of both discs, without loss of substance, was observed. Examination of the perimetric fields revealed bitemporal hemi- for form and colors, with loss of central fixation in the left eye (fig. 16). The neurologic examination gave negative results. At operation a nodular, red, vascular tumor was found, which presented between the optic nerves and partially surrounded the left optic nerve. The capsule was incised, and soft, grayish material was removed. There was a moderate amount of bleeding accompanying this procedure, due to the vascularity of the tumor. When the contents of the capsule had been removed, pressure on both optic nerves was relieved. The patient had a somewhat stormy post-operative course, and died on the fourth day. 442 LILLIE: Changes in Optic Nerves and Chiasm At necropsy blood pigment and a slight amount of blood-clot were present on the surface of the brain and beneath the left frontal lobe. Signs of trauma to the tissue of the brain were not encountered. On removing the brain it was found that a large tumor projected upward from the sella turcica, with distortion, stretching, and compression of the optic nerves and chiasm. The tumor was nodular and irregular, projected upward, and com- pressed the floor of the third ventricle; laterally it compressed the temporal lobes, and posteriorly, the pons. The tumor was separ- ated from these structures and the brain was removed, disclosing a large cavity that was occupied by' the tumor. The growth, along with the sella turcica, was then removed. The vessels of the circle of Willis were apparently normal. The tumor extended laterally on the right side toward the Gasserian ganglion, which it compressed but did not invade. There were no areas of infarction or softening in the brain. Microscopically, the tumor was a chromophobe adenoma of the pituitary gland. In a section of the chiasm the uncrossed fibers were found to be well preserved. In the medial portion of the chiasm, and at its inferior border, there was evidence of considerable recent destruc- tion. The number of blood-vessels was increased, and there was a slight increase in the amount of connective tissue. On the right side the uncrossed fibers were also well preserved. Medialward there was more extensive destruction of the myelin sheaths in the upper border, and the fibers in the middle part were almost com- pletely destroyed. Those few fibers that were preserved showed evidences of active degeneration (fig. 17). In another section, farther back, there was much more extensive destruction of the fibers in the upper half of the chiasm, whereas the lower half was relatively well preserved, even in the middle. Comment on Case 4.-Again, grooving of the chiasm was present, and sufficient and definite changes were present microscopically to explain the defects in the visual fields (fig. 18). SUMMARY Although it would be hazardous to assume that all the ocular pathologic changes encountered in each of the four cases just presented could be due to vascular grooving of the optic chiasm, nevertheless the defects in the visual fields in Fig. 17.-Case 4. Cross-section of optic chiasm, with destruction of the crossed fibers, recent hemorrhage, and good preservation of the uncrossed fibers.

Fig. 18.-Case 4. The optic chiasm, in which is a definite groove produced by the left anterior cere- bral artery. LILLIE: Changes in Optic Nerves and Chiasm 443 each case can be postulated much more accurately from the pathologic arterial groove than from the pituitary tumor This is further substantiated by the fact that the metabolic disturbances were of much longer duration than the visual defects, suggesting that the optic chiasm tolerates consider- able traction and distortion before definite visual defects become manifest to the patient. Inasmuch as there can be little change in the more or less fixed position of the vascular structures at the chiasm, the growth of the tumor gradually displaces the optic chiasm upward until it is in contact with the anterior portion of the circle of Willis. Since the latter cannot be displaced, direct pressure against the chiasm re- sults, producing definite grooving of the optic nerves or chiasm, depending on the previous anatomic relationship of these structures. The arterial grooving of the optic chiasm revealed at necropsy in these four cases substantiates the statement of de Schweinitz that the structures near the optic chiasm must be considered carefully when any definite opimions as to the diagnosis or prognosis of visual defects are attempted. Although it would be impossible, before operation, to pre- dict in which case of pituitary tumor arterial grooving would be found near or at the chiasm, the knowledge that such a condition can be present is sufficient to indicate that a guarded prognosis as to improvement in vision after opera- tion should always be given, even though the tumor is com- pletely removed and the optic chiasm is relieved of all pre- vious pressure and distortion. REFERENCES Cushing and Walker: Brain, March, 1915, xxxvii, p. 341. Fisher: Tr. Ophth. Soc. U. Kingdom, 1911, xxxi, p. 51. Fisher: Proc. Roy. Soc. Med., Six Sections of Neurol. and Ophth., 1913, p. 53. Henschen: Quoted by Cushing and Walker. Hill: Am. J. Ophth., 1923, vi, p. 257. Josefson: Quoted by de Schweinitz. Lillie: J. A. M. A., 1923, lxxxi, p. 1765. 444 MACMILLAN: The Cells in R6nne: Quoted by de Schweinitz. Schaeffer: Anat. Record, 1924, xxviii, p. 243. de Schweinitz: Tr. Ophth. Soc. U. Kingdom, 1923, xliii, p. 12. de Schweinitz and Carpenter: J. A. M. A., 1905, xliv, p. 81. Traquair: Edinburgh M. J., 1913, xi, p. 197. Traquair: Brit. J. Ophth., 1917, i, p. 216; p. 281; p. 337. Traquair: The Doyne memorial lecture, Tr. Ophth. Soc. U. Kingdom, 1923, xliii, p. 480. Walker and Cushing: Arch. Ophth., 1916, xlv, p. 407. Wilbrand and Saenger: Die Neurologie des Auges; ein Handbuch fiur Nerven- und Augenarzte, J. F. Bergmann, Wiesbaden, 1915, vi, p. 292.

ON THE ORIGIN AND DISPOSITION OF THE CELLS IN ENDOPHTHALMITIS* J. A. MACMILLAN, M.D. Montreal, Canada While engaged in a systematic study of infected eyeballs, I observed a tendency on the part of the inflammatory cells to arrange themselves in a distinctive linear manner, and my theory is that the explanation of the development and dis- position of the exudate in endophthalmitis is to be found in part in this linear arrangement of the cells. The phenomenon is not seen in all cases. In severe in- flammations it is hidden by the profusion of cells, or lost through necrosis, while in long-standing inflammations it is obliterated by the organization of the exudates. One must also note that in many cases the sections are of little or no value in a study of endophthalmitis owing to loss of vitre- ous at the moment of sectioning the globes for embedding. Nevertheless, in most cases the lines can be made out in some part of the exudate, and by examining a large series of cases one sees that the arrangement holds not only for every part of the vitreous, but that, by combining the several findings, one gets a composite outline of the exudates in endophthalmitis. A synthetic picture of the cellular distribution in endoph- * Candidate's thesis for membership accepted by the Committee on Theses.