Pathogenesis of optic disc edema in raised intracranial pressure

Abstract

Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure.

Keywords: Brain tumors; Idiopathic intracranial hypertension; Optic disc edema; Raised cerebrospinal fluid pressure.

Conflict of interest statement

The author has no conflict of interest.

Copyright © 2015 Elsevier Ltd. All rights reserved.

Figures

Fig. 1

Sheath of the optic nerve showing its bulbous part behind the eyeball. Reproduced from Hayreh (1965a).

Fig. 2

Longitudinal section of a normal human optic nerve showing the sheath in its different parts. Abbreviations: A= Arachnoid; C = Choroid; D = Dura, OC = Optic canal; ON = Optic nerve; P = Pia; R = Retina; S = Sclera. (Reproduced from Hayreh SS. 1965a)

Fig. 3

Schematic diagram showing various regions of the sheath of the optic nerve (Abbreviations as in figure 2; EB = eyeball). (Reproduced from Hayreh SS. 1965a).

Fig. 4

Longitudinal section of the optic nerve in the rhesus monkey in the region of the optic canal, shows a capillary subarachnoid space (SAS) and fibrous band connecting the optic nerve with the surrounding sheath. (Reproduced from Hayreh SS. 1965a).

Fig. 5

(A) Longitudinal section of the anterior part of the optic nerve of a rabbit, showing distribution of colloidal iron (Blue) in the loose perivascular space around the central retinal artery in the nerve; 20 minutes after its injection in the vitreous. (B) Schematic diagram, showing distribution of colloidol iron (blue) in optic nerve in therabbit. Abbreviations: C=Choroid; CAR=Central artery of the retina; DS =Dural sheath; ON=Optic nerve; R=Retina; S=Sclera (Reproduced from Hayreh SS. 1966).

Fig. 5

(A) Longitudinal section of the anterior part of the optic nerve of a rabbit, showing distribution of colloidal iron (Blue) in the loose perivascular space around the central retinal artery in the nerve; 20 minutes after its injection in the vitreous. (B) Schematic diagram, showing distribution of colloidol iron (blue) in optic nerve in therabbit. Abbreviations: C=Choroid; CAR=Central artery of the retina; DS =Dural sheath; ON=Optic nerve; R=Retina; S=Sclera (Reproduced from Hayreh SS. 1966).

Fig. 6

Schematic representation of blood supply of the optic nerve and retina. Left half shows retinal appearance. (Modified from Hayreh SS. Anatomy and physiology of the optic nerve head. Trans Am Acad Ophthalmol Otolaryngol 1974;78:OP240-54.). Abbreviations: A = arachnoid; C = choroid; CRA = central retinal artery; Pial Col. Br. = Collateralbranches to pia mater; CRV = central retinal vein; CZ = circle of Zinn and Haller; D = dura; LC =lamina cribrosa; OD = optic disc; ON = optic nerve; PCA = posterior ciliary artery; PR =prelaminar region; R = retina; S = sclera; SAS = subarachnoid space.

Fig. 7

Inferior surface of the intraorbital part of the optic nerve (ON), showing the central retinal artery (CRA) and vein (CRV) and their site of penetration into the sheath of the optic nerve in a rhesus monkey. (Reproduced from Hayreh SS 1965b.) Abbreviations: CRA = Central retinal artery; CRV = Central retinal vein; OA = Ophthalmic artery; ON = Optic nerve.

Fig. 8

Fundus photographs (A) immediately after the venous occlusion, and (B) fourteen days later. (C) Shows later on development of optic disc edema when intracranial pressure was raised by inflating a balloon in the temporal region. (Reproduced from Hayreh SS 1965a,.)

Fig. 9

(A) Longitudinal section of the right optic nerve shows the atrophic patches in the lower part of the optic nerve (arrows) around the site of entry of the central retinal vessels, caused by cautery burn. (B,C) Optic discs with raised CSF pressure show optic disc edema in the entire left optic disc (B), but only in the upper half of the right disc, and none in the lower atrophic half (C). (D,E) A section through the upper part of the right optic disc shows edema (D), but lower part of the optic disc in the same section shows optic atrophy (E). (A-E Reproduced from Hayreh SS. l968)

Fig. 9

(A) Longitudinal section of the right optic nerve shows the atrophic patches in the lower part of the optic nerve (arrows) around the site of entry of the central retinal vessels, caused by cautery burn. (B,C) Optic discs with raised CSF pressure show optic disc edema in the entire left optic disc (B), but only in the upper half of the right disc, and none in the lower atrophic half (C). (D,E) A section through the upper part of the right optic disc shows edema (D), but lower part of the optic disc in the same section shows optic atrophy (E). (A-E Reproduced from Hayreh SS. l968)

Fig. 9

(A) Longitudinal section of the right optic nerve shows the atrophic patches in the lower part of the optic nerve (arrows) around the site of entry of the central retinal vessels, caused by cautery burn. (B,C) Optic discs with raised CSF pressure show optic disc edema in the entire left optic disc (B), but only in the upper half of the right disc, and none in the lower atrophic half (C). (D,E) A section through the upper part of the right optic disc shows edema (D), but lower part of the optic disc in the same section shows optic atrophy (E). (A-E Reproduced from Hayreh SS. l968)

Fig. 10

Experimental records of the various pressure responses in a rhesus monkey when the cerebrospinal fluid was acutely raised to different levels. (All pressures in mmHg).) (Reproduced from Hayreh and Edwards 1971a)

Fig. 11

The balloon assembly used in rabbits. (Reproduced from Hayreh SS. l968)

Fig. 12

The balloon with cannula and rubber cap used in rhesus monkeys. (Reproduced from Hayreh SS. 1964b)

Fig. 13

Tip of the cannula (arrow) under the scalp in rhesus monkey with a balloon in the temporal lobe region, as seen from the top. (Reproduce from Hayreh SS. 1965a)

Fig. 14

Schematic diagram showing the balloon and cannula in situ after its introduction. D = Dura. (Reproduced from Hayreh SS. 1964b)

Fig. 15

Radiograph of the head of a rabbit with distended intracranial balloon. (Reproduced from Hayreh SS. 1965a)

Fig. 16

(A) Radiograph (Towne’s views) of an intracerebral balloon on the 80th day of the introduction of the balloon. Note diastasis of skull sutures as a result of the raised intracranial pressure. (Reproduced from Hayreh SS. l968) (B) The cannula and balloon in situ in the brain. (Reproduced from Hayreh SS. 1965a) (C) A horizontal section through a cerebral hemisphere showing the intra-cerebral cavity and the size of the balloon removed from that.

Fig. 16

(A) Radiograph (Towne’s views) of an intracerebral balloon on the 80th day of the introduction of the balloon. Note diastasis of skull sutures as a result of the raised intracranial pressure. (Reproduced from Hayreh SS. l968) (B) The cannula and balloon in situ in the brain. (Reproduced from Hayreh SS. 1965a) (C) A horizontal section through a cerebral hemisphere showing the intra-cerebral cavity and the size of the balloon removed from that.

Fig. 16

(A) Radiograph (Towne’s views) of an intracerebral balloon on the 80th day of the introduction of the balloon. Note diastasis of skull sutures as a result of the raised intracranial pressure. (Reproduced from Hayreh SS. l968) (B) The cannula and balloon in situ in the brain. (Reproduced from Hayreh SS. 1965a) (C) A horizontal section through a cerebral hemisphere showing the intra-cerebral cavity and the size of the balloon removed from that.

Fig. 17

(A) Radiograph (lateral view) of a midline posterior cranial fossa distended balloon. (B) Cerebellum in the same animal, showing the cannula entering the substance of the cerebellum. The balloon is embedded in the substance of the cerebellum. (C) Midline sagittal section of the above cerebellum, showing the cavity of the balloon. (A-C Reproduced from Hayreh SS. 1964b)

Fig. 17

(A) Radiograph (lateral view) of a midline posterior cranial fossa distended balloon. (B) Cerebellum in the same animal, showing the cannula entering the substance of the cerebellum. The balloon is embedded in the substance of the cerebellum. (C) Midline sagittal section of the above cerebellum, showing the cavity of the balloon. (A-C Reproduced from Hayreh SS. 1964b)

Fig. 17

(A) Radiograph (lateral view) of a midline posterior cranial fossa distended balloon. (B) Cerebellum in the same animal, showing the cannula entering the substance of the cerebellum. The balloon is embedded in the substance of the cerebellum. (C) Midline sagittal section of the above cerebellum, showing the cavity of the balloon. (A-C Reproduced from Hayreh SS. 1964b)

Fig. 18

Various sites of entry of the balloons into the cerebral hemisphere, as seen from the superolateral aspect. (Reproduced from Hayreh SS. 1964b)

Fig. 19

Various sites of entry of the balloons into the cerebellum, as seen from the posterior aspect. (Reproduced from Hayreh SS. 1964b)

Fig. 20

(A) Graphic representation of rate of inflation of the intracranial balloon in the occipital region. When the balloon was inflated on second last time (arrow), the animal immediate stopped breathing and went into coma; because on withdrawal of the fluid the animal immediately started to breathe, and became quite normal with no ill-effects. (Reproduced from Hayreh SS. 1965a) (B) Schematic diagram showing pushing down of cerebellum into foramen magnum by a distended occipital lobe balloon. Abbreviation: Tent. Cer. = Tentorium cerebelli.

Fig. 21

Graphic representation of rate of inflation of the balloon in posterior cranial fossa shows levels of the CSF pressure. (Reproduced from Hayreh SS. 1965a)

Fig. 22

Fundus photographs of an eye of a rhesus monkey with temporal lobe balloon. (A) Normal optic disc before insertion of the balloon. (B,C) Fundus photographs with inflation of the balloon – (B) shows moderate optic disc edema, and (C) marked optic disc edema with a disc and peripapillary hemorrhage.

Fig. 23

Fundus photograph (A) and radiograph (B) of a monkey with the distended balloon in the temporal region. (A) Shows marked optic disc edema.

Fig. 24

This shows herniation of the cerebellum through the tentorial notch with the balloon in the posterior cranial fossa. Abbreviation: Tent. Cer. = Tentorium cerebelli.

Fig. 25

Distended lateral ventricle with the balloon in the posterior cranial fossa in Figure 24.

Fig. 26

Fundus photographs (A,B), and late fluorescein angiograms (15 minutes after injection of dye) of left fundus in a rhesus monkey: (A and D) one day and (B and E) seven days after introduction of right temporal fossa balloon. (C) Normal late angiogram before introduction of the balloon. Note progressive increase in severity of ophthalmoscopic and angiographic changes on various occasions. (Reproduced from Hayreh and Hayreh. 1977b)

Fig. 27

Photographs and fluorescein angiograms of left fundus of a rhesus monkey before (A-C), and five days after introduction of left temporal fossa balloon (D-G). Compare ophthalmoscopic and angiographic changes in the eye from its normal (A-C) to edematous (D-G) states. Figures C and G are late angiograms taken 15 minute after injection of dye. (Reproduced from Hayreh and Hayreh. 1977b)

Fig. 28

(A) Fundus photograph of a monkey 22 days after introduction of a left temporal fossa balloon, shows marked optic disc edema. Note presence of peripapillary reflex all around the disc. (B) Fluorescein fundus angiogram of this eye 25 days after introduction of balloon shows masking of optic disc and peripapillary choroidal fluorescence by optic disc edema during retinal arterial phase. (Reproduced from Hayreh and Hayreh 1977b)

Fig. 29

Funds photograph and fluorescein angiograms of left fundus of a rhesus monkey 3½ months after introduction of a right temporal fossa balloon and with 11 ml fluid in it. (A) This shows a wide peripapillary reflex with optic disc edema. (B) This shows dilated capillaries over disc and peripapillary retina, with blurred disc margins during retinal arteriovenous phase. (C) This shows late fluorescein leak in disc 15 minutes after injection of dye. (Reproduced from Hayreh and Hayreh. 1977b)

Fig. 30

Schematic representation of radial peripapillary retinal capillaries. X = Site of foveola (Reproduced from Henkind P. 1967)

Fig. 31

Both eyeballs, optic nerves and optic chiasm show distribution of blue dye in the sheath of the optic nerve. (A) From the superior aspect. (B) From the inferior aspect. (Reproduced from Hayreh SS. 1965a)

Fig. 32

Schematic diagram, showing opened optic nerve sheath. Abbreviations: LR = Lateral rectus; I0= Inferior oblique; IR = Inferior rectus; 0N = Optic nerve; SR= Superior rectus. (Reproduced from Hayreh SS. 1964b)

Fig. 33

(A) Rate of inflation of the balloon and CSF pressure, in a monkey before and after optic nerve sheath fenestration. (Reproduced from Hayreh SS. 1965a) (B) Fundus photographs of both eyes of a rhesus monkey 79 days after insertions of the balloon. The optic nerve sheath was cut opened on the left side 25 days after insertions of the balloon (A). It shows optic disc edema of the right optic disc and normal optic disc on the left side. (Reproduced from Hayreh SS. 1965a)

Fig. 33

(A) Rate of inflation of the balloon and CSF pressure, in a monkey before and after optic nerve sheath fenestration. (Reproduced from Hayreh SS. 1965a) (B) Fundus photographs of both eyes of a rhesus monkey 79 days after insertions of the balloon. The optic nerve sheath was cut opened on the left side 25 days after insertions of the balloon (A). It shows optic disc edema of the right optic disc and normal optic disc on the left side. (Reproduced from Hayreh SS. 1965a)

Fig. 34

(A,B) Longitudinal sections of the optic nerves show anterior part of the optic nerve sheath and its cut region of the sheath. (A) Arrows indicate the two cut edges of the sheath. Abbreviations: A = Arachnoid; D = Dura; N = Ciliary nerve. (B) Shows the cut part of the sheath (black arrow) and the part filled by a loose connective tissue (white arrow).

Fig. 35

Longitudinal sections of optic nerve head in rhesus monkey: (A) Normal, and (B) with swelling of the disc secondary to raised intracranial pressure. (Reproduced from Hayreh SS. 1964b)

Fig. 36

0ptic nerve head of rhesus monkey with optic disc edema secondary to raised intracranial pressure. (A) Note elevation of floor of optic disc. In peripapillary region (arrows), retina is displaced laterally, and axons have vacuolated appearance and abut retinal pigment epithelium (toluidine blue stain, original magnification x 110). (Reproduced from Tso and Hayreh. 1977a) (B) Optic disc edema (toluidine blue stain, original magnification x 100).

Fig. 36

0ptic nerve head of rhesus monkey with optic disc edema secondary to raised intracranial pressure. (A) Note elevation of floor of optic disc. In peripapillary region (arrows), retina is displaced laterally, and axons have vacuolated appearance and abut retinal pigment epithelium (toluidine blue stain, original magnification x 110). (Reproduced from Tso and Hayreh. 1977a) (B) Optic disc edema (toluidine blue stain, original magnification x 100).

Fig. 37

Vacuolated axons (black and white arrows) noted in region of prelaminar and lamina cribrosa regions. Swollen axons (black arrows) are also present in peripapillary region. BM = Bruch's membrane (toluidine blue stain, original magnification x 120). (Reproduced from Tso and Hayreh. 1977a)

Fig. 38

Deeper region of the nerve fiber layer shows accumulation of tracer material in interstitial space (black and white arrows). Horseradish peroxidase-reaction product is entirely confined within its lumen (L). Horseradish peroxidase also infiltrates basement membrane of endothelial cells and pericytes (black arrows) (original magnification x 6,700). (Reproduced from Tso and Hayreh. 1977a)

Fig. 39

Swollen axons (A) in the deeper region of the nerve fiber layer. Neurotubules in axons are disrupted. Some axons in immediate vicinity of swollen axons are of normal size, and their neurotubules and mitochondria appear intact. Glial elements (G) in this region are not swollen (original magnification x 14,600). (Reproduced from Tso and Hayreh. 1977a)

Fig. 40

Some axons (A) in deeper region of the nerve fiber layer are filled with mitochondria and laminated dense bodies. Fibrin deposits (arrows) are observed in interstitial space between axons (original magnification x 7,400). (Reproduced from Tso and Hayreh. 1977a)

Fig. 41

Top: Autoradiograph of optic nerve head of rhesus monkey with optic disc edema secondary to raised intracranial pressure. Eye was enucleated six hours after intravitreous injection of tritiated leucine. Note accumulation of silver grains in ganglion cells of retina (single black arrow), supporting meniscus tissue of Kuhnt (double black arrows), Bergmeister papilla (B), perivascular glial tissue and axonal bundles in region of prelaminar and lamina cribrosa regions (black and white arrows) (paraphenylenediamine, original magnification x 80). Bottom: Prelaminar and lamina cribrosa regions under higher magnification. Note accumulation of silver grains in axonal bundles (arrows). Few grains are present over connective tissue septa separating axonal bundles (paraphenylenediamine, original magnification x 300).

Fig. 42

Autoradiograph of optic nerve head with optic disc edema three days after intravitreous injection of tritiated leucine. Abundant silver grains (arrows) were observed in axonal bundles of entire optic nerve head anterior to retrolaminar myelinated optic nerve (ML) (paraphenylenediamine, original magnification x 60).

Fig. 43

Top: Autoradiograph of optic nerve head with optic disc edema injected with tritiated leucine 12 days before enucleation. Abundant silver grains still present in entire optic nerve head anterior to retrolaminar myelinated optic nerve (ML) (paraphenylenediamine, original magnification x 80). Bottom: Prelaminar and lamina cribrosa regions just anterior to ML under higher magnification. Considerable amount of silver grains still present in axonal bundles (arrows) (paraphenylenediamine, original magnification x 300).

Fig. 44

Grain counts per unit area in different regions of optic nerve head with edema secondary to raised intracranial pressure. Grain counts have been corrected for glial and myelin correction factor. Grain counts for each curve taken from autoradiographic preparation of optic nerve head from eyes enucleated six hours and 1½, 3, 8, and 12 days after intravitreous injection of tritiated leucine. Abbreviations: ALR = anterior part of nerve fiber layer; LC = lamina cribrosa; ML = anterior line of retrolaminar myelinated optic nerve; NFL = Nerve fiber layer; ON = optic nerve; PL = prelaminar region; PLR = posterior part of nerve fiber layer;

Fig. 45

Grain counts per unit area in different regions of the normal optic nerve head. Grain counts have been corrected for glia and myelin correction factor. Grain counts for each curve taken from autoradiograph preparation of optic nerve head from eyes enucleated six hours and 1, 4, and 12 days after injection of tritiated leucine into vitreous cavity. Abbreviations: ALR = anterior part of nerve fiber layer; LC = lamina cribrosa; ML = anterior line of retrolaminar myelinated optic nerve; NFL = Nerve fiber layer; ON = optic nerve; PL = prelaminar region; PLR = posterior part of nerve fiber layer Figs. 46–68: Fundus photographs show three grades of severity of optic disc edema and other fundus changes due to raised intracranial pressure.

Fig. 46. shows moderate degree of optic disc edema, engorged retinal veins and choroidal folds (arrow)

Fig. 47

(A) shows more marked optic disc edema, markedly engorged retinal veins, and dilated capillaries on the optic disc and microaneurysms. (B) Fluorescein fundus angiogram during the arteriovenous phase shows dilated capillaries on the optic disc and in the region of the radial peripapillary and microaneurysms, and fluorescein leakage.

Fig. 48

shows severe degree of optic disc edema, some hemorrhages, markedly engorged retinal veins and choroidal folds in temporal peripapillary region.

Fig. 49

Fundus photograph and fluorescein fundus angiograms of left eye, of a 14-year-old boy with benign intracranial hypertension, taken at first visit. (A) shows severe degree of optic disc edema, some hemorrhages, and markedly engorged retinal veins. (B-E) Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Fig. 49E reproduced from Hayreh SS. 1977a)

Fig. 49

Fundus photograph and fluorescein fundus angiograms of left eye, of a 14-year-old boy with benign intracranial hypertension, taken at first visit. (A) shows severe degree of optic disc edema, some hemorrhages, and markedly engorged retinal veins. (B-E) Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Fig. 49E reproduced from Hayreh SS. 1977a)

Fig. 49

Fundus photograph and fluorescein fundus angiograms of left eye, of a 14-year-old boy with benign intracranial hypertension, taken at first visit. (A) shows severe degree of optic disc edema, some hemorrhages, and markedly engorged retinal veins. (B-E) Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Fig. 49E reproduced from Hayreh SS. 1977a)

Fig. 49

Fundus photograph and fluorescein fundus angiograms of left eye, of a 14-year-old boy with benign intracranial hypertension, taken at first visit. (A) shows severe degree of optic disc edema, some hemorrhages, and markedly engorged retinal veins. (B-E) Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Fig. 49E reproduced from Hayreh SS. 1977a)

Fig. 49

Fundus photograph and fluorescein fundus angiograms of left eye, of a 14-year-old boy with benign intracranial hypertension, taken at first visit. (A) shows severe degree of optic disc edema, some hemorrhages, and markedly engorged retinal veins. (B-E) Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Fig. 49E reproduced from Hayreh SS. 1977a)

Fig. 50

Patient in figure 49 was treated with systemic corticosteroids, which produced marked resolution of optic disc edema in both eyes. Fundus photograph and fluorescein fundus angiograms of left eye are 5½ weeks after initial visit. (A): Fundus photograph shows minimal optic disc edema, with some temporal pallor and retinal folds (arrow). (B-E): Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Reproduced from Hayreh SS. 1977a) Compare severity of fundus and fluorescein fundus angiography in this eye with those in figure 49.

Fig. 50

Patient in figure 49 was treated with systemic corticosteroids, which produced marked resolution of optic disc edema in both eyes. Fundus photograph and fluorescein fundus angiograms of left eye are 5½ weeks after initial visit. (A): Fundus photograph shows minimal optic disc edema, with some temporal pallor and retinal folds (arrow). (B-E): Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Reproduced from Hayreh SS. 1977a) Compare severity of fundus and fluorescein fundus angiography in this eye with those in figure 49.

Fig. 50

Patient in figure 49 was treated with systemic corticosteroids, which produced marked resolution of optic disc edema in both eyes. Fundus photograph and fluorescein fundus angiograms of left eye are 5½ weeks after initial visit. (A): Fundus photograph shows minimal optic disc edema, with some temporal pallor and retinal folds (arrow). (B-E): Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Reproduced from Hayreh SS. 1977a) Compare severity of fundus and fluorescein fundus angiography in this eye with those in figure 49.

Fig. 50

Patient in figure 49 was treated with systemic corticosteroids, which produced marked resolution of optic disc edema in both eyes. Fundus photograph and fluorescein fundus angiograms of left eye are 5½ weeks after initial visit. (A): Fundus photograph shows minimal optic disc edema, with some temporal pallor and retinal folds (arrow). (B-E): Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Reproduced from Hayreh SS. 1977a) Compare severity of fundus and fluorescein fundus angiography in this eye with those in figure 49.

Fig. 50

Patient in figure 49 was treated with systemic corticosteroids, which produced marked resolution of optic disc edema in both eyes. Fundus photograph and fluorescein fundus angiograms of left eye are 5½ weeks after initial visit. (A): Fundus photograph shows minimal optic disc edema, with some temporal pallor and retinal folds (arrow). (B-E): Fluorescein fundus angiograms during the early retinal arterial (B), late retinal arterial (C), retinal arteriovenous (D), and late (E) phases. (Reproduced from Hayreh SS. 1977a) Compare severity of fundus and fluorescein fundus angiography in this eye with those in figure 49.

Fig. 51

Right eye of a patient with idiopathic intracranial hypertension shows marked optic disc pallor, with mild optic disc edema, peripapillary retina hemorrhages and peripapillary atrophy.

Fig. 52

Fluorescence of the optic discs of rhesus monkey. (A) Right optic disc one hour after intravenous injection of 1 ml 25% fluorescein shows optic disc fluorescence, with fluorescent outline of the retinal vessels. (B-D) Right eye is after injection of 1 ml 25% fluorescein solution into cisterna magna, after release of same amount of cerebrospinal fluid. B through D show progressive intense fluorescence of the optic disc ½, 1, and 1½ hours, respectively after the injection. At 3½ hours after injection, both optic discs were intensely fluorescent and no fundus details were visible. (Reproduced from Hayreh SS. 1977a)

Fig. 53

Fluorescence photomicrographs of frozen longitudinal histologic sections of optic nerve after injection of fluorescein in cisterna magna, as figure 52. (A) Through center of intraorbital part of optic nerve containing central retinal vessels. (B) Through optic nerve head (on left) and retrolaminar optic nerve (on right). (Reproduced from Hayreh SS. 1977a)

Fig. 54

Right eye of a patient with idiopathic intracranial hypertension, shows (A) severe optic disc edema and cilioretinal artery occlusion. (B) There is a centrocecal scotoma corresponding to the distribution of the occluded cilioretinal artery.

Fig. 55

Inferior surface of cerebral hemispheres and midbrain of a rhesus monkey with left temporal lobe balloon in situ (white arrow), shows herniated part of left parahippocampal gyrus surrounded temporally by compression mark (black arrow) produced by free edge of tentorium cerebelli, and compressed, displaced, and distorted midbrain. (Reproduced from Hayreh SS. 1977b)