Experimental retinal vascular occlusion. II. A clinico-pathologic correlative study of simultaneous occlusion of central retinal vein and artery.

After experimentally occluding the central retinal vein and artery simultaneously at their point of entry into the optic nerve, acute retinal necrosis occurred, but not hemorrhagic retinopathy. In the retinal vasculature, stagnation of blood flow and thrombosis with subsequent recanalization was noted. The necrosis was extensive in the inner retinal layers but focal in the outer retinal layers. The internal limiting membrane was detached and disrupted in every case. Following the post-edematous stage, numerous micro and macroretinal cysts appeared. The peripheral retina showed much less ischemic changes. A clinico-pathologic correlation was made.

Experimental retinal vascular occlusion. III. An ultrastructural study of simultaneous occlusion of central retinal vein and artery.

The retinal changes following the simultaneous occlusion of retinal vessels were examined at an ultrastructural level. The preservation of endothelial cells that prevented leakage of blood and horseradish peroxidase tracer material in the surrounding retinal tissues explained the lack of hemorrhages observed clinically. Mueller cell death resulted in severe structural disorganization of the retina, with disruption of the inner limiting membrane, involvement of the outer retinal layers, and fleurette formation. The retinal macrocysts were derived from ischemic infarction.

Hemi-central retinal vein occulsion. Pathogenesis, clinical features, and natural history.

A two-trunked central retinal vein (CRV) in the anterior part of the optic nerve may persist as a congenital abnormality in a certain proportion of humans. One of the two trunks, like the CRV, may get occulded in the optic nerve to produce hemi-CRV occulsion (hemi-CRVO). It is shown that hemi-CRVO is a distinct entity, clincially and pathogenetically closely related to CRVO, and unrelated to branch retinal vein occlusion because of fundamental differences between the two. Hemi-CRVO clinically presents as either venous stasis retinopathy (VSR) or as hemorrhagic retinopathy (HR), usually involving one half of the retina, although ocassionally it may involve one third to two thirds of the retina. The clinical features of VSR and HR caused by hemi-CRVO are identical to those caused by CRVO. The primary object of this article is to identity hemi-CRVO, a not uncommon condition, and to describe its main clinical features.

Experimental injury of the optic nerve with optic disc swelling.

An ultrastructural study utilizing horseradish peroxidase was performed to determine the mechanism and consequences of leakage of vascular protein following injury of the optic nerve. Unilateral optic nerve injuries were produced in four rhesus monkeys by making a cautery lesion on the retrobulbar portion of the optic nerve. Optic disc changes were followed with stereo fundus photography and fluorescein angiography. Three to 14 days after injury horseradish peroxidase was given intravenously and the tissue was prepared for electron microscopy, including serial sections of selected tissue blocks. Fundus photography and fluorescein angiography showed edema of the optic disc in two animals. There was leakage of horseradish peroxidase into the optic nerve head from the optic nerve lesion and the peripapillary choriocapillaris. Although the pathway of horseradish peroxidase leakage in the injured optic nerve was not entirely clear, serial sections indicated intraendothelial channels as one possible route. Alterations of the optic nerve head were confined to the axon segments anterior to the injury, and included aggregation of mitochondria, disruption of neurotubules, and swelling. These findings suggest that optic nerve injury produces damming of axoplasmic flow and that swelling of the optic nerve head is the result of axon enlargement.

Experimental retinal vascular occlusion. I. Pathogenesis of central retinal vein occlusion.

In 45 eyes of rhesus monkeys, five types of central retinal vascular occlusion were produced by lateral orbitotomy: group 1, central retinal vein occlusion (CRVO) alone; group 2, CRVO with simultaneous central retinal artery (CRA) occlusion; group 3, CRVO with transient clamping of the CRA for either 2 to 2 1/2 hours (group 3A) or 6 to 7 1/2 hours (group 3B); and group 4, CRVO with segmental retinal ischemia. The eyes were examined by fundus photography and fluorescein angiography for up to nine months. Group 1 developed venous stasis retinopathy (VSR) and group 3B hemorrhagic retinopathy (HR). In group 4 the ischemic and nonischemic segments of the retina developed segmental HR and VSR, respectively. Groups 2 and 3A developed neither VSR nor HR. Retinal capillary obliteration occurred in groups 2 and 3B and in the ischemic part of group 4, starting one to three weeks after the occlusion and progressing thereafter. These studies indicate that clinically co-called CRVO consists of two distinct entities: VSR and HR, with retinal ischemia playing an important role in the production of HR. On the basis of the present and other available information, the pathogenesis of CRVO was concluded to be multifactorial.

Methyl alcohol poisoning. IV. Alterations of the morphological findings of the retina and optic nerve.

The ocular morphological findings of three methyl alcohol-intoxicated rhesus monkeys with optic disc swelling was investigated with light and electron microscopy in conjunction with intravascular horse radish peroxidase. Alterations observed in the optic nerve head were confined to the axons and consisted of swelling and clustering of the mitochondria, disruption of the neurotubules, the formation of vesicles, and enlargement of the axon segments in the prelaminar region. Swelling of the oligodendroglial cytoplasm in contact with the axons and of the astrocytes was seen in the retrolaminar optic nerve and the intraorbital optic nerve. Alterations were not observed in the retina. It is hypothesized that the alterations in the axons are the result of disrupted axoplasmic flow. Possible mechanisms relating methyl alcohol intoxication to disruption of axoplasmic flow are discussed.

Methyl alcohol poisoning III. Ocular toxicity.

The ocular toxicity of methyl alcohol has been investigated in six rhesus monkeys. All the animals developed fundus changes within 43 to 171 hours after its ingestion. The only fundus lesion seen was optic disc edema and associated changes, usually of a marked degree. Fluorescein fundus angiography confirmed the findings. The retinal and choroidal circulations, including the retinal capillary bed, were normal. Ophthalmoscopically and angiographically, optic disc edema in methyl alcohol poisoning was indistinguishable from that seen in raised intracranial pressure, except that no increased intracranial pressure was observed. It is postulated that optic disc edema in methyl alcohol poisoning is due to an axoplasmic flow stasis.

Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey.

Rhesus monkeys were intoxicated with methyl alcohol, using an initial dose of 2 gm/kg and subsequent doses were administered in order to maintain an attenuated and prolonged state of intoxication. Arterial blood samples were drawn for methyl alcohol, formate, PO2, PCO2, and pH, which were monitored periodically throughout the course of the experiment. With the use of these procedures monkeys developed metabolic acidosis with the accumulation of formic acid in the blood and a corresponding decrease in blood bicarbonate. These animals served as models, which allowed for ocular evaluation for early signs related to methyl alcohol poisoning. A mechanism to explain toxicity is proposed and discussed.

Optic disc edema in raised intracranial pressure. I. Evolution and resolution.

Progressively growing intracranial space-taking lesions were simulated in 32 rhesus monkeys by balloons introduced into the subarachnoid space of the temporal region. Optic disc edema (ODE) first appeared at the lower pole, then the upper pole, then the nasal part, and last the temporal part of the disc; severity of edema generally followed sult, most severe at the lower pole (P less than .005). Fluorescein fundus angiography showed that swelling of the optic disc preceded the vascular changes associated with ODE. Raised intracranial pressure for 24 hours, or less, could cause ODE. The atrophic part of the optic disc did not develop ODE. The studies indicate that swelling of the optic disc is the first sign of raised intracranial pressure and is due to swelling of the nerve fibers in the optic disc; the various associated vascular changes are secondary.

Optic disc edema in raised intracranial pressure. II. Early detection with fluorescein fundus angiography and stereoscopic color photography.

Optic disc edema (ODE) due to chronic intracranial hypertension was produced experimentally in rhesus monkeys. Serial studies of fundus changes at frequent intervals, by routine ophthalmoscopy, steroscopic color photography, and fluorescein angiography, revealed that swelling of the optic disc was the first sign of ODE. Other early signs were striation of nerve fibers on the optic disc margins and peripapillary retina, blurring of the disc margins, hyperemia of the disc and capillary dilation, hemorrhages, and other retinal vascular changes; these usually appeared in that sequence. The classically described signs of early ODE were almost always absent. A normal fluorescein fundus angiogram during the incipient stage did not rule out ODE. Stereoscopic color fundus photography was the most sensitive means of detecting early ODE. Fluorescein angiography did not show changes till edema was of a mild to moderate degree; routine ophthalmoscopy was the least reliable method.