Visual loss

Greater than 90% of patients with the ocular ischemic syndrome relate a history of visual loss in the affected eye(s).⁵ In two-thirds of cases, it occurs over a period of weeks, but it is abrupt in approximately 12%. In this latter group, with sudden visual loss, there is often a cherry-red spot present on funduscopic examination (Fig. 59.1).

Fig. 59.1 Cherry-red spot in the left eye of a 66-year-old man with rubeosis iridis, a 100% ipsilateral common carotid artery obstruction, and a history of rapid visual loss.

Prolonged light recovery

Prolonged recovery following exposure to a bright light has been described in patients with severe carotid artery obstruction.²⁰ Concurrent attenuation of the visual evoked response has also been observed in these cases after light exposure. The phenomenon has been attributed to ischemia of the macular retina. In cases of bilateral, severe carotid artery obstruction, the visual loss after exposure to bright light occurs in both eyes, mimicking occipital lobe ischemia due to vertebrobasilar disease.²¹

Scintillating scotomas

Dissection of the internal carotid artery has been reported to cause scintillating scotomas that resemble a migraine aura.²² While these could theoretically be associated with the classic ocular ischemic syndrome, they have not been observed by the authors.

Amaurosis fugax

A history of amaurosis fugax is elicited in about 10% of ocular ischemic syndrome patients.⁵ Amaurosis fugax, or fleeting loss of vision for seconds to minutes, is thought to most commonly be caused by emboli to the central retinal arterial system, although vasospasm may also play a role.²³ Although the majority of people with amaurosis fugax alone do not have the ocular ischemic syndrome, it can be an indicator of concomitant, ipsilateral carotid artery obstructive disease. About one-third of patients with amaurosis fugax have an ipsilateral carotid artery obstruction of 75% or greater.²⁴ Rarely, it has been associated with a stenosis of the ophthalmic artery.²⁴

Pain

Pain is present in the affected eye or orbital region in about 40% of cases,⁵ and has been referred to as “ocular angina.” Most often, it is described as a dull ache. It can occur secondary to neovascular glaucoma, but in those cases in which the intraocular pressure is normal, the cause may be ischemia to the globe and/or ipsilateral dura.

Visual acuity

The presenting visual acuities of patients with the ocular ischemic syndrome are bimodally distributed, with 43% of affected eyes having vision ranging from 20/20 to 20/50, and 37% having counting fingers or worse vision.²⁵ Absence of light perception is generally not seen early, but can develop in the later stages of the disease, usually secondary to neovascular glaucoma. Among all eyes with the ocular ischemic syndrome after one year of follow-up, including those with and without treatment, approximately 24% remain in the 20/20–20/50 group and 58% have counting fingers vision or worse.

External collaterals

Prominent collateral vessels are occasionally seen on the forehead (Fig. 59.2). These vessels connect the external carotid system on one side of the head to that on the other. These vascular collaterals should not be mistaken for the enlarged tender vessels seen with giant cell arteritis, since temporal artery biopsy may shut down this important source of collateral blood flow to the brain.

Fig. 59.2 Prominent collateral arteries from the right external carotid arterial system to the left external arterial system in a patient with a 100% common left carotid artery stenosis.

Anterior segment changes

Neovascularization of the iris is encountered in approximately two-thirds of eyes with the ocular ischemic syndrome at the time of presentation⁵ (Fig. 59.3). Nevertheless, only slightly over half of these eyes have or develop an increase in intraocular pressure, even if the anterior chamber angle is closed by fibrovascular tissue. Impaired ciliary body perfusion, with a subsequent decrease in aqueous production, probably accounts for this phenomenon.

Fig. 59.3 Gonioscopy of neovascularization of the iris and angle in an eye with the ocular ischemic syndrome. A red arc of fibrovascular tissue is present, closing the anterior chamber angle.

Flare in the anterior chamber is usually present in eyes with rubeosis iridis. An anterior chamber cellular response is seen in almost one-fifth of eyes with the ocular ischemic syndrome,⁵ but it rarely exceeds grade 2⁺, on a 0 to 4⁺ range, as per the Schlaegel classification.²⁶ Keratic precipitates can be present, but are typically small.

In unilateral cases, there is generally little difference between the degree of lens opacification in each eye. As the disease advances, however, cataractous lens changes can develop. In advanced cases, the lens may become mature.

Posterior segment findings

The retinal arteries are usually narrowed and the retinal veins are most often dilated, but not tortuous (Fig. 59.4). The venous dilation may be accompanied by beading, but usually not to the extent seen in eyes with marked preproliferative or proliferative diabetic retinopathy. Dilation of the veins is probably a nonspecific response to the ischemia from the inflow obstruction. Nevertheless, in some eyes both the retinal arteries and veins are narrowed. In contrast, eyes with central retinal vein obstruction usually also have dilated retinal veins, but they are often tortuous. The fact that the ocular ischemic syndrome occurs secondary to impaired inflow, while central retinal vein obstruction is usually associated with compromised outflow resulting from thrombus formation at or near the lamina cribrosa, may account for this difference.²⁷

Fig. 59.4 (A) Narrowed, beaded retinal arteries and dilated, beaded, but not tortuous, retinal veins in an ocular ischemic syndrome eye. (B) Focal narrowing of the retinal arteries (arrows) in the right eye of a 55-year-old man with ocular ischemic syndrome and bilateral internal carotid artery obstructions.

(Panel B reproduced with permission from Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11:239–51.)

Retinal hemorrhages are seen in about 80% of affected eyes. They are most commonly present in the midperiphery, but can also extend into the posterior pole (Fig. 59.5, Fig. 59.6 online). While dot and blot hemorrhages are the most common variant, superficial retinal hemorrhages in the nerve fiber layer are occasionally seen. The hemorrhages probably arise secondary to leakage from the smaller retinal vessels, which have sustained endothelial damage as a result of the ischemia. Similar to the case with diabetic retinopathy, they may also result from the rupture of microaneurysms. In general, the hemorrhages seen with the ocular ischemic syndrome are less numerous than those accompanying central retinal vein obstruction. They are almost never confluent.

Fig. 59.5 (A) Round retinal hemorrhages in the midperiphery of an eye with the ocular ischemic syndrome. (B) Histopathologic correlate of a retinal hemorrhage in an ocular ischemic syndrome eye demonstrates blood throughout the retina (hematoxylin–eosin ×60). (Photograph courtesy of Dr W. Richard Green.) (C) Wide angle photograph demonstrating retinal hemorrhages in the midperiphery in an eye with the ocular ischemic syndrome.

Fig. 59.6 Right fundus of a 35-year-old man with a cherry-red spot, rubeosis iridis, and retinal hemorrhages in the macula. A 95% right internal carotid artery obstruction was present.

Microaneurysms are frequently observed outside the posterior pole, but can be seen in the macular region also. Hyperfluorescence with fluorescein angiography (Fig. 59.7) differentiates these abnormalities from hypofluorescent retinal hemorrhages. Retinal telangiectasia has also been described.²⁸

Fig. 59.7 (A) Ocular ischemic syndrome eye: fluorescein angiogram demonstrating numerous hyperfluorescent microaneurysms in the midperipheral retina. (Reproduced with permission from Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11:239–51.) (B) Histopathologic correlation of a microaneurysm in an eye with the ocular ischemic syndrome discloses that the anomaly traverses the entire retina (periodic-acid Schiff ×60).

(Courtesy of Dr W. Richard Green.)

Posterior segment neovascularization can occur at the optic disc or on the retina. Neovascularization of the disc (Fig. 59.8) is encountered in about 35% of eyes, while neovascularization of the retina is seen in about 8%.⁵ Vitreous hemorrhage arising from traction upon the neovascularization by the vitreous gel has been reported to occur in 4% of eyes with the ocular ischemic syndrome in a retrospective study.⁵ Rarely, the neovascularization can progress to severe preretinal fibrovascular proliferation (Fig. 59.9 online). Neovascularization of the retina (Fig. 59.10 online) is encountered in 8% of eyes with ocular ischemia. It is usually present concomitant with neovascularization of the disc.

Fig. 59.8 (A) Neovascularization of the disc in an eye with the ocular ischemic syndrome. (B) Fluorescein angiogram of the eye in panel (A) reveals marked hyperfluorescence resulting from leakage of dye from new vessels.

(Reproduced with permission from Brown GC, Magargal LE, Simeone FA, et al. Arterial obstruction and ocular neovascularization. Ophthalmology 1982;89:139–46. Copyright © 1982 American Academy of Ophthalmology.)

Fig. 59.9 (A) Fibrovascular proliferation overlying the optic disc and causing retinal traction in an eye with the ocular ischemic syndrome. (Reproduced with permission from Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11:239–51.) (B) Histopathology of an eye with ischemic retinopathy demonstrates a connection of neovascularization of the optic disc on stretch (arrow) between the inferior disc and the superior vitreous gel filled with blood. Presumably, the intravitreal blood occurred as a result of rupture of the thin-walled vessels on stretch (hematoxylin–eosin ×60).

Fig. 59.10 Neovascularization of the retina (arrows) with fluorescein angiography in a nondiabetic person affected by the ocular ischemic syndrome. Retinal capillary nonperfusion (NP) can be seen.

(Reproduced with permission from Brown GC, Magargal LE, Simeone FA, et al. Arterial obstruction and ocular neovascularization. Ophthalmology 1982;89:139–46. Copyright © 1982 American Academy of Ophthalmology.)

A cherry-red spot is seen in approximately 12% of eyes with the ocular ischemic syndrome (see Fig. 59.1).⁵ It can occur secondary to inner layer retinal ischemia from embolic obstruction of the central retinal artery, but probably more often develops when the intraocular pressure exceeds the perfusion pressure within the central retinal artery, particularly in eyes with neovascular glaucoma.

Additional posterior segment signs⁵ include cotton-wool spots (Fig. 59.11 online) in 6% of eyes, spontaneous retinal arterial pulsations in 4% (Fig. 59.12), and cholesterol emboli within the retinal arteries in 2%. In contrast to spontaneous retinal venous pulsations, which are a normal variant and located at the base of the large veins on the optic disc, the arterial pulsations are usually more pronounced, and may extend a disc diameter or more out from the optic disc into the surrounding retina. Anterior ischemic optic neuropathy (Fig. 59.13) has also been reported in ocular ischemic syndrome eyes.^5,29,30 Acquired arteriovenous communications of the retina are rarely seen.³¹

Fig. 59.12 Photographs taken several seconds apart in a fundus affected by the ocular ischemic syndrome. Closure of the retinal arteries can be seen on the right.

(Reproduced with permission from Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11:239–51.)

Fig. 59.13 (A) Pale optic disc resulting from ischemic optic neuropathy in a 67-year-old man with a 100% right internal carotid artery obstruction. Midperipheral retinal hemorrhages and rubeosis iridis were also present. (B) Fluorescein angiogram of the eye in panel (A) at 81 seconds after injection. The nerve head is hypofluorescent.

(Reproduced with permission from Brown GC. Anterior ischemic optic neuropathy occurring in association with carotid artery obstruction. J Clin Neuroophthalmol 1986;6:39–42.)

Fig. 59.11 Cotton-wool spots in the fundus of a man with the ocular ischemic syndrome. Irregularly dilated retinal veins are also evident.

A list of the anterior and posterior segment signs found with the ocular ischemic syndrome is shown in Table 59.1.^1–5,9

Table 59.1 Anterior and posterior segment signs seen in eyes with the ocular ischemic syndrome

(Adapted from Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11:239–51.)

Fluorescein angiography

The intravenous fluorescein angiographic signs⁵ associated with the ocular ischemic syndrome are listed in Table 59.2.

Table 59.2 Fluorescein angiographic signs seen in eyes with the ocular ischemic syndrome

Delayed arm-to-choroid and arm-to-retina circulation times are frequently observed in the ocular ischemic syndrome. However, these measurements may be difficult to assess, since they depend upon whether the dye was injected in the antecubital fossa or hand, and also on the rate of injection. The observation of a well-demarcated, leading edge of fluorescein dye within a retinal artery after an intravenous injection is a distinctly unusual finding. It can be seen in eyes with the ocular ischemic syndrome, secondary to hypoperfusion (Fig. 59.14).

Fig. 59.14 Fluorescein angiogram of an eye with the ocular ischemic syndrome at 38 seconds after injection. A leading edge of the dye (arrow) is present within a retinal artery.

(Reproduced with permission from Brown GC, Magargal LE, Simeone FA, et al. Arterial obstruction and ocular neovascularization. Ophthalmology 1982;89:139–46. Copyright © 1982 American Academy of Ophthalmology.)

Normally, the choroidal filling is completed within 5 seconds after the first appearance of dye. Sixty percent of eyes with the ocular ischemic syndrome demonstrate patchy and/or delayed choroidal filling (Fig. 59.15). In some instances, the filling is delayed for a minute or longer. Although not the most sensitive sign, an abnormality in choroidal filling is the most specific fluorescein angiographic sign in ocular ischemic eyes.

Fig. 59.15 (A) Fluorescein angiogram of an ocular ischemic syndrome eye at 44 seconds after injection shows patchy choroidal filling. A leading edge of dye (arrow) can again be seen within a retinal artery. (Reproduced with permission from Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11:239–51.) (B) Histopathology of an ocular ischemic syndrome retina reveals a paucity of retinal ganglion cells, as well as cells in both the inner nuclear and outer nuclear layers, the latter the cell bodies for the rods and cones. These features occur secondary to panretinal ischemia from both retinal and choroidal hypoperfusion. The retinal pigment epithelial cells appear to be intact, correlating with the clinical picture that retinal pigment epithelial dropout and hyperplasia do not appear to be prominent funduscopic features associated with the ocular ischemic syndrome (hematoxylin–eosin ×60).

(Courtesy of Dr W. Richard Green.)

Prolongation of the retinal arteriovenous transit time is seen in 95% of eyes with the ocular ischemic syndrome (highly sensitive), but can also be seen in eyes with central retinal artery obstruction and central retinal vein obstruction (low specificity). Normally, the major retinal veins in the temporal vascular arcade are completely filled within 10–11 seconds after the first appearance of dye within the corresponding retinal arteries. In extreme cases of the ocular ischemic syndrome, the retinal veins fail to fill throughout the study.