Figure 11-23 Retinal neovascularization. The new blood vessels have broken through the internal limiting membrane.
In some cases of retinal ischemia, neovascularization of the retina and the vitreous may occur, most commonly in diabetes and central retinal vein occlusion. Retinal neovascularization generally consists of the growth of new vessels on the vitreous side of the ILM (Fig 11-23); only rarely does neovascularization occur within the retina itself. Hemorrhage may develop from retinal neovascularization as the associated vitreous exerts traction on the fragile new vessels. Retinal neovascularization should be distinguished from retinal collaterals and arteriovenous shunts, which represent dilation and increased flow in existing retinal vessels.
Specific Ischemic Retinal Disorders
Central and branch retinal artery and vein occlusions
Central retinal artery occlusions (CRAO) result from localized arteriosclerotic changes, an embolic event, and, in rare instances, vasculitis (as in temporal arteritis). As the retina becomes ischemic, it swells and loses its transparency. This swelling is best appreciated clinically and histologically in the posterior pole, where the NFL and the ganglion cell layer are the thickest (Fig 11-24). Because the ganglion cell layer and the NFL are thickest in the macula but absent in the fovea, the normal color of the choroid shows through in the fovea and produces a cherry-red spot, ophthalmoscopically suggesting CRAO. The retinal swelling eventually clears and leaves the classic histologic picture of inner ischemic atrophy (see Fig 11-13). Scarring and neovascularization following CRAO are rare.
Figure 11-24 Acute central retinal artery occlusion. Histologically, necrosis occurs in the inner retina (asterisk) corresponding to the retinal whitening observed by ophthalmoscopic examination. Note the pyknotic nuclei (arrow) in the inner aspect of the
inner nuclear layer. (Courtesy of Robert H. Rosa, Jr, MD.)
Branch retinal artery occlusion (BRAO) is usually the result of emboli that lodge at the bifurcation of a retinal arteriole. Hollenhorst plaques, which are cholesterol emboli within retinal arterioles, seldom occlude the vessel. Emboli may be the first or most important clue to a significant systemic disorder such as carotid vascular disease (Hollenhorst plaques), cardiac valvular disease (calcific emboli), or thromboembolism (platelet-fibrin emboli).
The histology of the acute phase of BRAO is characterized by swelling of the inner retinal layers with the death of all nuclei. As the edema resolves, a classic picture emerges of inner ischemic atrophy in the distribution of the retina supplied by the occluded arteriole. The NFL, the ganglion cell layer, the inner plexiform layer, and the inner nuclear layer are affected (see Fig 11-13). Arteriolar occlusions result in infarcts with complete postnecrotic atrophy of the affected layers.
Central retinal vein occlusion (CRVO) occurs at the level of the lamina cribrosa. The pathophysiology of CRVO is the same as that of hemiretinal vein occlusion but different from that of branch retinal vein occlusion (see the following discussion). CRVOs develop as a result of structural changes in the central retinal artery and the lamina cribrosa that lead to compression of the central retinal vein. This compression creates turbulent flow in the vein and predisposes to thrombosis. These
structural changes occur in arteriosclerosis, hypertension, diabetes, and glaucoma. Papillophlebitis refers to a condition in which the clinical features of CRVO are present, but there is no history of vascular disease. In this variant of CRVO, which typically occurs in younger patients (<50 years), inflammation of the retinal vessels at the optic disc has been shown to be a causative factor in retinal vein occlusion.
CRVO is recognized clinically by the presence of retinal hemorrhages in all 4 quadrants. Usually, prominent edema of the optic nerve head occurs, along with dilation of the retinal veins, variable numbers of cotton-wool spots, and macular edema. CRVO occurs in 2 forms: a milder, perfused type and a more severe, nonperfused type.
Nonperfused CRVO was defined in the Central Vein Occlusion Study (CVOS) as a CRVO in which greater than 10 disc areas showed nonperfusion on fluorescein angiography. Nonperfused CRVOs typically have extensive retinal edema and hemorrhage. Marked venular dilation and a variable number of cotton-wool spots are found.
Acute ischemic CRVO is characterized histologically by marked retinal edema; focal retinal necrosis; and subretinal, intraretinal, and preretinal hemorrhage. With long-standing CRVO, glial cells respond to the insult by replication and intracellular deposition of filaments (gliosis). The hemorrhage, hemosiderosis, disorganization of the retinal architecture, and gliosis seen in vein occlusions distinguish the final histologic picture from that seen in CRAO (Fig 11-25). Numerous microaneurysms are present in the retinal capillaries following CRVO, and acellular capillary beds are present to a variable degree. With time, dilated collateral vessels develop at the optic nerve head. Neovascularization of the iris is common following ischemic CRVO.
Branch retinal vein occlusion (BRVO) is a disorder in which occlusion of a tributary retinal vein occurs at the site of an arteriovenous crossing. At the crossing of a branch retinal artery and vein, the 2 vessels share a common adventitial sheath. With arteriosclerotic changes in the arteriole, the retinal venule may become compressed, leading to turbulent flow, which predisposes to thrombosis. This condition is more common in patients with arteriosclerosis and hypertension.
BRVO leads to retinal hemorrhages and cotton-wool spots. Because BRVO does not always result in total inner retinal ischemia and death of all tissue, neovascularization is unlikely unless the ischemia is extensive (>5 disc diameters). Findings in eyes with permanent vision loss from BRVO include CME, retinal nonperfusion, pigmentary macular disturbance, macular edema with hard lipid exudates, subretinal fibrosis, and epiretinal membrane formation.
The histologic picture of BRVO resembles that seen in CRVO but is localized to the area of the retina in the distribution of the occluded vein. Inner ischemic retinal atrophy is a characteristic late histologic finding in both retinal arterial and venous occlusions (see Fig 11-13). Numerous microaneurysms and dilated collateral vessels may be present. Acellular retinal capillaries are present to a variable degree, correlating with retinal capillary nonperfusion on fluorescein angiography.
Baseline and early natural history report. The Central Vein Occlusion Study. Arch Ophthalmol. 1993;111(8):1087–1095.
