Histopathology of Retinal Diseases

Age-related macular degeneration (AMD). Drusen, the hallmark of AMD, are extracellular deposits located beneath the retinal pigment epithelium (RPE) on the inner surface of Bruch’s membrane (arrowhead). Note the intact RPE and photoreceptor cell layer over the drusen (A). A drusenoid detachment of the RPE is present (B). Also seen are focal areas of hypertrophy of the RPE (arrows), loss of the photoreceptor inner and outer segments, and attenuation of the outer nuclear layer over the retinal pigment epithelial detachment.

Exudative age-related macular degeneration (AMD). In selected cases, choroidal neovascularization (CNV) might be amenable to surgical extraction. Most of the membranes exhibit two components histologically: subretinal (asterisk) and sub-retinal pigment epithelial (double asterisk). In this surgically excised membrane, photoreceptor outer segments (open arrows) focally line the inner surface of the membrane. Basal laminar deposit (BLD)—a histologic marker for AMD—is a periodic acid-Schiff-positive granular material beneath the retinal pigment epithelium (arrowhead). The role

of inflammation in AMD is unknown; however, multinucleated giant cells (arrows) have been reported in association with CNV and BLD in AMD.

Nonexudative age-related macular degeneration (AMD). Geographic atrophy is observed in more advanced nonexudative AMD. The macular region is identified by the thick ganglion cell layer (>2 to 3 cells thick) (asterisk). Note the abrupt transition (arrow) between normal retina (right of arrow) and geographic atrophy (left of arrow). Geographic atrophy is characterized histologically by loss of the photoreceptor cell layer, retinal pigment epithelium, and choriocapillaris (open arrow). Note the intact choriocapillaris (arrowhead) beneath the normal retina.

Exudative age-related macular degeneration. Occult choroidal neovascularization (CNV) (between arrowhead and arrow) is typically located beneath the retinal pigment epithelium (RPE) and within Bruch’s membrane. The arrowhead identifies basal laminar deposit, which rests on the RPE basement membrane and localizes the inner surface of Bruch’s membrane. The arrow identifies the outer surface of Bruch’s membrane. Note the disorganization of the outer retina and RPE and loss

of the photoreceptors overlying the CNV.

Exudative age-related macular degeneration. The macular region is identified by the thickness of its ganglion cell layer (>2 to 3 cells thick) (between brackets). Note the cystoid macular edema with cystic spaces in the outer plexiform and, to a lesser extent, inner nuclear layers (asterisks). A disciform macular scar (between arrows) is present and composed of subretinal fibrovascular tissue, occasional chronic inflammatory cells, and hyperplastic retinal pigment epithelium (arrowhead). The bottom arrow identifies the outer aspect of Bruch’s membrane.

Cystoid macular edema (CME). Cystoid macular edema is a common finding in various vascular and inflammatory conditions of the eye. Proteinaceous material originating from incompetent or hyperpermeable retinal capillaries accumulates in the outer plexiform layer (called Henle’s layer in the macular region), forming cysts (asterisks) that may extend into the inner nuclear layer. Aggregates of lipid-laden macrophages (arrows, inset) may be observed and correspond clinically to hard exudates.

Idiopathic polypoidal choroidal vasculopathy (IPCV). Pathologic studies indicate that choroidal

neovascularization (CNV) is a common finding in IPCV. In one study, cavernous vascular channels (asterisks) and CNV were present between the retinal pigment epithelium (arrowhead) and the outer aspect of Bruch’s membrane (arrow) in the peripapillary region. On serial stepped sections, the cavernous vascular channels were contiguous with branches of the short ciliary arteries. Note the dense subretinal blood (B), which

is characteristic of this disease.

Epiretinal membrane (ERM). The cellular constituents of idiopathic ERMs typically include fibrous astrocytes and fibrocytes (often with myoblastic differentiation, which accounts for the contractile properties of the membrane) and occasionally Müller cells. In association with a retinal break or detachment, retinal pigment epithelium may also be observed in an ERM. Note the contraction features of the internal limiting membrane caused by this thin, hypocellular ERM (arrows). Clinically, retinal striae and cellophane maculopathy would be apparent on ophthalmoscopy in such a case.

Branch retinal vein occlusion (BRVO). In a remote BRVO, the thrombus (between arrows) becomes organized (fibrotic) and often exhibits recanalization (arrowhead). Note the thickened, hyalinized wall (asterisk) of the adjacent arteriole, indicating the systemic risk factor of hypertension in BRVO.

Central retinal artery occlusion (CRAO). In acute CRAO, ischemic infarction of the inner two thirds of the retina occurs. Histopathologic changes include edema or thickening of the inner retina and coagulative necrosis, accounting for the retinal whitening seen clinically. Note the fragmented or pyknotic nuclei (arrow) in the inner nuclear layer. The photoreceptor cell layer (including the outer nuclear layer and the inner and outer segments) is intact, as its nutrients and oxygen

are supplied by diffusion from the choroid.

Central retinal artery occlusion (CRAO). The majority of emboli to the retina are cholesterol emboli or Hollenhorst plaques. Platelet-fibrin thrombi are often observed in CRAO in association with calcific or cholesterol emboli. Note the central retinal artery (A) and vein (V) in the region of the lamina cribrosa (between brackets). An organized thrombus is present in the central retinal artery (asterisk). At higher magnification (inset), recanalization (arrow) of the central retinal artery is apparent.

Inner ischemic retinal atrophy and hypertensive retinal and choroidal vascular changes. Inner ischemic retinal atrophy is a common histopathologic finding after central and branch retinal artery and vein occlusions. It is characterized by marked thinning of the inner retina, with loss of the nerve fiber, ganglion cell, and inner plexiform layers, and the inner one third to two thirds of the inner nuclear layer. Note the intact outer plexiform layer (asterisk) and the intact subjacent photoreceptors (arrowheads). Note also the difference between the relative thickness of the inner and outer nuclear layers. Hypertensive changes (arteriolar sclerosis—thickening of the blood vessel wall) are present in the inner retina (arrows) and choroid (open arrow).

Cotton wool spot. This nerve fiber layer infarct is characterized by fusiform thickening of the nerve fiber layer of the retina (between arrows) and cytoid bodies (arrowheads). Cytoid bodies are swollen ganglion cell axons with a nucleoid (eosinophilic aggregate of cytoplasmic organelles) and stagnant axoplasmic flow.

Retinal telangiectasis. Irregular retinal capillary dilation and variable thickening of the blood vessel walls characterize this retinal vascular disorder (inset). Note the numerous variably sized blood vessels in the inner retina in this case. In one area, a dilated blood vessel extends into the outer plexiform layer (arrowhead).

Intraretinal hemorrhages. Flame-shaped hemorrhages correlate pathologically with blood in the nerve fiber layer (arrows). Dot and blot hemorrhages are localized to inner and outer nuclear layers and the outer plexiform layer (between arrowheads). These types of hemorrhages are nonspecific and are seen in various ocular conditions including diabetic, hypertensive, and radiation retinopathies, shaken baby syndrome, and retinopathy of blood dyscrasias.

Retinal telangiectasis (Coats’ disease). In advanced stages of this vascular anomaly, extensive intraand subretinal exudation can occur. Note the numerous lipid-laden macrophages (arrows) in all layers of the retina and in the subretinal eosinophilic proteinaceous exudate.

Diabetic retinopathy. An early change in the fundus of diabetic patients is the formation of microaneurysms (arrows), which are outpouchings of the retinal capillaries with basement membrane thickening. Note the focal laser scar (open arrow) characterized by thinning of the retina, gliosis, loss of the normal lamellar architecture, and retinal pigment epithelial hyperplasia. Hypertensive changes (arteriolar sclerosis—thickening of the blood vessel wall) are present in the choroid (asterisks).

Neovascularization of the optic disc (NVD) and retina (NVE). Retinal and optic disc neovascularization occurs as a pathologic response to retinal ischemia and may be associated with several systemic and localized ocular diseases—including diabetic retinopathy, sickle cell retinopathy, and central and branch retinal vein occlusion. This eye with diabetic retinopathy exhibits NVD (between arrowheads), NVE (arrow), cystoid edema (asterisks), and vitreous hemorrhage.

Neovascularization of the optic disc. Condensed vitreous (asterisk) with blood vessels (arrows) is present overlying the optic disc and internal limiting membrane (ILM) (arrowhead) of the peripapillary retina. Note the apparent contraction and folds in the ILM.

Neovascularization of the retina. Retinal neovascularization is usually contiguous with the venous circulation of the retina. Small defects in the internal limiting membrane (between arrows) are observed

at the site of origin. Note the condensed vitreous (arrowhead), which serves as a matrix or scaffold for the proliferation of the new vessels at the vitreoretinal interface. A few cysts are present in the outer plexiform layer (asterisk).

Retinopathy of prematurity (ROP). Temporal dragging of the optic disc and macula may occur in ROP secondary to contraction of neovascularization of the retina near the equator. Note the displacement of the optic disc (asterisk) onto the temporal retinal pigment epithelium (RPE) and choroid. The nasal peripapillary retina (R)

is displaced temporally and rests on the optic nerve. Nasal and temporal peripapillary scleral crescents (brackets) are present with absence of the RPE in these areas.

Retinopathy of prematurity (ROP). Intraretinal microvascular abnormalities (IRMA) and neovascularization of the retina (NVE) may be observed in ROP. A form of intraretinal neovascularization, IRMA is also seen in diabetic retinopathy. Note the ghost-like vessels (arrows) within the nerve fiber layer consistent with IRMA and the condensed epiretinal vitreous with similar vessels (arrowhead) representing NVE.