Optic Atrophy Associated with Retinal Disease

Fig. 4.3  Homonymous hemioptic hypoplasia. Eight-year-old girl with history of prematurity and perinatal asphyxia. (a) Ophthalmoscopy showed band atrophy of left optic disc with associated thinning of nasal

nerve fiber layer; (b) Both optic discs were relatively hypoplastic, left one appearing more so. (c) MR scans showed periventricular leukomalacia with preferential involvement of parieto-occipital region bilaterally

Optic Atrophy Associated with Retinal Disease

Primary retinal disorders that involve the nerve fiber layer eventually lead to optic atrophy, and optic atrophy is a late finding in many diffuse degenerative retinal disorders. It is often possible to recognize optic atrophy associated with retinal disease by noting the concurrent retinal findings,

especially marked arteriolar narrowing. An electroretinogram (ERG) is suggested in the case of optic atrophy with marked arteriolar constriction (Fig. 4.4). Retinal disorders associated with optic atrophy include the various congenital retinal dystrophies, tapetoretinal degenerations, neuronal ceroid lipofuscinosis (e.g., Batten disease), infectious/inflammatory retinopathies (e.g., diffuse unilateral subacute neuroretinitis, cytomegalovirus (CMV) retinitis, toxoplasmosis), and central retinal or ophthalmic artery occlusion. It should

be emphasized, however, that optic atrophy is not a typical feature of Leber congenital amaurosis, even in older patients.835 Optic atrophy, especially of the temporal aspect of the disc, may be the sole funduscopic finding in some patients with cone dystrophy. Severe optic disc and adjacent retinal atrophy has been reported in two brothers with incomplete congenital, stationary, night blindness associated with a mutation in the CACNA1F gene.602 Disproportionate involvement of color vision, photophobia, and hemeralopia should increase suspicion for cone dysfunction. Cases of old central retinal artery occlusion may be difficult to distinguish from primary optic atrophy because some cases of central retinal artery occlusion show eventual recanalization of the occluded vasculature after permanent inner retinal damage occurs. The two conditions may be distinguished with electroretinography that shows diminished b waves in cases of arterial occlusion.

Although the ERG is reportedly normal in primary optic atrophy, full-field ERG has recently been demonstrated to show a selective reduction and loss of the photopic negative response (a response originating from the third-order neurons receiving their signals from cones.306 The pattern ERG, which reflects the activity of ganglion cells and their axons, is also abnormal.532,533

Congenital Optic Atrophy Vs. Hypoplasia

Although most prenatal injuries to the developing visual system eventuate in optic nerve hypoplasia, some infants are born with atrophic-appearing discs that are normal in size. Histologically, optic nerve hypoplasia is characterized by a diminution in the number of axons, with normal blood vessels and glial tissue. Optic atrophy is characterized by a

similar histopathology, except that the diameter of the optic nerve may be mildly diminished in some cases and preserved in others. While we have grown accustomed to interpreting optic atrophy as a clinical marker for postnatal visual system injury and hypoplasia as a marker for prenatal injury, the notion that term birth can demarcate these outcomes is simplistic and contrary to clinical experience.374 For example, a congenital hemispheric lesion may be associated with either homonymous hemioptic hypoplasia with no pallor or band atrophy of the optic disc that is contralateral to the side of the lesion (Fig. 4.3).

Why should some prenatal visual system injuries lead to hypoplasia and others lead to pallor? We believe that the timing of injury is the critical determinant of whether the injured optic nerve involutes or becomes pale. As gestation proceeds, the optic nerve may become “hardwired,” so that its size and structural integrity are relatively maintained despite a marked diminution of axons. An analogy may be drawn between this scenario and the brain's ability to mount a glial reaction to injury. This response seems to begin in the late second or early third trimester.51 In the fetal brain, there is limited capacity for glial reaction; therefore, necrotic tissue is completely reabsorbed (liquefaction necrosis), resulting in a porencephalic cyst.51 The mature brain, on the other hand, reacts to injury with significant gliosis; the resulting cavity contains glial septations and an irregular glial wall (multicystic encephalomalacia). Similarly, preservation of the structural integrity of the optic nerve in the face of exaggerated dying out (apostosis) of supernumerary axons may require a certain degree of developmental maturation of the glial system and other supporting structures. This notion is consistent with the observation that optic nerve hypoplasia is often associated with other central nervous system (CNS) malformations that occur early in gestation and are not associated with gliosis (e.g., schizencephaly).