Optic Nerve Aplasia Curtis E.

Margo, MD; Latif M. Hamed, MD; Ervin Fang, MD; William

\s=b\ Optic nerve aplasia is a rare congenital defect invariably associated with other ocular or systemic disorders. We examined a 3-year-old girl with monocular microphthalmos who had optic nerve aplasia on histopathologic examination of the eye after enucleation. Magnetic resonance imaging verified the presence of unilateral optic nerve aplasia, and demonstrated hemichiasmal hypoplasia on the affected side and bilateral optic tracts. The visually evoked cortical response revealed increased signals over the occipital cortex ipsilateral to the aplastic nerve, suggesting misdirection of axons from the temporal retina of the normal eye. The visual pathway in unilateral optic nerve aplasia may assume a primitive form of neuronal organization characterized by an increase in contralateral retinogeniculostriate projection.

(Arch Ophthalmol. 1992;110:1610-1613)

malfor/^ptic ^ mation. Some of the studies ad¬ dressing aplasia actually described pa¬ tients with optic nerve hypoplasia at a time when the latter entity was not clearly recognized.1"3 For aplasia to ex¬ ist, there must be complete absence of the optic nerve (including the optic disc), retinal ganglion and nerve fiber layers, and optic nerve vessels. We describe a patient with unilateral microphthalmos who had unilateral op¬ tic nerve aplasia diagnosed on histo¬ pathologic examination of the enucle¬ ated globe. Magnetic resonance imaging (MRI) provided further verification of the aplasia as well as documentation of nerve

aplasia is

a rare

Accepted for publication July 9, 1992. From the Department of Ophthalmology, University of Florida College of Medicine, Gainesville. Reprints not available.


Dawson, PhD

the effect of the malformation on the re¬ mainder of the anterior visual pathway. REPORT OF A CASE A

3-year-old girl was referred with a his¬

tory of microphthalmos of the right eye since

birth. She was the product of a full-term pregnancy and normal delivery. She was hospitalized for 3 days after birth for jaun¬ dice, but since then met all her developmen¬ tal milestones. The family medical history was unremarkable. Visual acuity was no light perception OD and 20/50 Snellen equivalent OS with the Teller acuity cards. Severe microphthalmia in the right eye was noted in association with marked ptosis, enophthalmos, and profound developmental delay of the bony orbit. The horizontal corneal diameter measured 5.0 mm OD and 11 mm OS. A dense lenticular opacity of the right eye precluded visualiza¬ tion of the fundus. The anterior segment and fundus of the left eye were normal. The left eye displayed a left-beating nystagmus, more marked in abduction and essentially absent in adduction. Cycloplegic refraction revealed + 5.25 spherical error in the left eye. B-scan echography revealed a small right eye with soft tissue filling most of the vitreal

cavity. Safety spectacles with a hyperopic correc¬ tion for the left eye were prescribed. Fol¬ lowing discussion with the patient's parents,

enucleation of the right eye was decided on improve the appearance and stimulate growth of the surrounding tissue. Each of the six extraocular muscles was intraoperatively identified. When the globe was removed, external examination re¬ vealed no evidence of an optic nerve or its sheath (see "Pathologic Findings" below). Nine weeks after enucleation MRI of the head and orbits was performed. The left or¬ bit, optic nerve, and portions of the optic chiasm related to the nerve on the left side were normal. The optic nerve and sheath complex were not visible within the right orbit or anywhere along the usual course of the nerve (Fig 1). The chiasm was present but abnormal. The right side was elevated to

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hypoplastic (Fig 2). Although inconspic¬ coronal sections, the optic tracts were each approximately half the diameter of the left optic nerve on sagittal views (Fig and

uous on

were no detectable differences in the lateral geniculate bodies and no other associated brain anomalies.

3). There


The right eye measured 13X13X 12 mm and had a small, oval cornea measuring 5x8 mm. The optic nerve and its sheath could not be identified. The globe was opened vertically and a 9-mm central section was submitted for processing. Every 10th slide from the serially sectioned globe was stained with hemotoxylin-eosin and examined

microscopically. The corneal epithelium showed microcystic edema. Bowman's layer was

intact. There was minimal stromal cleft ing. Descemet's membrane was of nor¬ mal thickness, but endothelial cells were reduced in number. The angle was open. Patchy vascularization of the an¬ terior iris surface was present. The lens was thick and showed focal calcification and liquefactive degeneration. An an¬ terior subcapsular fibrous plaque and posterior synechiae were present. Fi¬ brovascular tissue was noted in the posterior chamber arising from the vas¬ cularized vitreal tissue. The vitreal cavity was filled with gliotic, disorganized retina (Fig 4). A small amount of condensed, vascularized vit¬ reous was present anteriorly. The reti¬ nal pigment epithelium and choroid were largely absent (colobomatous mal¬ formation) in the inferior hemisphere. Gliotic tissue replaced the posterior uveal tract in these areas. There was no evidence of retinal dysplasia. Several foci of hyperplastic retinal pigment ep-

Fig 3.—Left, Magnetic resonance image of the left sagittal section shows a normal left optic it approaches the chiasm (arrow). The left optic tract is present and approximately half the diameter of the ipsilateral optic nerve. Right, Magnetic resonance image of the right sagittal section shows the right optic tract posterior to the chiasm (arrow) but no right optic nerve. nerve as

Fig 1.—Magnetic resonance image of coro¬ nal sections of the orbital, intracanalicular, and intracranial optic nerve. The anatomical right side is shown on the left. The absence of the optic nerve in the right posterior orbit is evident when compared with the normal op¬ tic nerve in the left posterior orbit (top, arrow). At the level of the optic foramen, the left optic nerve is present (center, arrow), but the nerve is not found on the right. The left intracranial optic nerve is present (bottom, arrow), butthe right is not.

Fig 2.—Magnetic resonance ¡mage of the coronal section of the chiasm shows that the right side (arrow) is tilted and smaller than the left side. ithelium and dystrophic calcium were present in the gliotic retina. Similar, but smaller defects in the choroid and reti¬ nal pigment epithelium were noted su¬ periorly. There was no optic disc or op¬ tic nerve. The gliotic tissue was in direct contact with sclera in the region in which the optic nerve normally enters

the eye. The sclera was uniformly thick and the scierai canal absent. A small rudimentary tag of dura mater was attached to the sclera adja¬ cent to the posterior ciliary nerves and vessels (Fig 4). The posterior ciliary ar¬ teries were enlarged as they traversed the sclera anterior to the equator. After these vessels penetrated the choroid, they formed retinal-vitreal communica¬ tions supplying the anterior vitreous and posterior segment.

hemisphere signals showed a generally triphasic waveform beginning with the smaller positive potential at about 80 milliseconds, and were similar to the classic signal components described by Jeffreys and Axford.4



Visual stimulation was provided by a rectangular computer-graphics display of a 50/50 grating of approximately 85%

The pathogenesis of optic nerve apla¬ sia remains speculative. Possibilities include defective formation of the em¬ bryonal fissure, failure of the mesen¬ chymal anläge of the hyaloid system to enter the embryonal fissure, or primary agenesis of the retinal ganglion cells. Whether optic nerve aplasia and hy¬ poplasia are fundamentally different pathogenetically is controversial, and some authorities consider these condi¬ tions to be on the same spectrum of de¬

contrast, which subtended 20x25 de¬ grees of visual angle. Integrated lumi¬ nance of the grating display was ap¬ proximately 1.2 log foot-lamberts in a surrounding of approximately 1.8 log foot-lamberts. The dark and light grat¬ ings counterphased at a rate of 1.5 Hz. Synchronized cortical responses were amplified by 10000, recorded by com¬ puter, and averaged in two channels. The active electrodes were 3 cm to the left and to the right of midline over the occipital pole (Fig 5). Both active elec¬ trodes were referenced to the same site over the right mastoid. Signals from the right hemisphere electrode and from the left hemisphere electrode are shown in Fig 5. Responses were also recorded following diffuse Ganzfeld light stimu¬ lation (not shown) with approximately the same lateralization. Responses over the right hemisphere produced by a 50-minute arc grating and an 18-minute arc grating showed

pronounced negativity at approxi¬ mately 120 milliseconds and pro¬ nounced positivity at approximately 300 milliseconds. Signals over the left

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hemisphere elicited by both grating

sizes were not significantly different from the control recording or noise level. The control recordings were made with an opaque block between the patient's eye and the display. The right


development." Agenesis of each of the components of the anterior visual pathway, including the eyeball (anophthalmos), optic nerve, optic chiasm, and optic tract, has been described.613 Optic nerve aplasia may

be unilateral or bilateral. The unilateral variety tends to be more benign, most commonly associated with ipsilateral microphthalmos in an otherwise normal patient.6,7 Bilateral optic nerve aplasia tends to occur in association with more serious and widespread congenital


The appearance of the optic chiasm and optic tracts in our patient was interesting and is the first report, to our knowledge, describing their existence with MRI in optic nerve aplasia. To

Fig 4.—Histologie section of the enucleated right eye shows a mass of gliotic retina (R) filling the vitreous cavity. The retinal pigment epithelium ends abruptly (solid arrow) in the region in which the optic disc should be. The choroid to the right is replaced with gliotic tissue (asterisk). A small residual tag of dura (open arrow) is attached to the outer sclera. A focal chorioretinal adhesion is noted in the center of the field (hematoxylin-eosin, original magnification x28).

better understand the implications of the findings, a review of the develop¬ ment of the chiasm is needed. The optic nerve fibers reach the embryological anläge of the chiasm between the fourth and fifth weeks of development, pro¬ ducing an identifiable chiasm by the seventh week as the fibers decussate. However, uncrossed fibers do not ap¬ pear until the 11th week. If optic nerve aplasia in our patient was due to primary failure of formation of the nerve axons, this implies that axonal input from only one side suffices to produce decussation as well as for¬ mation of the chiasm and the optic tract.14 Causative factors in the development of isolated aplasia of the optic nerve are virtually unknown. Hoff et al15 de¬ scribed a patient with unilateral anophthalmos with optic nerve aplasia associ¬ ated with a congenital giant suprasellar aneurysm. The remaining optic nerve was identified at craniotomy as passing directly posteriorly to form the optic tract as a single cord, without any evi¬ dence of a chiasm. It was postulated that the chiasm and optic nerves in this patient formed initially and then degen¬ erated retrograde.15 Patients with severe bilateral optic nerve hypoplasia have demonstrated diffuse chiasmal hypoplasia on MRI.16 Patients with unilateral or asymmetri¬ cal optic nerve hypoplasia have shown variable abnormalities of the chiasm on MRI, including diffuse chiasmal thin¬ ning, attenuation limited to the side of the hypoplastic disc, and focal absence of the lateral third of the chiasm corre¬

sponding to an ipsilateral, severely hy¬ poplastic nerve.17,18 This latter finding is similar to that in our patient, perhaps reaffirming the view that hypoplasia and aplasia may not be fundamentally different, but rather exist on the same spectrum of defective development.5 Failure of one optic nerve to develop

does not appear to interfere with some axonal decussation or with formation of the contralateral optic tract. The visually evoked cortical response demonstrated increased signals over the occipital cortex ipsilateral to the aplastic optic nerve. This finding was unexpected. The asymmetric, visually evoked potentials indicate misdirection of axons of the temporal retina with greater than normal contralateral

projection. Fig 5.—Visually evoked cortical response. Event-related left and right hemisphere responses primary visual cortex. Electrodes recorded two differential signals with a common mas-

over the

toid reference. Active electrodes were 3 cm lateral to midline. Stimuli were 50/50 square-wave gratings, spatially counterphased at 1.5 Hz. Grating sizes (right side) subtended two angles of 50 and 18 minutes. The control (C) recordings were taken with view of the display blocked.

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A similar pattern of misrouting has been described in human albinos and most mammals with albinism.19,20 This anatomical anomaly has been shown by Apkarian et al21 to have a clearly de¬ fined electrophysiologic consequence in humans. In albinos, the temporal field



routed to the contralateral

primary visual cortex via the lateral geniculate nucleus. Electrical signals recorded from electrodes placed later¬ ally on both hemispheres indicated se¬ lective responding over the right pri¬

mary visual cortex when the left eye stimulated monocularly and over the left primary visual cortex when the right eye was stimulated monocularly. Although this visually evoked potential profile has been considered pathognomonic to albinism,22 it is nearly identi¬ cal to the pattern reported in our pa¬ tient with unilateral optic nerve was


Our findings suggest that although gross axonal decussation can occur in unilateral optic nerve aplasia, normal retrochiasmal development requires the interaction of two optic nerves. The retrochiasmal pathway in persons with unilateral optic nerve aplasia may rep¬ resent an atavistic form of neuronal

organization.23 This study


Research to Prevent Blind¬ Institute

Ine, New York, NY, and National Eye grant 5R01 EY04460 (Dr Dawson). ness

1. Scheie

HG, Adler FH. Aplasia of the optic Arch Ophthalmol. 1941;26:61-70. 2. Smith HE. Aplasia of the optic nerve: report of three cases. Am J Ophthalmol. 1954;37:498-504. 3. LaFranchi SH. Sexual precocity with hypothalamic hypopituitarism. AJDC. 1979;133:739-742. 4. Jeffreys DA, Axford JG. Source location of pattern specific components of human visualevoked potentials, I: component of striate cortical origin. Exp Brain Res. 1972;16:1-19. 5. Hotchkiss ML, Green WR. Optic nerve aplasia and hypoplasia. J Pediatr Ophthalmol Strabisnerve.



6. Weiter JJ, McLean IW, Zimmerman LE. Aplasia of the optic nerve and disk. Am J Ophthalmol. 1977;83:569-576. 7. Storm RL, PeBenito R. Bilateral optic nerve aplasia associated with hydroencephaly. Ann Ophthalmol. 1984;16:988-992. 8. Ginsberg J, Bove KE, Cuesta MG. Aplasia of the optic nerve with aniridia. Ann Ophthalmol.


9. Awan KJ. Ganglionic neuroretinal aplasia and hypoplasia: aplasia and hypoplasia of optic nerve.


Ophthalmol. 1976;8:1193-1202. M, Rorke LB, Allman MI. Bilateral optic system aplasia with relatively normal eyes. Arch Ophthalmol. 1978;96:97-101. 10. Yanoff

11. Little LE, Whitmore PV, Wells TW Jr. Aplasia of the optic nerve. J Pediatr Ophthalmol.

supported in part by an unrestricted

departmental grant from


1976;13:84-88. 12. Barry DR. Aplasia of the optic nerves. Int Ophthalmol. 1985;7:235-242. 13. Margo CE, Hamed LM, McCarty J. Congenital optic tract syndrome. Arch Ophthalmol. 1991;


109:1120-1122. 14. Rogalski T. The visual paths in a case of unilateral anophthalmia with special reference to the problem of crossed and uncrossed visual fibers. J Anat (Lond). 1946;80:153-159. 15. HoffJ, Winestock D, Hoyt WF. Giant suprasellar aneurysm associated with optic stalk agenesis and unilateral anophthalmos. J Neurosurg.


16. Brodsky MC, Glasier CM, Pollock SC, Angtuago EJC. Optic nerve hypoplasia: identification by magnetic resonance imaging. Arch Ophthalmol. 1990;108:1562-1567. 17. Slamovits TL, Kimball GP, Frieberg TB, Cortin HD. Bilateral optic disc colobomas with orbital cysts and hypoplastic optic nerves and chiasm. J Clin Neuro-ophthalmol. 1989;9:172-177. 18. Lambert SR, Hoyt CS, Narahara MH. Optic nerve hypoplasia. Surv Ophthalmol. 1987;32:1-9. 19. Creel D, Witkop CJ, King RA. Asymmetric visually evoked potential in human albinos: evidence for visual system anomalies. Invest Ophthalmol. 1974;13:430-440. 20. Guillery RW, Okoro AN, Witkop CJ Jr. Ab-

normal visual pathway in the brain of an albino. Brain. 1975;96:373-377. 21. Apkarian P, Reits D, Spekreijse H. A decisive electrophysiological test for human albinism. Electroencaphalogr Clin Neurophysiol. 1983;55: 513-531. 22. Apkarian P. Methodology of testing for albinism with visual-evoked cortical potentials. In: Heckenlively J, Arden G, eds. Principles and Practice of Clinical Electrophysiology of Vision. St Louis, Mo: Mosby-Year Book; 1991:433. 23. Guillery RW, Kass JH. A study of normal and congenitally abnormal retinogeniculate projections in cats. J Comp Neurol. 1971;143:73-100.

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Optic nerve aplasia.

Optic nerve aplasia is a rare congenital defect invariably associated with other ocular or systemic disorders. We examined a 3-year-old girl with mono...
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