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Clinicopathologic Reports, Case Reports, and Small Case Series
May 2002

Acquired Retinal Myelination in Neurofibromatosis 1

Arch Ophthalmol. 2002;120(5):659-661. doi:

Myelination of the anterior visual pathways begins centrally at the lateral geniculate body and is completed at term. This process normally terminates at the lamina cribrosa, but it occasionally may extend into and beyond the peripapillary retinal nerve fiber layer. Congenital retinal myelination is not uncommon, occurring in 0.3% to 0.6% of the population as an isolated developmental anomaly, or rarely as part of a generalized disorder, such as the Goltz-Gorlin syndrome, or the syndrome of anisometropia high myopia, and amblyopia.1 Although recent evidence suggests that the retinal myelination may progress in such cases,2 acquired retinal myelination is exceptionally rare.3

We describe 2 cases in which myelinated retinal nerve fibers appeared in children with neurofibromatosis 1 (NF1) and optic nerve glioma. In both cases, spontaneous improvement in visual function preceded the retinal myelination.

Report of Cases
Case 1

An 8-year-old boy was referred to us with reduced vision and optic disc swelling in the right eye. There was a maternal family history of NF1, and he had cutaneous features of NF1 and Lisch nodules. The right eye was proptosed, with optic disc edema, opticociliary shunt vessels, and a relative afferent pupil defect (RAPD) (Figure 1). Corrected visual acuity was reduced to 20/80 OD, and a magnetic resonance imaging (MRI) scan confirmed the presence of an optic nerve glioma. Visual field testing, which was reliably repeatable in this child, showed an enlarged blind spot and peripheral constriction on the right side. No treatment was initiated, and annual follow-up was arranged.

Figure 1.
Swollen optic disc with opticociliary
shunts (case 1).

Swollen optic disc with opticociliary shunts (case 1).

Within a year, visual acuity 20/30 OD, the RAPD resolved, and the visual field enlarged. The disc edema resolved, and the shunt vessels disappeared.

Four years after the initial visit, examination showed myelinated nerve fibers adjacent to the right optic disc (Figure 2). Visual acuity was stable at 20/30 OD, and the MRI findings were unchanged. The retinal features have remained unchanged for 4 years.

Figure 2.
Pale optic disc with myelinated
nerve fibers (case 1).

Pale optic disc with myelinated nerve fibers (case 1).

Case 2

An 8-year-old boy was referred with reduced vision and a pale left optic disc. He had features of segmental NF1, with café-au-lait spots on the left chest wall and the imaging features of a left optic nerve glioma extending to the optic nerve head on MRI scan (Figure 3). Corrected visual acuities were 20/15 OD and 20/30 OS with left optic atrophy. A full systemic evaluation was performed, but no treatment was initiated. Visual acuity remained stable during the next 2 years, and then gradually improved to 20/20 OS. Five years after the initial visit, he had developed segmental myelination of the peripapillary retinal nerve fibers in the left eye (Figure 4). These findings have remained unchanged for 2 years.

Figure 3.
Magnetic resonance imaging scan
showing optic nerve glioma (case 2).

Magnetic resonance imaging scan showing optic nerve glioma (case 2).

Figure 4.
Acquired myelination adjacent
to optic disc (case 2).

Acquired myelination adjacent to optic disc (case 2).

Comment

Myelin is deposited in the central nervous system by oligodendrocytes. The 2 major glial cells of the central nervous system (the type 2 astrocyte and the oligodendrocyte) are derived from stem cells known as oligodendrocyte precursor cells, which actively produce myelin prenatally. Myelination ceases at birth as the oligodendrocytes mature into adult type cells and the biochemical stimulus for myelination (notably platelet-derived growth factor) is withdrawn.4

The mechanisms of termination of the myelination at the lamina cribrosa are not clearly understood. This process is important, as opaque nerve fibers would affect vision. Regulatory proteoglycans have been shown to determine where the retinal ganglion cell body ends and the axon begins. This ganglion-axon junction is at the level of the lamina cribrosa in the human optic nerve. Myelination is limited to the axon, and therefore does not extend beyond the lamina cribrosa.5

Certain animals such as rabbits lack a lamina cribrosa, and myelinated retinal nerve fibers are a normal feature of their eyes. The lamina cribrosa may therefore act as a physical barrier to keep oligodendrocytes out of the retina.

There is experimental evidence of a physical barrier at the ocular end of the rat optic nerve, and a similar mechanism has been postulated in humans.6

Myelination could occur postnatally if the barrier were disrupted and/or the oligodendrocytes were stimulated. The barrier may be directly distorted by the tumor as in case 2, or disrupted by disc edema in case 1. Previously described cases of acquired retinal myelination have occurred following resolution of papilloedema2 or associated with optic disc drusen,3 where there would be disruption of the lamina cribrosa.

Stem cell proliferation in NF1 occurs due to local inactivation of a tumor supressor gene.7 In the anterior visual pathway, this process produces optic glioma—characteristically an indolent tumour. It is recognized that visual function in optic gliomas can improve spontaneously, with improvement in the scan appearance.8 The improvement in vision in this case was most likely not due to tumor regression, but to axonal remyelination by oligodendrocytes locally reactivated by the same process that triggered the optic glioma. If the lamina cribrosa is also disrupted, remyelination could extend into the retina, with the process stopping, as the stem cell proliferation is self-limiting.4

These 2 cases, therefore, provide an insight into the complex dynamic of focal tissue growth disorders in NF1. Tumor growth is not exponential, but modified by focal repair mechanisms.

Corresponding author and reprints: John S. Elston, BSc, MD, Radcliffe Infirmary, Oxford Eye Hospital, Woodstock Road, Oxford OX2 6HE, England (e-mail: Mary.Spearman@orh.anglox.nhs.uk).

References
1.
Lee  MSGonzalez  C Unilateral peripapillary myelinated retinal nerve fibers associated with strabismus, amblyopia, and myopia. Am J Ophthalmol. 1998;126853Article
2.
Ali  BHLogani  SKozlov  KLArnold  ACBateman  B Progression of retinal nerve fiber myelination in childhood. Am J Ophthalmol. 1994;118515- 517.
3.
Jean-Louis  GKatz  BJDigre  KBWarner  JECreger  DD Acquired and progressive retinal nerve fiber layer myelination in an adolescent. Am J Ophthalmol. 2000;130361- 362. Article
4.
Tang  DGTokumoto  YMRaff  MC Long-term culture of purified postnatal oligodendrocyte precursor cells: evidence for an intrinsic maturation program that plays out over months. J Cell Biol. 2000;148971- 984. Article
5.
Perry  VHLund  RD Evidence that the lamina cribrosa prevents intraretinal myelination of retinal ganglion cell axons. J Neurocytol. 1990;19265- 272. Article
6.
French-Constant  CMiller  RHBurne  JFRaff  MC Evidence that migratory oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells are kept out of the rat retina by a barrier at the eye-end of the optic nerve. J Neurocytol. 1988;1713- 25Article
7.
Lau  NFeldkamp  MMRoncari  L  et al.  Loss of neurofibromin is associated with activation of RAS/MAPK and PI3-K/AKT signaling in a neurofibromatosis 1 astrocytoma. J Neuropathol Exp Neurol. 2000;59759- 767.
8.
Parsa  CFHoyt  CSLesser  RL  et al.  Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging. Arch Ophthalmol. 2001;119516- 529. Article
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