Myelination in the central nervous system proceeds in a proximal-to-distal fashion (from the cell toward its axon), whereas myelination of the optic nerve proceeds in a distal-to-proximal direction (from the axon in the lateral geniculate body toward the retinal ganglion cells).1 Normal myelination of the optic nerve typically starts at the lateral geniculate body at 5 months of gestation, progresses to the optic tract at 7 months of gestation, continues anteriorly from the optic chiasm to the optic nerve from the eighth month of gestation, and terminates at the lamina cribrosa at approximately 3 months after birth.2,3 Oligodendrocytes are the cells responsible for myelination in the central nervous system, including the optic nerve.4 Normally, oligodendrocytes are not found anterior to the lamina cribrosa and the retinal nerve fiber layer is not myelinated.
Straatsma et al.2 first described the prevalence of myelination of the retinal nerve fiber layer (MNFL) in 0.98% of eyes, affecting males and females equally. Bilateral involvement is less common and is seen in 7.7%.2 Most frequently, it is located in the superior peripapillary region.2 Most cases of MNFL are considered congenital and sporadic, whereas acquired MNFL is rare.5–7 Several reports described MNFL in children with structural anomalies, including optic glioma in neurofibromatosis type 1,5,6 optic nerve sheath fenestration following chronic papilledema secondary to arterial venous malformation,4 bilateral optic nerve drusen,7 and Arnold–Chiari malformation and hydrocephalus.1
We describe two children with bilateral acquired MNFL associated with presumed idiopathic intracranial hypertension. The research was approved by the Hadassah-Hebrew University Medical Center Institutional Review Board committee.
A 6-month-old boy presented to the emergency department with developmental delay and increasing head circumference. He was born 42 weeks after gestation with a birth weight of 3,195 grams, following a normal pregnancy and delivery. On examination of the fundus, early papilledema was noted as mild blurring of both optic nerve borders, without hemorrhages or exudates. Brain magnetic resonance imaging was normal except for possible mild expansion of the third ventricle, with normal lateral and fourth ventricles. Lumbar puncture demonstrated opening pressure of 29 cmH2O, with normal cerebrospinal fluid biochemistry and cytology composition. He was diagnosed as having presumed idiopathic intracranial hypertension and weight-adjusted oral acetazolamide treatment was initiated. During the following months, his head circumference age-adjusted percentile began to drop toward the 50th percentile. He continued to fail the developmental milestones and was also diagnosed as having a pervasive developmental disorder. One year later, repeated lumbar puncture was normal (opening pressure 20 cmH2O) and optic nerves had returned to normal. During tapering of oral acetazolamide, he presented with worsening of neurological symptoms with an increased tendency to fall.
A mild increase in NFL thickness was noted on optical coherence tomography imaging. Combined with the clinical neurological deterioration, this resulted in the recommendation for reinstitution of oral acetazolamide, leading to rapid clinical improvement. Nine months later, the optic nerves appeared with a small whitish area in the superior-nasal aspect of the disc bilaterally (Figure 1). This finding was presumed to be MNFL, and had not been observed on any of the previous examinations. During the next 2 years, there was a continuous expansion of the MNFL area (Figure 1). On a recent follow-up visit, 3 years following the diagnosis of idiopathic intracranial hypertension, his ophthalmic examination was essentially normal apart from large areas of MNFL next to the optic nerves in both eyes (Figure 1).
Fundus imaging of patient 1 (Topcon TRC-50DX, non-mydriatic fundus camera, Tokyo, Japan).
A healthy 7-year-old boy presented to the emergency department with a new onset headache, without vomiting. Fundus examination demonstrated moderate blurring of both optic nerve borders, without hemorrhages or exudates. Brain magnetic resonance imaging was interpreted as normal. Lumbar puncture demonstrated opening pressure of 33 cmH2O. The cerebrospinal fluid had a normal biochemistry and cytology composition. Based on these findings, a presumptive diagnosis of idiopathic intracranial hypertension was made and weight-adjusted oral acetazolamide treatment was initiated. Eight months following his diagnosis, his headaches resolved completely. Fundus examination revealed normal-looking optic nerves with a new whitish area next to the left optic nerve compatible with MNFL (Figure 2). Oral acetazolamide tapering was initiated.
Fundus imaging of patient 2 (Topcon TRC-50DX, non-mydriatic fundus camera, Tokyo, Japan).
Two months later, the boy returned to the emergency department with recurrent headache. Fundus examination revealed bilateral moderately blurred optic nerve borders, without hemorrhage or exudates. Although repeated magnetic resonance imaging of the brain was interpreted as normal, lumbar puncture examination showed an opening pressure of 33 cmH2O. Oral acetazolamide treatment was reinstituted. After this episode, repeated fundus examinations demonstrated normal optic nerves, with progression of the MNFL in the left eye. Eighteen months following his presentation, his comprehensive ophthalmological examination was normal. However, the MNFL in the left eye had expanded, and a new presumed MNFL had developed next to his right optic disc (Figure 2). Acetazolamide was discontinued, and he remained asymptomatic.
To our knowledge, this is the first report that clinically and consecutively documents by high-definition fundus imaging both the onset and the progression of acquired MNFL following idiopathic intracranial hypertension in children.
These children were both presumably diagnosed as having idiopathic intracranial hypertension due to the appearance of optic disc edema on presentation, elevated intracranial pressure of unknown etiology on lumbar puncture, normal cerebrospinal fluid biochemistry and cytology composition, and normal magnetic resonance imaging. Both children responded favorably to oral acetazolamide.
The pathogenesis of the MNFL is idiopathic. Berliner8 postulated in 1931 that the structure of the lamina cribrosa itself inhibits further myelination of the retinal nerve fiber, implying that abnormalities of the cribriform plate (congenital or acquired) may result in failure to prevent the entry of oligodendrocyte lineage cells from the optic nerve.
It is uncertain whether the appearance of MNFL in the setting of idiopathic intracranial hypertension may present a prognostic sign. On one hand, chronic papilledema may damage the lamina cribrosa and result in development of MNFL.9 On the other hand, chronic papilledema may result in ganglion cell axon loss, with regression of the MNFL.10
Although the significance of MNFL in the setting of idiopathic intracranial hypertension is still unclear, as clinicians we should be aware of the possible acquired and progressive form of MNFL in children, and suggest future studies correlating visual fields and optical coherence tomography of the optic disc to this finding. Because both children were treated by oral acetazolamide, additional studies should also address the possible correlation of this treatment with MNFL onset and progression.
- Ali BH, Logani S, Kozlov KL, Arnold AC, Bateman B. Progression of retinal nerve fiber myelination in childhood. Am J Ophthalmol. 1994;118:515–517. doi:10.1016/S0002-9394(14)75805-2 [CrossRef]7943132
- Straatsma BR, Foos RY, Heckenlively JR, Taylor GN. Myelinated retinal nerve fibers. Am J Ophthalmol. 1981;91:25–38. doi:10.1016/0002-9394(81)90345-7 [CrossRef]7234927
- Ruttum MS, Poll J. Unilateral retinal nerve fiber myelination with contralateral amblyopia. Arch Ophthalmol. 2006;124:128–130. doi:10.1001/archopht.124.1.128 [CrossRef]16401798
- Aaby AA, Kushner BJ. Acquired and progressive myelinated nerve fibers. Arch Ophthalmol. 1985;103:542–544. doi:10.1001/archopht.1985.01050040084024 [CrossRef]3985835
- Teixeira F, Fonseca AC, Pinto F. Acquired and progressive myelinated retinal nerve fibers in neurofibromatosis type 1 [published online ahead of print Feb 14, 2019]. J AAPOS. https://doi.org/10.1016/j.jaapos.2019.01.012
- Parulekar MV, Elston JS. Acquired retinal myelination in neurofibromatosis 1. Arch Ophthalmol. 2002;120:659–655.12003622
- Jean-Louis G, Katz BJ, Digre KB, Warner JE, Creger DD. Acquired and progressive retinal nerve fiber layer myelination in an adolescent. Am J Ophthalmol. 2000;130:361–362. doi:10.1016/S0002-9394(00)00550-X [CrossRef]11020421
- Berliner ML. Cytologic studies on the retina: I. Normal coexistence of oligodendroglia and myelinated nerve fibers. Arch Ophthalmol. 1931;6:740–751. doi:10.1001/archopht.1931.00820070769009 [CrossRef]
- Elbaz H, Peto T, Butsch C, et al. Prevalence and associations of myelinated retinal nerve fibers: results from the Population-Based Gutenberg Health Study. Retina. 2016;36:2364–2370. doi:10.1097/IAE.0000000000001093 [CrossRef]27258670
- Shah M, Park HJ, Gohari AR, Bhatti MT. Loss of myelinated retinal nerve fibers from chronic papilledema. J Neuroophthalmol. 2008;28:219–221. doi:10.1097/WNO.0b013e3181772856 [CrossRef]18769289