Author Affiliations: John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences (Drs Shelton, Digre, Warner, and Katz and Mr Gilman) and Clinical Neurosciences Center, Department of Neurology (Drs Shelton, Digre, Warner, and Katz), University of Utah, Salt Lake City. Dr Shelton is now with Intermountain Eye and Laser Center, Boise, Idaho.
Myelinated retinal nerve fiber layers (RNFLs) are relatively common and generally benign. They appear as white, sharply demarcated patches on the surface of the retina that obscure the underlying retinal vessels. They have frayed or feathered borders that correspond in shape and distribution to ganglion cell axons. Myelination of the RNFL is often congenital but can be acquired or even progress in childhood or adolescence.1 Also, partial or total regression of the myelinated RNFL has been observed after injury to the optic nerve.2
Curiosity about the etiology of this superfluous myelination abounds, but the pathophysiology remains largely unknown. Normal myelination typically progresses from the chiasm to the optic nerve from the eighth month of gestation until birth and then stops at the lamina cribrosa. Proposed factors for normal inhibition of myelination in the human retina include the structure of the lamina cribrosa itself, plasma proteins leaking from the choroidal circulation that may stimulate the differentiation of oligodendrocytes, and factors released by type 1 astrocytes that inhibit oligodendrocyte migration.3
Many of the imaging characteristics of RNFL myelination have not yet been described. One report of optical coherence tomographic (OCT) images of myelinated RNFL in 2 patients with high myopia and small optic nerves showed reduced retinal thickness in the same distribution of the myelination.4 To our knowledge, there are no published reports of OCT findings in eyes without high myopia and abnormal optic nerves (based on an English-language PubMed search including “myelinated nerve fiber layer AND OCT,” “retina nerve fiber layer myelination,” “myelinated retina nerve fiber layer,” “optical coherence tomography AND myelin,” and “autofluorescence AND nerve fiber layer”). Herein, we describe the retrospectively obtained red-free, fluorescein, OCT, infrared, and autofluorescence characteristics of these structures in 4 eyes.
A 14-year-old girl was referred to the neuro-ophthalmology service because of an abnormal appearance of her left optic disc. She was otherwise healthy and asymptomatic. A color fundus photograph (Zeiss FF-4; Carl Zeiss Meditec) of the left eye was taken in 2011 (at age 14 years) (Figure, A). A red-free image (Zeiss FF-4) highlights the white appearance of the myelinated RNFL (Figure, B). Infrared imaging (Spectralis; Heidelberg Engineering) highlights the white appearance of the myelinated RNFL (Figure, C). Autofluorescence imaging (Spectralis) reveals a dark area in the region of the myelinated RNFL (Figure, D). An OCT image (Spectralis) shows a thickened RNFL in areas of the myelination (Figure, E). A color fundus photograph of the left eye from 2007 (at age 10 years) indicates that development of the peripapillary myelinated RNFL occurred sometime between ages 10 and 14 years and also reveals that the pigmented spot was unchanged (Figure, F).
Figure. Imaging findings in a 14-year-old girl with retinal nerve fiber layer (RNFL) myelination of her left optic disc. A, Color fundus photograph (Zeiss FF-4; Carl Zeiss Meditec) of the left eye from 2011 (at age 14 years). B, Red-free image (Zeiss FF-4) highlights the white appearance of the myelinated RNFL. C, Infrared imaging (Spectralis; Heidelberg Engineering) highlights the white appearance of the myelinated RNFL. D, Autofluorescence imaging (Spectralis) reveals a dark area in the region of the myelinated RNFL. E, Optical coherence tomographic image (Spectralis) shows a thickened RNFL in areas of the myelination. F, Color fundus photograph of the left eye from 2007 (at age 10 years), provided by Timothy Byers, MD, PhD, indicates that development of the peripapillary myelinated RNFL occurred sometime between ages 10 and 14 years and also reveals that the pigmented spot was unchanged.
Color fundus, red-free, infrared, autofluorescence, and OCT images are shown for an 83-year-old man (eFigure 1), a 55-year-old woman (eFigure 2), and a 55-year-old man (eFigure 3).
Administrative review by the University of Utah Institutional Review Board was obtained. The project was determined to not meet the definition of human subjects research and therefore did not require further institutional review board oversight.
The imaging characteristics of these patients' myelinated RNFLs are similar in almost all respects.
On infrared and red-free imaging, the myelinated RNFL stands out as white. Myelin consists largely of lipid, so this suggests that red-free imaging (488 nm) and infrared imaging (820 nm) are sensitive to structures with high lipid content. The high lipid content of myelin is also most likely responsible for the blocking effect created on fluorescein angiography.
Fundus autofluorescence (488 nm) works by detecting the natural fluorescence occurring from lipofuscin, a toxic product of photoreceptor cells that accumulates in lysosomes of unhealthy retinal pigment epithelial cells. Myelinated RNFL appears dark on autofluorescence, most likely because it blocks detection of underlying fluorescent material such as lipofuscin.
The thickened RNFL seen in areas of myelination on high-definition OCT suggests that the myelination creates bulk around the axon. However, it is also possible that the axon itself is larger within myelinated regions of RNFL, as was found to be the case in a histopathological study of myelinated RNFL.5
Myelination of the RNFL can be mistaken for other, more serious conditions including cotton-wool spots, branch retinal artery occlusion, peripapillary epiretinal membrane, retinal pigment epithelium detachment, retinal infiltrate, and even retinoblastoma with leukokoria. Knowledge of the imaging characteristics specific to myelinated RNFL may be helpful in differentiating it from other, more serious conditions. We hope this small case series will inspire future reports highlighting the specific findings on ophthalmic imaging of other retinal entities. It is important to recognize the generally benign nature of these lesions to avoid additional evaluations and spare the patient unnecessary anxiety.
Correspondence: Dr Shelton, Intermountain Eye and Laser Center, 999 N Curtis Rd, No. 205, Boise, ID 83706 (firstname.lastname@example.org).
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported in part by an unrestricted grant to the Department of Ophthalmology and Visual Sciences, University of Utah from Research to Prevent Blindness.
Additional Contributions: We thank Timothy Byers, MD, for referral of this interesting case, and we thank all the ophthalmic photographers at the John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah for their great assistance in obtaining all the images in this case series.
Shelton JB, Digre KB, Gilman J, Warner JEA, Katz BJ. Characteristics of myelinated retinal nerve fiber layer in ophthalmic imaging: findings on autofluorescence, fluorescein angiography, infrared, optical coherence tomography, and red-free images.. JAMA Ophthalmol.. 2013;131(1). doi:10.1001/jamaophthalmol.2013.560.
eFigure 1. These photographs are from the right eye of an 83-year-old man.
eFigure 2. These photographs are from the right eye of a 55-year-old woman.
eFigure 3. These photographs are from the left eye of a 55-year-old man.
Shelton JB, Digre KB, Gilman J, Warner JEA, Katz BJ. Characteristics of Myelinated Retinal Nerve Fiber Layer in Ophthalmic ImagingFindings on Autofluorescence, Fluorescein Angiographic, Infrared, Optical Coherence Tomographic, and Red-free Images. JAMA Ophthalmol. 2013;131(1):107-109. doi:10.1001/jamaophthalmol.2013.560