Neurofibromatosis 2 is a neurocutaneous disorder that demonstrates unique ophthalmic manifestations. Several authors have noted a higher than expected incidence of epiretinal membranes in this population. In this brief case series, the authors document a series of optical coherence tomography (OCT) scans performed on three patients with neurofibromatosis 2 that demonstrated epiretinal membranes with atypical and distinctive characteristics. The membranes were unusually thick, with rolled edges extending into the vitreoretinal interface. The appearance of these membranes was distinct enough to establish a pattern. In one case, the unique OCT findings were the sole reason that the diagnosis of neurofibromatosis 2 was established. Ophthalmologists should consider neuroimaging in a child with any of these findings to rule out a diagnosis of neurofibromatosis 2, even if the patient is otherwise asymptomatic.
Optical Coherence Tomography Characteristics of Epiretinal Membranes in Neurofibromatosis 2
From the Bascom Palmer Eye Institute, Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, Florida.
Presented as a poster at the 24th Annual Meeting of the American Society of Retina Specialists, Cannes, France, September 10, 2006.
Address correspondence to Amy C. Schefler, MD, Bascom Palmer Eye Institute, P. O. Box 016880, Miami, FL 33101.
Accepted: August 20, 2007
Neurofibromatosis 2 is a neurocutaneous disorder demonstrating unique neurologic, dermatologic, and ophthalmic findings as a result of a mutation in a tumor suppressor gene located at 22q12.2. Patients with this syndrome develop a variety of benign tumors of the brain, orbit, and spinal cord.1 Ophthalmic manifestations include juvenile posterior subcapsular cataracts, peripheral wedge-shaped cortical cataracts, optic nerve meningiomas, combined hamartomas of the retina and retinal pigment epithelium, and unilateral Lisch nodules (iris hamartomas).2–4 Several authors have also described the presence of epiretinal membranes in these young patients in a significantly higher frequency than expected.2,3 However, the optical coherence tomography (OCT) characteristics of these epiretinal membranes have never been described. In this report, we describe the unique OCT characteristics of epiretinal membranes identified in three patients with neurofibromatosis 2.
A 7-year-old boy presented with a left esotropia since birth that had never been evaluated by an ophthalmologist. His best-corrected visual acuity was 20/20 in the right eye and 20/200 in the left eye.
Dilated fundus examination demonstrated a thin, translucent epiretinal membrane in the right macula and a thick, broader epiretinal membrane in the left eye (Fig. 1). OCT of the right eye revealed a thick epiretinal membrane across the surface of the macula with curled edges stretching into the vitreoretinal interface. There was resultant foveal contour distortion and mild retinal thickening. OCT of the left eye demonstrated a thicker epiretinal membrane with similar characteristics and marked retinal thickening (Fig. 2).
Figure 1. Color Fundus Photographs of Case 1. (A) Thin, Translucent Epiretinal Membrane in the Right Eye with 20/20 Visual Acuity. (B) Thick, Broader Epiretinal Membrane in the Left Eye with 20/200 Visual Acuity.
Figure 2. Optical Coherence Tomography (OCT) of Case 1. (A) Right Eye. Thick Epiretinal Membrane Laid Across the Surface of the Macula with Curled Edges Stretching into the Vitreoretinal Interface. Note Resultant Foveal Contour Distortion and Mild Retinal Thickening. (B) Left Eye. Thicker Epiretinal Membrane with Similar Characteristics and Marked Retinal Thickening with a Central Macular Thickness of 512 Microns.
Shortly after the ophthalmic examination, the patient developed tongue fasciculations and underwent evaluation by a pediatric neurologist. Magnetic resonance imaging (MRI) of the brain demonstrated small intracanalicular bilateral acoustic (CN VIII) schwannomas, a right hypoglossal (CN IX) schwannoma, and two intracranial meningiomas, one at the left sphenoid wing and one at the planum sphenoidale. These findings were consistent with neurofibromatosis 2. The patient has been observed with serial ophthalmic examinations including fundus photographs and OCT, all of which demonstrated no changes. The patient’s brain tumors remained clinically and radiographically stable at 26 months of follow-up.
A 9-year-old boy with a history of persistent fetal vasculature presented for ophthalmic examination. He had undergone cataract extraction in the left eye in Cuba at 14 months of age and was aphakic after surgery. According to the family, he retained good visual acuity postoperatively for several weeks with a contact lens. However, he developed a retinal detachment several weeks after surgery and never underwent surgical repair. His medical, surgical, and family history were non-contributory. He had no neurological symptoms.
On examination, his best-corrected visual acuity was 20/60+1 and light perception in the left eye. He had a 3+ relative afferent pupillary defect in the left eye. Intraocular pressures were normal. He had a fine bilateral horizontal jerk nystagmus consistent with a congenital nystagmus and a 12 prism diopter exotropia of the left eye.
Dilated fundus examination of the right eye revealed a broad epiretinal membrane stretching across the macula (Fig. 3). The left eye was found to have a fibrotic, chronic-appearing retinal detachment. OCT of the right eye demonstrated a thick epiretinal membrane across the surface of the macula with serpentine, curled edges stretching into the vitreoretinal interface (Fig. 4). There was resultant foveal contour distortion and mild retinal thickening. Stratus OCT (Carl Zeiss Meditec, Dublin, CA) images demonstrated similar findings in greater detail.
Figure 3. Color Fundus Photograph of Case 2. (A) Broad Epiretinal Membrane in the Right Eye. (B) Close-Up View of Perifoveal Tortuous Vessels.
Figure 4. (A) Optical Coherence Tomography (OCT) of the Right Eye of Case 2 with an Epiretinal Membrane, Several Cell Layers Thick, Laid Across the Surface of the Macula with Serpentine, Curled Edges Stretching into the Vitreoretinal Interface. (B) Stratus OCT (Carl Zeiss Meditec, Dublin, CA) of the Right Eye of Case 2 Demonstrating Similar Findings in Greater Detail.
As a result of the similarities noted between this patient’s OCT findings and patient 1’s OCT results, an MRI of the brain was performed. The MRI demonstrated multiple uniformly enhancing brain tumors, most consistent with meningiomas, and an acoustic schwannoma (Fig. 5). As a result of these findings, an MRI of the total spine was ordered. The MRI demonstrated multiple intradural extra-medullary spinal cord tumors, likely meningiomas or schwannomas, and one intradural intramedullary spinal cord tumor. A diagnosis of neurofibromatosis 2 was made.
Figure 5. Magnetic Resonance Imaging of the Brain with Gadolinium of Case 2 Demonstrating Multiple Benign Brain Tumors, Most Consistent with Meningiomas, and an Acoustic Schwannoma (acoustic Neuroma) on the Left. (A) Sagittal T1-Weighted Image. (B) Axial T1-Weighted Image.
One year later, the patient’s spinal cord tumor demonstrated interval growth on MRI scan and the patient underwent successful neurosurgical intervention. No surgical intervention was recommended for the epiretinal membrane in the right eye and the patient’s vision has remained stable for 16 months. Follow-up fundus examinations and OCT images have demonstrated no changes.
A 5-year-old girl with a suspicion of neurofibromatosis 2 on the basis of plexiform neurofibromas detected on physical examination by a geneticist presented for ophthalmic examination. The patient was noted to have a wedge-shaped sectoral cortical cataract in the right eye and a persistent hyaloid artery in the left eye with a best-corrected visual acuity of 20/80 in the right eye and 20/20 in the left eye. The patient underwent cataract surgery with intraocular lens implantation in the right eye and achieved a postoperative best-corrected visual acuity in the right eye of 20/30. The patient was observed with routine ophthalmic examinations.
Three years later, the patient underwent a routine screening MRI that revealed increased enhancement of the left optic nerve after contrast enhancement with gadolinium consistent with an optic nerve glioma. The patient underwent a repeat ophthalmic examination including OCT of both eyes, which revealed a thick epiretinal membrane with curled edges similar in appearance to the first two cases noted above (Fig. 6).
Figure 6. Optical Coherence Tomography of the Left Eye of Case 3 Demonstrating a Thick Epiretinal Membrane with Curled Edges Similar to Cases 1 and 2.
In these three cases, we observed the unique characteristics of epiretinal membranes in patients with neurofibromatosis 2. These membranes appeared to be several cell layers thick with curled serpentine-like edges stretching into the vitreoretinal interface. The unique appearance of these membranes on OCT was distinctive and, remarkably, this modality alone enabled the diagnosis of neurofibromatosis 2 in the second patient.
Epiretinal membranes are uncommon in children. The differential diagnosis of these lesions includes previous trauma, previous intraocular infection, posterior uveitis, retinal vascular disease, idiopathic epiretinal membrane, and epiretinal membrane associated with systemic diseases such as neurofibromatosis. Meyers et al. observed epiretinal membranes in 12 of 15 patients with neurofibromatosis 2.3 Histopathologic examination of one of the eyes in this series demonstrated an area of intraretinal glial proliferation with an overlying epiretinal membrane. Combined hamartomas of the retina and retinal pigment epithelium have been reported in neurofibromatosis 2, and epiretinal membrane formation is a recognized association with combined hamartoma of the retina and retinal pigment epithelium.2 Furthermore, several authors have proposed the existence of a spectrum of lesions in combined hamartoma of the retina and retinal pigment epithelium ranging from vascular malformations at one end to epiretinal membranes at the other.2
It is possible that our three patients’ lesions represented early or involuted hamartomas. However, the OCT characteristics of all but one of the eyes examined do not support this assertion. Only the left eye of patient 1 demonstrated a significant degree of intraretinal thickening that would be expected in a glial proliferation.
This study summarizes the OCT findings of the unusual epiretinal membranes identified in three patients diagnosed as having neurofibromatosis 2. Unique OCT characteristics of these membranes include unusual membrane thickness and serpentine-like edges stretching into the vitreoretinal interface. The ophthalmologist should consider neuroimaging in a child with any of these findings to rule out a diagnosis of neurofibromatosis 2 in an otherwise asymptomatic patient.
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- : Karadimas P, Hatzispasou E, Bouzas EARetinal vascular abnormalities in neurofibromatosis type 1. J Neuroophthalmol. 2003;23:274–275.