Surgical Removal of an Atypical Macular Epiretinal Membrane in Neurofibromatosis Type 2: Clinicopathologic Correlation and Visual Outcome

Macular epiretinal membranes (ERMs) are common manifestations in children with neurofibromatosis type 2 (NF2).¹ The ERMs in NF2 have been speculated to be hamartomatous in nature. Immunohistological techniques have rarely been used to characterize these ERMs.² The following case describes the clinical and histologic characteristics of a dense ERM in a case of NF2.

During a dilated fundus examination, a 2-year-old girl with confirmed NF2 and a history of esotropia and amblyopia in the left eye was noted to have a depigmented macular lesion in her left eye. The patient was undergoing patching therapy for amblyopia and was otherwise healthy. Family history was significant for neurofibromatosis affecting her father and paternal grandmother, the latter of whom had neoplasms of the brain, eyes, and auditory nerves that led to deafness, blindness, and death by age 34 years. On genetic testing, the child and her father were confirmed to have deletion of the NF2 promoter and exon 1, described as c.-854-?_45-?del.

Visual acuity was central, steady, and maintained in the right eye and central, steady, and unmaintained in the left eye. There was no afferent pupillary defect. Ocular versions were full with a left esotropia of 30 to 40 prism diopters. Cycloplegic refraction was +3.00 sphere OD and +2.00 sphere OS. Slitlamp examination showed normal anterior segments without cataracts or Lisch iris nodules. Fundus examination of the left eye revealed a gray, flat, macular lesion occupying an area of 2 × 2.5 disc diameters, partially obscuring underlying retinal and perifoveal vasculature (Figure 1A). A clinical diagnosis of a dense macular ERM in the left eye, possibly hamartomatous in etiology and possibly visually significant, was made. A small gray inner retinal opacity was also noted in the perifoveal region of the right eye (not shown). Magnetic resonance imaging of the brain and spine revealed no tumors.

Examination under anesthesia was performed. Spectral-domain optical coherence tomography (Bioptigen, Inc) of the left eye demonstrated a thickened ERM and underlying neurosensory retina with evidence of vitreous attachment to the membrane that caused slight elevation at its edges (

). Fluorescein angiography showed apparent absence of a foveal avascular zone due to perifoveal hypervascularity that crossed the horizontal raphe centrally (Figure 1B). The macular ERM showed no intrinsic vascularity. The patient underwent pars plana vitrectomy and ERM stripping in the left eye. The membrane was noted to be densely adherent to the macula but with a definite anatomic plane between the membrane and retina. As the membrane separated, so did a continuous posterior vitreous membrane, presumably a layer of the posterior cortical vitreous. The membrane was submitted for histologic studies. Light microscopy showed a highly cellular membrane with up to 4 layers of cells in some areas. There was weak staining for glial fibrillary acidic protein (Figure 2). There was insufficient specimen for adequate evaluation of periodic acid–Schiff or S-100 protein staining. The cells were of indeterminate origin; no astrocytes were identified in the limited amount of tissue available. Visual acuity was 20/20 OD and 20/125 OS 6 months after vitrectomy and continued refractive and amblyopia management that consisted of part-time occlusion of the right eye. The retinal vasculature in the left macula remained unchanged in appearance without recurrence of ERM.

To our knowledge, only 2 previous reports of histologic evaluation of an ERM in NF2 exist.^2,3 The ERMs in this condition appear clinically distinct from retinal astrocytic hamartomas but may coexist with them,⁴ leading to the speculation that they also may be hamartomatous. This speculation is supported by the histologic findings of McLaughlin et al² in which staining for glial fibrillary acidic protein and S-100 protein was demonstrated, supporting a glial origin. In our experience, weak staining for glial fibrillary acidic protein as noted in our case may also be observed in the majority of cells in some intracranial astrocytic hamartomas of NF2, although these contain identifiable astrocytes that stain more positively with glial fibrillary acidic protein. Thus, the limited body of evidence in existence suggests an astrocytic and therefore hamartomatous origin for ERMs in NF2.

We were unable to determine whether significant visual improvement resulted from our surgical intervention because of the difficulties in assessing visual function behaviorally in a 2-year-old child. Our enthusiasm for removal of such lesions is tempered by the unchanged anomalous retinal vascular pattern, possibly congenital, that persisted in the macula even after several months and the residual visual impairment observed in our case.

Correspondence: Dr Han, Department of Ophthalmology, Medical College of Wisconsin, 925 N 87th St, Milwaukee, WI 53226 (dhan@mcw.edu).

Funding/Support: This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York, and the Jack A. and Elaine D. Klieger Professorship, Medical College of Wisconsin, Milwaukee.

Additional Contributions: Deb Wahlers and Adam Dubis provided technical assistance in preparing the video.