Choroidal neurofibromas in neurofibromatosis 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting 1 in 3500 people.[1] It is a multisystemic disorder with variable expressivity.[1] In the last decade, significant advances in the understanding of the pathophysiology of NF1 have been made.[2] The NIH clinical diagnostic criteria of NF1 require the presence of two of the following:[1]

1. Six or more café-au-lait macules over 5 mm in diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals

2. Two or more neurofibromas of any type or one plexiform neurofibroma

3. Freckling in the axillary or inguinal regions

4. Two or more Lisch nodules (iris hamartomas)

5. Optic glioma

6. A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis

7. First-degree relative (parent, sibling, or offspring) with NF-1 by the above criteria.

The most well-known ocular manifestation of NF1 is Lisch nodules.[2] However, an often overlooked yet highly sensitive finding among these patients are choroidal neurofibromas.[3] Choroidal neurofibromas are hamartomatous proliferations of neural crest cells within the choroid.[4] The imaging modality currently used to image choroidal neurofibromas has been near-infrared imaging (NIR).[5] Our case report demonstrates that SPECTRALIS^® MultiColor Imaging serves as an effective both alternative imaging tool and should be used in routine screening of NF1. While the current NIH diagnostic criteria do not acknowledge the presence of choroidal neurofibromas, recent studies have shown choroidal neurofibromas to have sensitivity of 97.5% in NF1 patients.[4] This value is in line with the sensitivity of the other currently established NIH diagnostic criteria of NF1.[1]

A 28-year-old female, with NF1, presented to the clinic with a history of reduced vision in the left eye. The patient had a family history of NF1, and her formal diagnosis of NF1 had already previously been made by the patient's primary care provider in accordance with the NIH diagnostic criteria. A thorough physical examination and documentation were therefore not conducted in the eye clinic. On ocular examination, best-corrected visual acuity was 20/20 in the right eye and 20/40 in the left eye. Intraocular pressure in the right eye was 13 mmHg and 14 mmHg in the left eye. On examination, Lisch nodules were visible in both eyes [Figure 1]. A cataract was also observed in the left eye. The anterior chamber was otherwise unremarkable. Dilated fundus ophthalmoscopy was unremarkable [Figure 2]. With multicolor retinal imaging, however, both eyes exhibited red patches distributed throughout the fundus [Figure 3] (SPECTRALIS^® MultiColor Module – Heidelberg Engineering, 10 Forge Parkway, Franklin, MA 02038, United States). No retinal abnormalities were detected on optical coherence tomography or fluorescein angiography in either eye. Based on these findings, the diagnosis of choroidal neurofibromas was made.

Figure 1.

Slit-lamp examination revealing Lisch nodules

Figure 2.

Slit-lamp imaging revealing unremarkable fundus

Figure 3.

Multicolor imaging revealing numerous red patches distributed throughout the fundus

Choroidal neurofibromas are benign hamartomatous proliferation of neural crest-derived cells of the choroid.[5] They have been reported to be present in between 82% and 97% of patients with NF1.[3,5] The sensitivity of multiple choroidal neurofibromas in NF1 is 97.5% compared to café au lait spots (98%) and Lisch nodules (86%).[3,4] Of note, only 2% of NF1 patients present with Lisch nodules in the absence of choroidal neurofibromas, whereas 13.75% of patients present with choroidal neurofibromas in the absence of Lisch nodules.[3] As a result, screening for choroidal neurofibromas has been suggested as a highly sensitive noninvasive screening tool for the detection of NF1.[5] Choroidal neurofibromas are poorly visualized on clinical slit lamp examination and have typically been visualized best on NIR. This case report suggests that standard fundus examination is likely to miss an essential diagnostic feature of NF1 in the eye. It also highlights how multicolor fundus imaging may be a highly effective tool in imaging of choroidal neurofibromas. Multicolor imaging should therefore be used in screening of NF1. Further studies should also be conducted to gauge the validity of choroidal neurofibromas as an additional diagnostic criterion for NF1.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.