Frequency of choroidal abnormalities in neurofibromatosis type 1

doi:10.1016/S0140-6736(00)02716-1

The Lancet

Volume 356, Issue 9234, 16 September 2000, Pages 988-992

https://doi.org/10.1016/S0140-6736(00)02716-1 Get rights and content

Summary

Background

Choroidal neurofibromatosis is thought to be a rare form of neurofibromatosis that involves the eyes. The development of infrared light examination with a scanning laser ophthalmoscope (SLO) and indocyanine-green fundus angiography has allowed examination of the choroid. We studied choroidal abnormalities in patients with neurofibromatosis 1 and compared their frequency with that of other ocular abnormalities.

Methods

We examined 33 eyes of 17 consecutive patients diagnosed with neurofibromatosis 1 by conventional ophthalmoscopy and by non-invasive infrared monochromatic light with confocal SLO. 76 eyes of 39 age-matched controls were examined similarly by confocal SLO. 21 digital fluorescein and indocyanine-green angiographies were obtained from 11 adult patients, and 77 angiograms were obtained from age-matched controls.

Findings

Infrared monochromatic light examination by confocal SLO showed bright multiple patchy regions at and around the entire posterior pole of all 33 eyes examined. All bright patchy regions seen in adult patients corresponded to hypofluorescent areas on their indocyanine-green angiograms. However, no abnormalities were noted in any patient at corresponding areas under conventional ophthalmoscopic examination or fluorescein angiography. In SLO and indocyanine-green studies, controls and control angiograms showed no choroidal abnormalities. Iris nodules were noted in 25 eyes (76%) of 14 patients (82%) and eyelid neurofibroma in five patients (29%).

Interpretation

The bright patchy regions noted under infrared fundus examination and the corresponding hypofluorescent areas seen on indocyanine-green angiograms are probably of choroidal origin. The high frequency (100%) of these abnormalities suggests that the choroid is one of the structures most commonly affected by neurofibromatosis 1.

Introduction

Neurofibromatosis type 1, first described by von Recklinghausen,¹ is one of the most common inherited disorders, occurring in about one in 3000 births.² Since the original National Institutes of Health Consensus Development Conference in 1987,³ there has been substantial progress towards a more complete understanding of the molecular basis of neurofibromatosis.⁴ Neurofibromatosis 1 is now defined as a neurocristopathy, a disorder involving aberrant proliferation of multiple tissues derived from neural-crest cells.2, 5, 6, 7 Many studies have reported ocular manifestations of neurofibromatosis 1. However, there have been few reports on choroidal abnormalities,8, 9 except those of histopathological studies on enucleated eyes.10, 11, 12, 13, 14, 15, 16

Choroidal neurofibromatosis8, 9, 10, 11, 12, 13, 14, 15 is thought to be a rare form of neurofibromatosis that affects the eyes.8, 9, 13, 14, 15, 16 The rarity of this disorder is due to the limitations of conventional ophthalmoscopic fundus examination and fluorescein fundus angiography for depicting the choroidal structure through the melanin-loaded retinal-pigment epithelium, which blocks visible light. Since infrared light penetrates the retinal-pigment epithelium better than visible light, infrared monochromatic light examination of the fundus by scanning laser ophthalmoscopy (SLO) can show choroidal abnormalities.¹⁷ Indocyanine-green fundus angiography (IGFA), which also uses infrared light for excitation of a fluorescent indocyanine-green dye, has overcome the limitations of fluorescein angiography for imaging of the choroidal vasculature.18, 19, 20, 21 Thus, we investigated the fundi of consecutive patients diagnosed with neurofibromatosis 1 by SLO and by IGFA and compared the prevalence of abnormalities seen with the prevalence of other ocular abnormalities.

Section snippets

Methods

We studied 33 eyes of 17 patients (seven male, ten female; mean age 29·2 years, range 6–61). Six patients (two boys, four girls) were under 12 years of age (table). These consecutive patients were seen in our clinic between July, 1998, and July, 1999. One eye of one patient was not included in the study because of phthisis bulbi. The diagnosis of neurofibromatosis 1 was based on stringent National Institutes of Health criteria. Each patient underwent a general ophthalmological examination in

Results

He-Ne laser monochromatic light examinations of the fundi under confocal SLO and conventional fundus examination, including biomicroscopic examination and fundus colour photography, did not show any remarkable changes except the right eye of patient 5 with neuro-fibromatosis 1, in which myopic chorioretinal atrophy was noted at the posterior pole. However, infrared monochromatic light examination under confocal SLO showed bright patchy regions (figure 1) at and around the posterior pole of all

Discussion

Infrared light can penetrate the retinal-pigment epithelium into the choroid better than He-Ne light. Therefore, the presence of the bright patchy regions seen with infrared light and the absence of such regions under He-Ne light examination indicates that the patchy regions are of choroidal origin. This assertion is also supported by the absence of remarkable findings in conventional ophthalmoscopic or biomicroscopic fundus examinations or on fluorescein angiograms, and by the presence of

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Early ReportFrequency of choroidal abnormalities in neurofibromatosis type 1

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Surv Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Ber die Multiplen Fibrome der Haut und Ihre Beziehung zu den Multiplen Neuromen

National Institutes of Health Consensus Development

Arch Neurol

The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2

JAMA

The pathophysiology of neurofibromatosis

N Engl J Med

Coexistence of 3 tumors of neural crest origin: neurofibroma, meningioma and uveal malignant melanoma

Arch Ophthalmol

Clinical application of digital indocyanine green angiography in choroidal neurofibromatosis

Ophthalmologica

Early Report
Frequency of choroidal abnormalities in neurofibromatosis type 1