Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis

Neurofibromatosis Type 1 Clinical Trial

— NEF-1  

Official title:

Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04153344
• Other study ID #: APHP190937
• Secondary ID: 2019-A02526-51
• Status: Completed
• Start date: May 11, 2020
• Est. completion date: July 21, 2020

Study information

• Verified date: March 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objective of this study is to study the function of the pigment epithelium in patients with neurofibromatosis type 1 using electro-oculogram to confirm abnormally high values reported in previous studies, but also to correlate this hyperactivity of the pigment epithelium with the presence and size of choroidal hyperreflective areas observed in infra-red imaging of the fundus.

The hypothesis of the study is that the function of the pigment epithelium measured by the electro-oculogram correlates with the surface of choroidal hyperreflective areas. Finally, the potential consequences of a supra-normal function of the pigment epithelium on the global retinal function are not known. A full-field electroretinogram will evaluate the global neurosensory retinal function.

Description:

Patients with neurofibromatosis type 1 have numerous eye problems: glioma of the optic pathways, Lisch nodules, palpebral involvement by plexiform neurofibromas, orbital dysplasia, etc. With the emergence of multimodal imaging in ophthalmology a new ocular involvement has been described: choroidal hyperreflective areas. They are located in the most superficial layers of the choroid, adjacent to the retinal pigment epithelium, visible only on infra-red imaging of the fundus. These areas are frequently observed, about 90% in adults and 70 to 80% in children. With a sensitivity of 0.83 and a specificity of 0.96, these lesions would have their place as a diagnostic criterion for neurofibromatosis type 1.

In parallel, two successive studies have evaluated the function of the retinal pigment epithelium using electro-oculograms; they showed in patients with neurofibromatosis type 1 a significant increase in the Arden ratio, reflecting hyperactivity of the pigment epithelium.

The objective of this study is to study the function of the pigment epithelium in patients with neurofibromatosis type 1, using electro-oculogram to confirm these abnormally high values, but also to correlate this hyperactivity of the pigment epithelium to the presence and total area of choroidal lesions observed in infra-red imaging of the fundus.

The hypothesis of the study is that the function of the pigment epithelium measured by the electro-oculogram correlates with the surface of the choroidal hyperreflective areas. Finally, the potential consequences of a supra-normal function of the pigment epithelium on the global retinal function are not known. A full-field electroretinogram will evaluate the global neurosensory retinal function.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 21, 2020
• Est. primary completion date: July 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years and older

Eligibility

Inclusion Criteria:

• Patients with neurofibromatosis type 1, aged 7 years or older:

• Presence of hyper-reflective choroidal lesions in infra-red imaging in the group with choroidal lesions.

• Absence of hyper-reflective choroidal lesions in infra-red imaging in the group without choroidal lesions.

• Control patients free from retinal or choroidal pathology, matched for age to patients in the group with neurofibromatosis type 1.

• Patients consulting the ophthalmology department of Necker-Enfants Malades Hospital.

• Non-opposition of the holders of the parental authority and the minor patient; non-opposition of the major patient.

Exclusion Criteria:

• Impossibility to perform an electro-oculogram, especially because of an oculomotor disorder, or an electroretinogram, for example because of hyperactivity.

• Significant impairment of visual function.

• Retinal pathology proved.

Related Conditions & MeSH terms

• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis Type 1

Intervention

Other:
• Electro-oculogram
Electrophysiological recording of changes in electrical potential across the retinal pigmentary epithelium during successive periods of dark and light adaptation, according to ISCEV standards. Results will comprise dark trough value and light/dark (Arden) ratio.
• Full-field electroretinogram
Electrophysiological recording of retinal function. Results will comprise amplitudes and latencies of each electroretinography response (dark-adapted 0.01, dark-adapted 3.0, dark-adapted 10.0, dark-adapted 3.0 oscillatory potentials, light-adapted 3.0, light-adapted 3.0 flicker).

Locations

Country	Name	City	State
France	Hôpital Necker-Enfants Malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (3)

Lubinski W, Zajaczek S, Sych Z, Penkala K, Palacz O, Lubinski J. Electro-oculogram in patients with neurofibromatosis type 1. Doc Ophthalmol. 2001 Sep;103(2):91-103. doi: 10.1023/a:1012271206258. — View Citation

Touze R, Abitbol MM, Bremond-Gignac D, Robert MP. Function of the Retinal Pigment Epithelium in Patients With Neurofibromatosis Type 1. Invest Ophthalmol Vis Sci. 2022 Apr 1;63(4):6. doi: 10.1167/iovs.63.4.6. — View Citation

Viola F, Villani E, Natacci F, Selicorni A, Melloni G, Vezzola D, Barteselli G, Mapelli C, Pirondini C, Ratiglia R. Choroidal abnormalities detected by near-infrared reflectance imaging as a new diagnostic criterion for neurofibromatosis 1. Ophthalmology. 2012 Feb;119(2):369-75. doi: 10.1016/j.ophtha.2011.07.046. Epub 2011 Oct 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dark trough value	Electro-oculogram : dark trough value (µV).	12 months
Primary	Light/dark (Arden) ratio	Electro-oculogram : ratio between the light and dark potentials.	12 months
Secondary	Number and area of infrared hyperreflective areas	Infrared fundus picture.	12 months
Secondary	Values of the amplitudes	Electroretinogram : values of the amplitudes (µV) of a- and/or b-waves for dark-adapted 0.01, dark adapted 3.0, dark-adapted 10.0, dark-adapted 3.0 oscillatory potentials, light-adapted 3.0, and light-adapted 3.0 flicker.	12 months
Secondary	Values of the peak times	Electroretinogram : values of the peak times (ms) of a- and/or b-waves for dark-adapted 0.01, dark adapted 3.0, dark-adapted 10.0, dark-adapted 3.0 oscillatory potentials, light-adapted 3.0, and value of the peak-to-peak time (ms) for light-adapted 3.0 flicker.	12 months