Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis

Completed

• Conditions: Neurofibromatosis Type 1
• Interventions: Other: Electro-oculogram; Other: Full-field electroretinogram

• Registration Number: NCT04153344
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2019-11-04
• Study First Submitted QC: 2019-11-05
• Study First Posted: 2019-11-06
• Study Start: 2020-05-11
• Primary Completion: 2020-07-21
• Study Completion: 2020-07-21
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-20
• Last Update Posted: 2023-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Infrared hyperreflective area	Electro-oculogram	Patients with neurofibromatosis type 1 and with infrared hyperreflective areas
Infrared hyperreflective area	Full-field electroretinogram	Patients with neurofibromatosis type 1 and with infrared hyperreflective areas
No infrared hyperreflective areas	Full-field electroretinogram	Patients with neurofibromatosis type 1 and with no infrared hyperreflective areas
Controls	Electro-oculogram	Patients with no neurofibromatosis type 1
Controls	Full-field electroretinogram	Patients with no neurofibromatosis type 1
No infrared hyperreflective areas	Electro-oculogram	Patients with neurofibromatosis type 1 and with no infrared hyperreflective areas

Primary Outcome Measures

Name	Time	Method
Light/dark (Arden) ratio	12 months	Electro-oculogram : ratio between the light and dark potentials.
Dark trough value	12 months	Electro-oculogram : dark trough value (μV).

Secondary Outcome Measures

Name	Time	Method
Values of the amplitudes	12 months	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.
Values of the peak times	12 months	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.
Number and area of infrared hyperreflective areas	12 months	Infrared fundus picture.

Trial Locations

Locations (1)

Hôpital Necker-Enfants Malades; 🇫🇷 Paris, France