Clinical trial NCT04153344: Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis
Official title: Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neurofibromatosis Type 1
Keywords: Neurofibromatosis type 1
Infrared hyperreflective areas
Hyperactivity of the pigment epithelium
Electro-oculogram
Electroretinogram
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-11-06
Enrollment: 30
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients consulting the ophthalmology department of Necker-Enfants Malades Hospital:

* 10 patients with neurofibromatosis type 1 without infrared hyperreflective areas
* 10 patients with neurofibromatosis type 1 and infrared hyperreflective areas
* 10 control patients with no retinal disease

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dark trough value
timeFrame: 12 months
measure: Light/dark (Arden) ratio
timeFrame: 12 months
Secondary outcomes:
measure: Number and area of infrared hyperreflective areas
timeFrame: 12 months
measure: Values of the amplitudes
timeFrame: 12 months
measure: Values of the peak times
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Matthieu Robert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Dominique Brémond-Gignac, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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.