Healthy Subjects, Leber Hereditary Optic Neuropathy
Conditions
Keywords
Leber hereditary optic neuropathy, Metabolomics analysis, OCT, mtDNA mutation
Brief summary
Leber hereditary optic neuropathy (LHON), due to mitochondrial DNA (mtDNA) mutations, is responsible for profound visual impairment. However, there is evidence that optic nerve damage begins before vision declines. There is no biomarker to determine when optic nerve damage begins before visual acuity decline occurs. We hope that the analysis of metabolomics will reveal specific metabolomic profiles and different vitamin B3 and B9 levels depending on whether there are OCT signs of optic nerve damage in healthy patients with mtDNA mutations suggestive of LHON (11778, 3460 or 14484). The existence of an increase in the thickness of the optic fiber layer, whose normal values are well established, constitutes such a sign in favor of optic nerve damage.
Detailed description
The primary objective is to determine the metabolomic profile of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT. Given the difference in the prevalence of NOHL in men and women, with a sex ratio of 7 men to 3 women, this primary objective will be evaluated separately in these 2 groups of people. Secondary objectives include Determination of the cellular metabolomic profile of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT. Determination of the metabolomic profile in tears of healthy with an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optical fiber layer in OCT. Comparison of the serum and cellular metabolomic profile of healthy with an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) according to the existence or not of an increase in thickness of the optical fiber layer in macular OCT and with a control population without mtDNA mutation; Determination of a different clinical and paraclinical (OCT) evolution according to the metabolomic profiles. Determination of vitamin B3 and B9 levels of healthy with an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) according to the existence or not of an increase in the thickness of the optical fiber layer in macular OCT and with a control population without mtDNA mutation. For the reasons mentioned above, the secondary objectives will be studied separately in men and women with the constitution of 2 groups of patients.
Interventions
DIAGNOSTIC_TESTOptical coherent tomography
We compare the metabolomics profile of healthy patients based on the OCT appearance of the optic disc and RNFL
Sponsors
Hôpital Necker-Enfants Malades
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Patient carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with normal visual acuity and who has never had optic neuropathy, or Patient not carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with normal visual acuity and who has never had optic neuropathy; * Patient agreeing to undergo an OCT; * Patient agreeing to sign the informed consent; * Patient affiliated to French social protection (Primary Health Insurance Fund, CMU, etc.) or European social protection.
Exclusion criteria
* Patient with or having had optic neuropathy regardless of its etiology * Patient with glaucoma regardless of its etiology; * Patient not wanting to undergo OCT; * Patient not wanting to sign the informed consent; * Patient not affiliated with French social protection (Primary Health Insurance Fund, CMU, etc.) or European. * Patients less than 18 years old or over 60 years old * Pregnant patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolomic profile of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT | one year | Results of the metabolomics analysis in the different groups established according to the appearance of the OCT and gender in healthy patients carrying mtDNA mutations suggestive of LHON (11778, 3460 or 14484). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metabolomic profile in tears of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT. | one year | Results of the metabolome established on tears in the different groups established according to the appearance of the OCT and the gender in healthy patients carrying mtDNA mutation evocative of NOHL (11778, 3460 or 14484). |
| Cellular metabolomic profile of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT. | one day | Results of the cellular metabolome established on leukocytes in the different groups established according to the appearance of the OCT and the gender in healthy patients carrying mtDNA mutation evocative of NOHL (11778, 3460 or 14484). |
| To assess a visual acuity evolution depending on the metabolomic profiles. | one year | Monitoring of the clinical evolution of visual acuity for one year in the different groups established according to the OCT appearance and gender in healthy patients carrying mtDNA mutations suggestive of NOHL (11778, 3460 or 14484). comparison with metabolomic profiles. |
| To assess a different OCT evolution depending on the metabolomic profiles. | one year | Monitoring of the evolution of visual acuity and OCT data for one year in the different groups established according to the OCT appearance and gender in healthy patients carrying mtDNA mutations suggestive of NOHL (11778, 3460 or 14484). comparison with metabolomic profiles. |
| Comparison of vitamin B3 and B9 levels in healthy patients with an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) according to macular OCT data and with a control population without mtDNA mutation. | one year | Measurement of blood levels of vitamins B3 and B9 in different groups established according to OCT appearance and gender in healthy patients carrying mtDNA mutations suggestive of NOHL (11778, 3460 or 14484). |
Countries
France
Contacts
Primary Contactchristophe Orssaud, MD
Backup ContactPascal Reynier, MD PhD
Outcome results
None listed