Following RVCL-S to Treatment (FORT) - A natural history study of Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S)

Following RVCL-S to Treatment (FORT) - A natural history study of Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) - FORT

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON51098

Enrollment

Registered

2021-09-29

Start date

2022-11-04

Completion date

Unknown

Last updated

2025-09-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations RVCL-S

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: (Pre-)symptomatic mutation carriers: - Age: >= 18 years - Proven TREX1 mutation - Ability and willingness to provide written informed consent Control subjects: - Age: >= 18 years - Not genetically related to an RVCL-S patient or genetic testing has ruled out TREX1 mutations - Ability and willingness to provide written informed consent

Exclusion criteria

Exclusion criteria: For all subjects: - Subjects who do not want to be informed about unexpected findings that are considered serious, with prognostic or therapeutic consequences. This does not concern genetic test results. - Contra-indications for 3T/7T MRI as determined by the 7Tesla safety committee. (exclusion for a subpart of the study) For controls: - Presence of known (cerebro) vascular diseases such as overt manifestations of hypertensive/ atherosclerotic vascular disease, excessive anticoagulation (INR >3.0), CNS disorders, vascular malformation, vasculitis, blood dyscrasia, diabetes mellitus, severe clinical relevant carotid artery stenosis.

Design outcomes

Primary

Measure	Time frame
1. Long-term disease course in RVCL-S Long-term disease course will be determined by the occurrence of presumably RVCL-S related symptoms; by cognitive performance testing and by use of the modified Rankin Scale (mRS) and the Barthell Index. Standardised questionnaires will be used for screening for depression, anxiety and neuropsychiatric symptoms. Focal neurological symptoms will be evaluated by physical examination and 3T MRI. Ophthalmological examination will be performed for retinal involvement and organ involvement will be evaluated with venepuncture and urine examination (liver, kidney and thyroid function and blood count). 2. In vivo ocular and skin biomarkers Eyes: ocular examination will be performed, including visual acuity, intraocular pressure and fundus photography. With Optical Coherence Tomography scans the retinal nerve fibre layer thickness will be measured. With OCT-angiography scans the vessel density at the retina and the size of foveal avascular zone will be quantified. In patients with vascular retinopathy these scans will be combined with fluorescence angiography scans. Retinal oximetry is applied to calculate the oxygen saturation of the blood vessels of the retina. Skin: vessels will be visualized by nailfold capillaroscopy. Four images (1×1* mm in size) from the nailfold in each finger will be evaluated. The modified Maricq criteria will be used for grading the capillary morphology, density and distribution. 3. Retinal angiogenesis Optical Coherence Tomography Angiography (OCT-A) is a non-invasive technique that will be used to visualize the vascular structures of the retina and choroid three-dimensionally (without contrast).2 Quantitative assessment of vasculature of different segments and retinal layers, such as neovascularization or vascular dropout areas, and the creation of flow-density maps and calculations allows for comparison over time. 4. Long term progression of RVCL-S specific and common cerebral	—

Measure

Time frame

1. Long-term disease course in RVCL-S Long-term disease course will be determined by the occurrence of presumably RVCL-S related symptoms; by cognitive performance testing and by use of the modified Rankin Scale (mRS) and the Barthell Index. Standardised questionnaires will be used for screening for depression, anxiety and neuropsychiatric symptoms. Focal neurological symptoms will be evaluated by physical examination and 3T MRI. Ophthalmological examination will be performed for retinal involvement and organ involvement will be evaluated with venepuncture and urine examination (liver, kidney and thyroid function and blood count). 2. In vivo ocular and skin biomarkers Eyes: ocular examination will be performed, including visual acuity, intraocular pressure and fundus photography. With Optical Coherence Tomography scans the retinal nerve fibre layer thickness will be measured. With OCT-angiography scans the vessel density at the retina and the size of foveal avascular zone will be quantified. In patients with vascular retinopathy these scans will be combined with fluorescence angiography scans. Retinal oximetry is applied to calculate the oxygen saturation of the blood vessels of the retina. Skin: vessels will be visualized by nailfold capillaroscopy. Four images (1*×*1* mm in size) from the nailfold in each finger will be evaluated. The modified Maricq criteria will be used for grading the capillary morphology, density and distribution. 3. Retinal angiogenesis Optical Coherence Tomography Angiography (OCT-A) is a non-invasive technique that will be used to visualize the vascular structures of the retina and choroid three-dimensionally (without contrast).2 Quantitative assessment of vasculature of different segments and retinal layers, such as neovascularization or vascular dropout areas, and the creation of flow-density maps and calculations allows for comparison over time. 4. Long term progression of RVCL-S specific and common cerebral

—

Secondary

Measure	Time frame
Not applicable.	—

Countries

Netherlands

Outcome results