Ophthalmic imaging in RVCL

Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL) is a monogenic
neurovascular disorder caused by heterozygous TREX1 mutations, and is
characterized primarily by progressive loss of vision due to a retinal
vasculopathy. In addition, a wide range of cerebral and systemic conditions,
including intracerebral mass lesions and white matter lesions with associated
focal neurological symptoms and cognitive impairment, migraine (primarily
without aura), Raynaud*s phenomenon, anaemia and liver and kidney dysfunction
can be detected. The consecutive disease stages of RVCL, especially the early
stages, remain to be identified. Storimans et al. described retinopathy in a
Dutch family. Retinopathy including central and peripheral microangiopathy,
areas of capillary non-perfusion, haemorrhages, cotton wool spots and occlusion
of large retinal vessels were reported in 22 of the 110 family members. Years
later the affected family members turned out to be TREX1 mutation carriers.
It is hypothesized that RVCL patients, like patients with neurodegenerative
diseases, undergo a prolonged presymptomatic period where histological changes
are progressively accumulating without overt signs and symptoms.
Apart from fundoscopy and fundus imaging, optical coherence tomography (OCT)
nowadays plays a key role in monitoring the health status of the retina. The
OCT is a non-invasive imaging test that uses back-reflected infrared light to
take cross-section pictures of the retina. The OCT is used for detecting age
related macular degeneration (AMD), which is a leading cause of severe central
visual acuity loss in one or both eyes in people over 50 years of age. In AMD,
amyloid depositions can be found in the macular region which relate to the
atrophy of the retinal pigment layer. In patients with neurodegenerative
diseases like Alzheimer*s disease (AD) it has been reported that OCT visualized
generalized reduction of the peripapillary retinal nerve fiber layer (RNFL)
thickness and total macular volume has been reported. OCT might show
abnormalities in RVCL without clear presence of symptoms related to RVCL.
So far, no studies with OCT in combination with fundus imaging have been
performed in patients with RVCL. Retinopathy may also be present in a
presymptomatic stage and this could assist in the search for adequate treatment
of early stages in the disease.

To detect ophthalmic differences between patients and controles. To detect
(early) changes in the retina in (pre)symptomatic RVCL disease carriers, in
order to find a *biomarker* for disease stage and progression.

We will perform an observational cross-sectional diagnostic study in RVCL
mutation carriers versus age and sex matched control subjects. The study will
take place at the Leiden University Medical Center (LUMC). Ophthalmic
examination will be performed in all subjects, including: * Visual acuity test
* Intraocular pressure * Slit lamp examination * Fundoscopy * Fundus
photography * OCT-scan: Mydriasis is required for fundoscopy and fundus
photography. Therefore mydriatic and cycloplegic eye drops (Tropicamide 0.5%
eye drops and Phenylephrine hydrochloride 5.0% eye drops) will be given to all
subjects. It takes approximately 15 to 20 minutes prior for these eye drops to
have maximum effect and dilate the pupil. These eye drops have a duration of
effect of approximately 5 to 8 hours. The fundus photographs will be assessed
according to classification of diabetic retinopathy. The OCT scans will be
evaluated according to the classification of AMD described by Ferris the 3rd en
colleagues. The total duration of all the tests will be approximately 1.5 hour.

For the ophthalmological tests the pupils will be dilated, which temporarily
gives a slightly decreased vision and/or mild to moderate photofobia for 5-8
hours.