Abstract
Purpose :
The eye is a uniquely accessible organ with very sophisticated imaging systems for evaluation of it’s anatomy and vasculature in particular. The tight junction protein claudin-5 which is richly expressed at the inner blood retinal barrier (iBRB) is also expressed at the level of the blood brain barrier(BBB). Developing software which could use ocular vasculature as an indicator of BBB integrity has applications in a number of neurodegenerative disorders and neurological insults. We sought to evaluate the integrity of the in neurological disorders (CSF1R mutation and Visual Snow) using FOVAS (Fluorescent Ocular Vascular Analysis Software), a novel quantitative analysis software tool for FFA studies.
Methods :
3 subjects were recruited, 1 with adult onset leukoencephalopathy with axonal spheroids (ALSP) – (an autosomal dominant CSF1R mutation) and 2 with visual snow syndrome. Fundus fluorescein Angiography (FFA), Optical Coherence Tomography (OCT) and fundal autofluorescence were performed using the Heidelberg SPECTRALIS. Sodium fluorescein (1 mg/mL) was administered and images obtained at 1 minute, 2 minutes, 4 minutes and 5 minutes post injection. FFA and OCT images were obtained with a 30 degree angle of view and 73 line cuts were acquired. Heidleberg Eye Explorer (HEYEX) was used to capture images. FFA analysis and quantification was conducted using FOVAS against a threshold determined from the fluorescein signal of n = 33 normal healthy controls (aged 18 -30).
Results :
In the subject with a CSF1R mutation, FFA images showed a significantly increased fluorescein signal in the peri- and para-foveal regions of the macula. In both subjects with visual snow, FFA images showed a significantly increased fluorescein signal in the foveal, peri, para and extra foveal regions suggesting an increased iBRB permeability in this disorder. FOVAS analysis suggests a potential pathology involving tight junctional proteins of the endothelium.
Conclusions :
We report increased permeability of the iBRB in a single case of an individual with a condition in involving a dominant acting mutation in the gene CSF1R and in a small case series of patients with Visual Snow syndrome following FOVAS analysis. We conclude that with the development of FOVAS and a robust dataset demonstrating ‘normal’ inner retinal vascular integrity, we can potentially expedite the study of blood tissue barrier disruption in neurodegenerative diseases.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.