Montorio, Daniela (2021) Optical Coherence Tomography Angiography as early vascular biomarker of Multiple Sclerosis. [Tesi di dottorato]

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Previous studies have reported the close clinical relationship between the brain and the retina because they are anatomically interconnected, show similar physiological features. Monitoring retinal vascularization may add important information to better understand the pathogenesis of neurological diseases and in particular multiple sclerosis (MS). The introduction of Optical Coherence Tomography Angiography (OCTA) in clinical practice allowed a non-invasive visualization of retinal microvasculature. This valid and reliable imaging technique could represent an reliable support in providing potential and useful biomarkers in MS pathogenesis and in disease progression. The present project aims to analyze in patients with initial demyelinating event (IDE), defined as the first neurologic symptom referable to demyelination in the central nervous system lasting for at least 48 hours, the retinal and choriocapillaris vascular networks by means OCTA and to detect their changes during a longitudinal study. In the first part of the study, the retinal and choriocapillaris vessel density (VD) was analyzed in macular and in peripapillary regions in IDE patients compared with matched relapsing-remitting multiple sclerosis patients and healthy subjects in order to define which OCTA parameters could be sensitive in identifying the first vascular changes in patients affected by early stages of MS. Thirty patients (20 with IDE and 10 with RRMS) and 15 controls were enrolled. IDE patients showed a lower VD in radial peripapillary capillary plexus compared with controls (coeff. β = -3.578; p= 0.002). RRMS patients displayed a lower VD in both superficial capillary plexus and radial peripapillary capillary plexus compared with controls (coeff. β = -4.955; p= 0.002, and coeff. β = -7.446; p<0.001, respectively). Furthermore, RRMS patients showed a decreased VD in radial peripapillary capillary plexus compared with IDE patients (coeff. β = -3.868; p= 0.003). Peripapillary region vessel density reduction might be considered as an early event in MS, and might be relevant as a biomarker of disease pathology. The second part of the study focused on the evaluation of retinal and choriocapillaris vascular changes in these IDE patients over two years follow up. OCTA parameters might represent useful vascular biomarkers to monitor the MS progression.  The VD was analyzed in superfical capillary plexus, deep capillary plexuses, choriocapillaris and radial peripapillary capillary plexus at baseline, at one and two years of follow up. Also the structural, spectral domain OCT parameters: ganglion cell complex (GCC) and retinal nerve fibre layer (RNFL) have been evaluated. A total of 30 eyes of 15 IDE patients (7 females, 8 males, mean age 28.4 ± 9.6 years) was enrolled. GCC and RNFL thicknesses did not show significant changes during follow up (p>0.05). The VD of OCTA parameters, except for choriocapillaris, showed not statistically significant reduction at the first year of follow up respect to baseline. At the second year significant lower values of VD were found in superficial capillary plexus, deep capillary plexus and radial peripapillary capillary plexus respect to the first year (coeff. β = -2.651, p= 0.018; coeff. β = -3.953, p= 0.015 and coeff. β = -1.810, p=0.005; respectively). In conclusion the retinal vascular rarefaction in early stages of MS could reflect a neurovascular degenerative progression even in absence of relapse activity during the follow up. In conclusion OCTA parameters could represent helpful biomarkers of the retinal perfusion damage before the appearance of neuroaxonal loss confirming the vascular dysfunction in pathophysiological mechanisms and in progression of MS. In the future, further analysis with larger cohorts and longer follow up with brain magnetic resonance imaging are needed to evaluate the changes in retinal blood flow and the relationship between the retinal microvascular impairment and the neuronal damage.

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