Multiple sclerosis and eye: Geometric complexity of the optic nerve head microvascularity-a pilot study

Multiple Sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system characterized by focal demyelinating lesions in the white matter of the brain or spinal cord. Lesions cause a range of vary symptoms depending on the location of lesions, and can include changes in autonomic, motor or sensory functions [1,2]. In particular, for the purpose of this article, MS often presents early ocular manifestations secondary to infl ammatory demyelination of the visual pathway, also causing optic neuritis [3]. We can recall that a majority of patients experience at least one episode of ocular involvement in the course of their disease [4,5].


Introduction
Multiple Sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system characterized by focal demyelinating lesions in the white matter of the brain or spinal cord. Lesions cause a range of vary symptoms depending on the location of lesions, and can include changes in autonomic, motor or sensory functions [1,2]. In particular, for the purpose of this article, MS often presents early ocular manifestations secondary to infl ammatory demyelination of the visual pathway, also causing optic neuritis [3]. We can recall that a majority of patients experience at least one episode of ocular involvement in the course of their disease [4,5].
Fractal analysis is emerging as a powerful tool to perform differential diagnosis and prognosis of the patients in pathology as well to improve the effectiveness and safety of patient care [6][7][8]. A lot of papers focused the usefulness of fractal analysis in the study of the retinal vessels [9][10][11][12][13][14]. In this paper we present a study of the microvascular pattern of eyes in MS patients, studying by fl uorangiography and fractal analysis the optic nerve head microvascularity.

Patients
Patients with unilateral optic neuritis without optic disc oedema (ON) affected by MS (n=6) were recruited from the Department of Medicine, Surgery and Neuroscience at the University of Siena. Three patients were female and three were male (mean age=32.3 years). In the control group, six patients were female and seven were male (mean age=48.7 years).
Each patient underwent a complete neuro-ophthalmic examination, including assessment of visual acuity, colour vision, papillary reaction, slit-lamp examination, applanation tonometry, Goldman visual fi eld testing, visual evoked potentials, dilated fundoscopy and fl uorescein angiogram. All patients were examined using a fl uorescein angiogram within the fi rst two weeks after they reported the fi rst symptoms and before treatments; all patients gave informed consent. Fluorescein angiogram of normal subjects (n=13) were used as controls. The protocol for this research project was approved by the Ethics Committee of the University of Siena and it conforms to the provisions of the Declaration of Helsinki, 1955 (as revised, Edinburgh, 2000).

Abstract
Multiple Sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system characterized by focal demyelinating lesions in the white matter of the brain or spinal cord. When MS affects the nerves in a person's eyes, it can cause Optic Neuritis (ON). We have investigated the microvascular pattern of the nerve head performing the evaluation of its fractal dimension (geometric complexity). Mean geometric complexity of the optic nerve head microvascularity in the affected eye in patients with multiple sclerosis resulted higher than in control normal subjects (p<0.01), and, moreover, the unaffected eye in patients with multiple sclerosis showed a geometric complexity that was not signifi cantly different from the one of the affected eye and higher than in control normal subjects (p<0.01). These data, if confi rmed in a higher number of patients, could show a characteristic microvascular pattern of the optic nerve head in subjects affected by multiple sclerosis, giving us a possible tool to identify earlier subjects that can develop multiple sclerosis.

Statistical analysis
Mann-Whitney's U test was used in order to compare the fractal indexes between the groups and to ascertain the statistical signifi cance; regression analysis was used to ascertain the log-log plot linearity.

Results
Geometric complexity of the optic nerve head microvascularity (affected eye) in MS patients showed a higher value than in normal subjects ( Figure 4, Table 1).

Geometric complexity in unaffected eyes of the MS patients
was not signifi cantly different from that of the affected eye ( Figure 5, Table 2). Both the eyes, affected and unaffected one, revealing a geometric complexity higher than in normal control subjects, p<0.01 (Tables 1,2).

Discussion
Fractal approaches grow in importance, year by year.
Fractality, the geometric concept related to highly irregular shapes that originates from simple iterated function with noninteger, or fractional, dimensions and a property known as   self-similarity, give to the pathologist a powerful method to support diagnosis and prognosis of the patients [6][7][8].
Multiple sclerosis results from an immune-mediated infl ammation and demyelination of axons. Lesions vary temporally and spatially, leading to the classic presentation of episodic neurologic symptoms. Among which, vision problems are potential early signs of MS. In effect, when MS affects the nerves in a person's eyes, it can cause optic neuritis. In effect, there is a known tendency for multiple sclerosis to develop in ON patients, being the risk of progression to multiple sclerosis within two years of an acute attack of ON. It is important to establish differential diagnosis among the different causes of ON [3], in order to treat patients earlier.
Our results show that the mean geometric complexity of the microvascular pattern of the optic nerve head is higher in the eye affected by ON than in the eye of control subjects, according to our previous results [16,17]. Moreover, in these MS patients  The values differed between the two groups (p<0.01). Mean value (standard deviation).  The values don't differ between the two groups (p=n.s.). Mean value (standard deviation). The geometric complexity of the unaffected eye in MS patients results higher than in normal control subjects (see Table 1, p<0.01).