Vascular Mechanisms Implicated In
Optic Neuritis & Multiple Sclerosis

Objective
To investigate patients with acute Optic Neuritis (ON) for changes of the Retinal Veins.

Material And Methods
Seventy-six patients with acute ON were extensively Neuro-Ophthalmologically examined.

Results
Multiple Sclerosis (MS) was found in 41 patients of whom 1 had PeriPhlebitis Retinae (PR) and 2 had Venous sheathing (VS).

Probable MS was found in 15 patients without prior symptoms of MS. One had PR and VS, and 2 had VS. Twenty patients had MonoSymptomatic ON, none had Retinal changes.

Conclusion
Changes of the Retinal Veins should alert the clinician to a probable diagnosis of MS. ON appears frequently as the initial symptom of MS.

Our observation of VS in these patients suggest that clinically silent Retinal Disease activity had occurred prior to the ON.

This study was performed in order to verify the prevalence of Retinal PeriPhlebitis and other Ocular changes.

In a well-defined population of Multiple Sclerosis (MS) patients, and to correlate the presence of these features with some clinical variables which characterize the disease.

110 MS-affected subjects were submitted to a standard Ophthalmologic Examination including a BioMicroscopical evaluation of the Fundus Oculi.

The prevalence of Retinal sheathing in MS patients was found to be nearly 36%.

It is significantly higher in patients evaluated in an active phase of the disease than in those examined in a stationary phase.

Purpose
To describe the Ocular pathologic changes in Multiple Sclerosis (MS), with attention to its effects on the Uveal Tract and Retinal Veins.

Methods
Cases of 26 patients with MS and 3 patients with NeuroMyelitis Optica were reviewed; Retinal Trypsin digestion was performed on remaining wet tissue for 20 of these patients.

Eyes were specifically examined for inflammation of the Retinal vessels, Uveal Tract, Retina, Optic Nerve, and Pars Plana. Specimens were also examined for Atrophy of the Optic Nerve, Ganglion Cell, and Nerve Fiber layers.

Results

1. Atrophy of the Nerve Fiber and Ganglion Cell layers was present
   • In 73% of the cases with MS and correlated with Optic Nerve Atrophy
2. Choroiditis was present in 11.5%;
3. BiLateral Cyclitis without other foci of inflammation was present in 1 case;
4. Retinal Phlebitis was present in 20%
   • Most of which were only identified after Trypsin digestion
5. Optic Nerve inflammation was present in two of the patients with NeuroMyelitis Optica

Conclusion
Uveitis and Retinal Phlebitis are manifestations of MS. Trypsin digestion with microscopic examination is a sensitive method of testing for Phlebitis, which may explain why the frequency found in this series is higher than in others.

These lesions are similar to the PeriVenular cuffing that occurs in the Central Nervous System in MS.

Twenty-four patients with clinically defined Multiple Sclerosis were prospectively studied with the aim of establishing the frequency of Retinal PeriPhlebitis.

In three cases (12.5%) Retinal PeriPhlebitis was observed. None of the patients with Multiple Sclerosis and Retinal PeriPhlebitis presented a severe form or Progressive course of the disease.

However, in one patient it caused complete Unilateral Amaurosis. Aggressive ImmunoSuppressive treatment was effective in one case.

Given the absence of Myelin in the Retina, the presence of Retinal PeriPhlebitis suggests the existence of a Vascular mechanism in the PathoGenesis of Multiple Sclerosis.

A systematic study of the frequency of Retinal Vascular abnormalities and cells in the Media has been made in 50 patients presenting with Acute Optic Neuritis.

Abnormalities were found in 14 (Fluorescein leakage in 10, Perivenous sheathing in 6, cells in the Vitreous in 6 and in the Anterior Chamber in 4; in 2 the cells in the Media were seen without Vascular changes).

After a mean follow up of 3.5 years Multiple Sclerosis (MS) had developed in 8/14 patients with Vascular abnormalities and/or evidence of inflammation and in 5/32 without; the difference is significant (P less than 0.02).

The occurrence of PeriVenular abnormalities in a region free of Myelin and Oligodendrocytes provides evidence.

That the Vascular changes in MS can occur independently of contiguous DeMyelination, and may be the primary event in the formation of a new lesion.

We report five cases of Multiple Sclerosis (MS) and three cases of Allied DeMyelinative diseases starting during childhood.

Three of the MS patients presented with atypical initial symptoms, such as Acute Encephalitis or Myelitis, making an early clinical diagnosis difficult.

OphthalMologic symptoms were noted in four of MS children, and in two with allied DeMyelinative Diseases.

Therefore, if a child shows Ophthalmologic symptoms (i.e. Optic Neuritis, OphthalMoplegia), Brain Magnetic Resonance Imaging (MRI) should be conducted for the differential diagnosis of MS and other DeMyelinative Diseases.

CerebroSpinal Fluid analysis is not useful for the initial diagnosis of MS.

Because Pleocytosis and increase of OligoClonal IgG Band in CerebroSpinal Fluid are seen in both MS and other DeMyelinative Disorders.

However, Neuron Specific Enolase (NSE) is slightly higher in the latter than in the former.

T₂-weighted MRI of Multiple Sclerosis showed multiple high intensity areas in the White Matter of the Cerebrum and Cerebellum, Capsula Interna, and Crus Cerebri, etc.

Most of these lesions were clinically silent, being characteristic of MS.

In two MS cases, however, initial MRI revealed no abnormal findings. Thus, the diagnosis of MS can not be made by initial MRI only.

Objective
To assess the temporal relations among Retinal appearance, disruption of the Blood-Retinal Barrier, clinical subgroup, disease course, and disruption of the Blood-Brain Barrier in Multiple Sclerosis.

Design
A 6-month prospective study involving monthly clinical Ocular Examinations, Color Fundus Photography, Fundus Fluorescein Angiograms.

And Magnetic Resonance Brain Scans with Gadolinium-Diethylenetriamine-Pentaacetic Acid (Gd-DPTA) enhancement.

Setting & Patients
University-based Ophthalmology and Neurology departments. Twenty-three patients with Relapsing/Remitting, Primary/Progressive, or Secondary/Progressive Multiple Sclerosis.

Results
Retinal venous sheathing was seen in six patients.

The appearances observed included focal Venous sheathing, diffuse Venous sheathing, sheathing centered on sites of ArterioVenous crossover, and focal PeriVenous hemorrhage.

Arteriolar sheathing was also observed in one patient. Venous leakage on Fundus Fluorescein Angiogram was detected in three patients, all of whom also had sheathing.

The following three patterns of disruption of the Blood-Retinal Barrier were seen on Fundus Fluorescein Angiogram:
1. Focal leakage
2. Extensive leakage
3. Very late wall staining

In one patient, the leakage was transitory.

No correlations were observed between Ophthalmologic features and Multiple Sclerosis clinical subgroup, disease course, or the number of new (Gd-DTPA-enhancing) lesions on Magnetic Resonance Imaging.

Conclusions
Disruption of the Blood-Retinal Barrier, like the more frequent disruption of the Blood-Brain Barrier.

Seen on Magnetic Resonance Imaging, is often unrelated to clinical Neurologic relapses and occurs with apparently similar frequency in different patients independent of clinical disease course.

Patient
A 44-year-old woman has a history of Multiple Sclerosis since 20 years. Besides recurrent numbness she had many instances of Optic Nerve Neuritis which has led to a pronounced Optic Atrophy on her left eye.

Additionally, she has developed recurrent Iridocyclitis on her right eye. This was the reason why she was referred to our outpatient department for evaluation.

Ophthalmic Examination revealed an Iridocyclitis associated with a multifocal Retinal Periphlebitis and severe Cystoid Macular Edema in her right eye.

Conclusion
Patients with Multiple Sclerosis develop in approximately 30% of cases Retinal Periphlebitis which may rarely be associated with Anterior Uveitis or Cystoid Macular Edema as observed in our patient.

Methods
From January to December 2001, 89 patients with Multiple Sclerosis (MS) were treated in our hospital; 24 of them were diagnosed for the first time.

All patients underwent a complete Ophthalmologic examination including a three-mirror contact lens examination when Photopsias were found or the disease was diagnosed primarily.

Results
Two patients showed VitreoRetinal Tractions with signs of periphlebitis before clinical-neurological manifestation of Multiple Sclerosis.

The third patient, in whom the disease had been known for years, showed distinct NeoVascularizations, Vasculitis, and recurrent Vitreous Hemorrhages.

High-dose steroid therapy resulted in stabilization of the Retinal situation in one patient, but the Tractions remained unchanged.

Additional laser coagulation in the second patient achieved stabilization and reduction of the Tractions. A Pars Plana Vitrectomy led to stabilization of the Retinal proliferation in the third patient.

Conclusions
The VitreoRetinal Traction syndrome is associated with MS and can precede its clinical-Neurological manifestation.

The good results after argon laser coagulation and VitreoRetinal surgery suggest a Vascular pathogenesis of these Tractions.

Background
Although the role of Vascular pathology in Multiple Sclerosis (MS) lesions was suggested long ago, the derivation of these lesions from the Vasculature has been difficult to assess in vivo.

UltraHigh-field (eg, 7-T [Tesla]) Magnetic Resonance Imaging (MRI) has become a tool for assessing Vascular involvement in MS lesions owing to markedly increased image resolution and susceptibility contrast of Venous blood.

Objective
To describe the PeriVenous association of MS Lesions on high-resolution and high-contrast 7-T susceptibility-sensitive MRI.

Design, Setting & Patients
Case study, University hospital. Two women with clinically definite Relapsing/Remitting MS.

Results
We demonstrated markedly enhanced detection of unique MicroVascular involvement associated with most of the visualized MS lesions with abnormal signals on and around the Venous Wall on 7-T compared with 3-T MRI.

Conclusions
These findings, which have never been shown on conventional fields of MRI, not only allow for direct evidence of Vascular pathogenesis in MS in vivo.

But, also have important implications for monitoring lesion activity and therapeutic response.