Optical Coherence Tomography in Neurological Practice: Utility and Applicability Across Neurological Diseases (OCt.IN.N)

Официальное название

A National, Monocentric, Prospective Cohort Study to Evaluate the Utility and Applicability of Optical Coherence Tomography in Neurological Clinical Practice

Обзор

OCt.IN.N is a national, monocentric, prospective, observational cohort study evaluating the utility and applicability of Optical Coherence Tomography (OCT) in the diagnostic workup and longitudinal monitoring of neurological diseases. 840 patients with Central Nervous System neurological diseases (Multiple Sclerosis, Alzheimer's disease, Parkinson's disease, migraine/headache) and 210 age-matched healthy controls will undergo OCT examination at baseline and at 6, 12, 18, and 24 months of follow-up at IRCCS San Raffaele Hospital, Milan, Italy. OCT is a non-invasive, rapid, and reproducible technique that automatically measures the thickness of individual retinal layers. Retinal layer thicknesses and their longitudinal changes will be correlated with established clinical scales, neuroimaging, and biological markers used in routine neurological practice.

Подробное описание

The retina and optic nerve share the same embryological origins as the central nervous system (CNS). Several neurological diseases - including Multiple Sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD) - involve the visual system at both pre-chiasmatic (neuro-retina, optic nerve) and post-chiasmatic levels (optic tracts, optic radiations, primary visual cortex).

In MS, optic neuritis is one of the most frequent manifestations and can lead to optic nerve damage with retinal nerve fiber degeneration. In neurodegenerative diseases such as AD and PD, degeneration of retinal ganglion cells has been demonstrated. In AD, longitudinal observational studies have shown accelerated RNFL thinning over time compared to age-matched healthy controls, suggesting that neuro-retinal thinning in neurodegeneration reflects underlying neurodegenerative processes independent of normal aging.

Spectral-domain Optical Coherence Tomography (OCT) is a non-invasive, highly reproducible technique providing automated, high-resolution information on the thickness of individual retinal layers, including the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and the inner plexiform layer (IPL). OCT could represent a reliable, reproducible, and economically accessible tool for the diagnostic workup and monitoring of neurological diseases.

The device used is the Heidelberg SPECTRALIS HRA+OCT (Class IIa CE-marked medical device), operated according to the manufacturer's instructions and indications for use. The device is used according to its approved clinical indication for visualization of the posterior segment of the eye and retinal anatomy measurement.

Study design: monocentric, prospective, observational cohort study. Patients are recruited from the neurology outpatient clinics and inpatient wards of IRCCS San Raffaele Hospital. OCT is performed at baseline (T0) and at follow-up visits at 6, 12, 18, and/or 24 months. Ophthalmological evaluation may be requested at the investigators' discretion to exclude concurrent ocular pathology.

Three age subgroups are analyzed for all disease groups and controls: 20-40 years, 40-60 years, and over 60 years.

Statistical analyses include: descriptive statistics and ANOVA models (or non-parametric tests) for between-group comparisons at baseline; linear mixed-effects models for longitudinal changes over time; generalized estimating equations (GEE) when data from both eyes are considered; Pearson or Spearman correlation analyses between OCT measures and clinical, neuroimaging, and biological markers (EDSS for MS; UPDRS for PD; neuropsychological battery for AD; brain MRI, PET, and CSF biomarkers for migraine/headache).

Вмешательства

• Устройство Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT
  Spectral-domain Optical Coherence Tomography (OCT) performed using the Heidelberg SPECTRALIS HRA+OCT device (Class IIa CE-marked medical device). The procedure is non-invasive: the patient sits in front of the device and is asked to fix a target (light or cross) through a lens. No drugs or contrast agents are administered. OCT automatically acquires images of the macular region (where GCL and IPL are most represented) and the optic nerve head region (where RNFL is most represented), providing au

Первичные конечные точки

• Annual rate of peripapillary RNFL thinning in patients with Multiple Sclerosis vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Annual rate of peripapillary RNFL thinning in patients with Alzheimer's Disease vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Annual rate of peripapillary RNFL thinning in patients with Parkinson's Disease vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Annual rate of macular GCL thinning in patients with Multiple Sclerosis disease vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Annual rate of macular GCL thinning in patients with Alzheimer's Disease vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Annual rate of macular GCL thinning in patients with Parkinson's Disease vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Annual rate of macular IPL thinning in patients with Multiple Sclerosis vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Annual rate of macular IPL thinning in patients with Alzheimer's Disease vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Annual rate of macular IPL thinning in patients with Parkinson's Disease vs healthy controls [Срок оценки: Baseline, 6, 12, 18, and 24 months]

Вторичные конечные точки (12)

• Correlation between RNFL thinning rate and EDSS worsening in Multiple Sclerosis [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between GCL thinning rate and EDSS worsening in Multiple Sclerosis [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between IPL thinning rate and EDSS worsening in Multiple Sclerosis [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between RNFL thinning rate and UPDRS worsening in Parkinson's disease [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between GCL thinning rate and UPDRS worsening in Parkinson's disease [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between RNFL thinning rate and neuropsychological performance in Alzheimer's disease [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between GCL thinning rate and neuropsychological performance in Alzheimer's disease [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between IPL thinning rate and neuropsychological performance in Alzheimer's disease [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between RNFL thickness and brain MRI lesion load [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between RNFL thickness and brain MRI cortical atrophy [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between GCL thickness and brain MRI lesion load [Срок оценки: Baseline, 6, 12, 18, and 24 months]
• Correlation between GCL thickness and brain MRI cortical atrophy [Срок оценки: Baseline, 6, 12, 18, and 24 months]

Критерии участия

Inclusion Criteria for neurological patients:

• Diagnosis of a Central Nervous System neurological disease (inflammatory diseases such as Multiple Sclerosis; neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease; migraine/headache) according to currently accepted diagnostic criteria for each condition.
• Age greater than 18 years.
• Signed informed consent to study participation.
• Willingness and ability to undergo all study visits and procedures.

Inclusion Criteria for healthy controls:

• Absence of neurological disease.
• Age greater than 18 years.
• Signed informed consent to study participation.
• Willingness and ability to undergo all study visits and procedures.

Exclusion Criteria for neurological patients:

• Refusal to participate or withdrawal of informed consent.
• Known or confirmed ocular pathology identified during examination (ophthalmological evaluation may be requested at the investigators' discretion).
• Inability to understand instructions given by investigators.
• Presence of any condition that, in the investigators' opinion, renders the subject unsuitable for the study.
• For specific imaging modes using clearly visible light sources (MultiColor, FA, BAF): diagnosis of epilepsy or history of previous epileptic seizures.

Exclusion Criteria for healthy controls:

• Refusal to participate or withdrawal of informed consent.
• Known or confirmed ocular pathology identified during examination.
• Inability to understand instructions given by investigators.
• Presence of any condition that, in the investigators' opinion, renders the subject unsuitable for the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Италия · 1 центр

• IRCCS Ospedale San Raffaele - Neurology and Neurophysiology Unit — Milan

Идентификаторы

NCT: NCT07720765 · OCtINN

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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