An observational study in Multiple Sclerosis, Alzheimer Disease and Parkinson Disease, sponsored by IRCCS San Raffaele. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-22.
Sponsored by IRCCS San Raffaele · Observational
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.
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).
3,264 studies on the registry are indexed under Multiple Sclerosis; 659 are open to participants now.
This study's planned enrollment of 1,050 is above the median of 100 across 970 observational studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →IRCCS San Raffaele is the lead sponsor of 453 studies on the registry; 234 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adult patients with a diagnosis of a Central Nervous System neurological disease (Multiple Sclerosis; Alzheimer's disease; Parkinson's disease; migraine/headache) recruited from the neurology outpatient clinics and inpatient wards of IRCCS San Raffaele Hospital, Milan, Italy. Healthy controls recruited primarily from medical students, colleagues, and relatives of patients.
Inclusion Criteria for neurological patients:
Inclusion Criteria for healthy controls:
Exclusion Criteria for neurological patients:
Exclusion Criteria for healthy controls:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
210 patients with a diagnosis of Multiple Sclerosis according to current diagnostic criteria, stratified into three age subgroups (20-40, 40-60, and over 60 years, 70 per subgroup). Undergo OCT at baseline and follow-up visits at 6, 12, 18, and/or 24 months, alongside standard clinical assessments including EDSS.
Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT
210 patients with a diagnosis of Alzheimer's disease according to current diagnostic criteria, stratified into three age subgroups (70 per subgroup). Undergo OCT at baseline and follow-up visits alongside standard neuropsychological assessments, brain MRI, PET, and CSF biomarkers as part of routine clinical care.
Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT
210 patients with a diagnosis of Parkinson's disease according to current diagnostic criteria, stratified into three age subgroups (70 per subgroup). Undergo OCT at baseline and follow-up visits alongside standard clinical assessments including UPDRS.
Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT
210 patients with a diagnosis of migraine or headache according to current diagnostic criteria, stratified into three age subgroups (70 per subgroup). Undergo OCT at baseline and follow-up visits alongside standard clinical assessments.
Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT
210 healthy subjects without neurological disease, age-matched to patients, stratified into three age subgroups (20-40, 40-60, and over 60 years, 70 per subgroup). Recruited primarily from medical students, colleagues, and relatives of patients. Undergo OCT at baseline and follow-up visits.
Device: 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 automated measurements of the thickness of individual retinal layers. OCT is performed at baseline and at follow-up visits at 6, 12, 18, and/or 24 months. Ophthalmological evaluation may be performed at the investigators' discretion if OCT images, clinical symptoms, or medical history suggest concurrent ocular pathology. Patients with a known diagnosis of epilepsy or history of epileptic seizures will not undergo specific imaging modes using clearly visible light sources (MultiColor, FA, BAF).
Annual rate of peripapillary RNFL thinning in patients with Multiple Sclerosis vs healthy controls
Annualized thinning rate (micrometers per year) of the peripapillary retinal nerve fiber layer (RNFL) measured by OCT in patients with Multiple Sclerosis compared to age-matched healthy controls.
Time frame: Baseline, 6, 12, 18, and 24 months
Annual rate of peripapillary RNFL thinning in patients with Alzheimer's Disease vs healthy controls
Annualized thinning rate (micrometers per year) of the peripapillary retinal nerve fiber layer (RNFL) measured by OCT in patients with Alzheimer's Disease compared to age-matched healthy controls.
Time frame: Baseline, 6, 12, 18, and 24 months
Annual rate of peripapillary RNFL thinning in patients with Parkinson's Disease vs healthy controls
Annualized thinning rate (micrometers per year) of the peripapillary retinal nerve fiber layer (RNFL) measured by OCT in patients with Parkinson's Disease compared to age-matched healthy controls.
Time frame: Baseline, 6, 12, 18, and 24 months
Annual rate of macular GCL thinning in patients with Multiple Sclerosis disease vs healthy controls
Annualized thinning rate (micrometers per year) of the macular ganglion cell layer (GCL) measured by OCT in patients with Multiple Sclerosis compared to age-matched healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
Annual rate of macular GCL thinning in patients with Alzheimer's Disease vs healthy controls
Annualized thinning rate (micrometers per year) of the macular ganglion cell layer (GCL) measured by OCT in patients with Alzheimer's Disease compared to age-matched healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
Annual rate of macular GCL thinning in patients with Parkinson's Disease vs healthy controls
Annualized thinning rate (micrometers per year) of the macular ganglion cell layer (GCL) measured by OCT in patients with Parkinson's Disease compared to age-matched healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
Annual rate of macular IPL thinning in patients with Multiple Sclerosis vs healthy controls
Annualized thinning rate (micrometers per year) of the macular inner plexiform layer (IPL) measured by OCT in patients with Multiple Sclerosis compared to age-matched healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
Annual rate of macular IPL thinning in patients with Alzheimer's Disease vs healthy controls
Annualized thinning rate (micrometers per year) of the macular inner plexiform layer (IPL) measured by OCT in patients with Alzheimer's Disease compared to age-matched healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
Annual rate of macular IPL thinning in patients with Parkinson's Disease vs healthy controls
Annualized thinning rate (micrometers per year) of the macular inner plexiform layer (IPL) measured by OCT in patients with Parkinson's Disease compared to age-matched healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thinning rate and EDSS worsening in Multiple Sclerosis
Pearson or Spearman correlation between the annualized RNFL thinning rate measured by OCT and worsening on the Expanded Disability Status Scale (EDSS) in patients with Multiple Sclerosis.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thinning rate and EDSS worsening in Multiple Sclerosis
Pearson or Spearman correlation between the annualized GCL thinning rate measured by OCT and worsening on the Expanded Disability Status Scale (EDSS) in patients with Multiple Sclerosis.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thinning rate and EDSS worsening in Multiple Sclerosis
Pearson or Spearman correlation between the annualized IPL thinning rate measured by OCT and worsening on the Expanded Disability Status Scale (EDSS) in patients with Multiple Sclerosis.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thinning rate and UPDRS worsening in Parkinson's disease
Pearson or Spearman correlation between the annualized RNFL thinning rate measured by OCT and worsening on the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thinning rate and UPDRS worsening in Parkinson's disease
Pearson or Spearman correlation between the annualized GCL thinning rate measured by OCT and worsening on the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thinning rate and neuropsychological performance in Alzheimer's disease
Pearson or Spearman correlation between the annualized RNFL thinning rate measured by OCT and scores on comprehensive neuropsychological assessment in patients with Alzheimer's disease.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thinning rate and neuropsychological performance in Alzheimer's disease
Pearson or Spearman correlation between the annualized GCL thinning rate measured by OCT and scores on comprehensive neuropsychological assessment in patients with Alzheimer's disease.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thinning rate and neuropsychological performance in Alzheimer's disease
Pearson or Spearman correlation between the annualized IPL thinning rate measured by OCT and scores on comprehensive neuropsychological assessment in patients with Alzheimer's disease.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and brain MRI lesion load
Pearson or Spearman correlation between OCT-derived RNFL tickness and brain MRI parameters (lesion load) used in routine clinical practice for each neurological disease subgroup.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and brain MRI cortical atrophy
Pearson or Spearman correlation between OCT-derived RNFL tickness and brain MRI parameters (cortical atrophy) used in routine clinical practice for each neurological disease subgroup.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and brain MRI lesion load
Pearson or Spearman correlation between OCT-derived GCL tickness and brain MRI parameters (lesion load) used in routine clinical practice for each neurological disease subgroup.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and brain MRI cortical atrophy
Pearson or Spearman correlation between OCT-derived GCL tickness and brain MRI parameters (cortical atrophy) used in routine clinical practice for each neurological disease subgroup.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and brain MRI lesion load
Pearson or Spearman correlation between OCT-derived IPL tickness and brain MRI parameters (lesion load) used in routine clinical practice for each neurological disease subgroup.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and brain MRI cortical atrophy
Pearson or Spearman correlation between OCT-derived IPL tickness and brain MRI parameters (cortical atrophy) used in routine clinical practice for each neurological disease subgroup.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and PET findings
Pearson or Spearman correlation between OCT-derived RNFL thickness and brain PET parameters used in routine clinical practice for applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and PET findings
Pearson or Spearman correlation between OCT-derived GCL thickness and brain PET parameters used in routine clinical practice for applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and PET findings
Pearson or Spearman correlation between OCT-derived IPL thickness and brain PET parameters used in routine clinical practice for applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
24. Correlation between RNFL thickness and CSF biomarker (Abeta40)
Pearson or Spearman correlation between OCT-derived RNFL thickness and CSF biomarkers (Abeta40) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and CSF biomarker (Abeta40)
Pearson or Spearman correlation between OCT-derived GCL thickness and CSF biomarkers (Abeta40) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
orrelation between IPL thickness and CSF biomarker (Abeta40)
Pearson or Spearman correlation between OCT-derived IPL thickness and CSF biomarkers (Abeta40) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and CSF biomarker (Abeta42)
Pearson or Spearman correlation between OCT-derived RNFL thickness and CSF biomarkers (Abeta42) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and CSF biomarker (Abeta42)
Pearson or Spearman correlation between OCT-derived GCL thickness and CSF biomarkers (Abeta42) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and CSF biomarker (Abeta42)
Pearson or Spearman correlation between OCT-derived IPL thickness and CSF biomarkers (Abeta42) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and CSF biomarkers (pTAU)
Pearson or Spearman correlation between OCT-derived RNFL thickness and CSF biomarkers (pTAU) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and CSF biomarkers (pTAU)
Pearson or Spearman correlation between OCT-derived GCL thickness and CSF biomarkers (pTAU) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and CSF biomarkers (pTAU)
Pearson or Spearman correlation between OCT-derived IPL thickness and CSF biomarkers (pTAU) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and CSF biomarkers (NfL)
Pearson or Spearman correlation between OCT-derived RNFL thickness and CSF biomarkers (NfL) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and CSF biomarkers (NfL)
Pearson or Spearman correlation between OCT-derived GCL thickness and CSF biomarkers (NfL) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and CSF biomarkers (NfL)
Pearson or Spearman correlation between OCT-derived IPL thickness and CSF biomarkers (NfL) in applicable neurological disease subgroups.
Time frame: Baseline, 6, 12, 18, and 24 months
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Started Oct 2023 (actual). Primary completion is estimated for Apr 2030, 77 months after the start.
Of 334 non-industry observational studies under Multiple Sclerosis, half reached primary completion within 36 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 73. This study's planned 77 months is above that.
Counting every sponsor, half of 425 studies reached it within 41 months; a quarter within 15 and three quarters within 75.
How these figures are worked out, and which studies are left out of them.
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