Multiple SclerosisOCTNCT07720765
Optical Coherence Tomography in Neurological Practice: Utility and Applicability Across Neurological Diseases (OCt.IN.N)
An observational study of Multiple Sclerosis and Alzheimer Disease, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Alzheimer Disease, Parkinson Disease
- What is being tested?
- Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT
- Type of treatment
- Medical device
- How many people
- 1,050 participants
- Where
- 1 siteItaly
- Study dates
- 9 Oct 2023to 1 Apr 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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.
- 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.
Who cannot join
- 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.
- Refusal to participate or withdrawal of informed consent.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Roberto Santangelo, MD contact
Italy1 site, 1 recruiting
- Recruiting
IRCCS Ospedale San Raffaele - Neurology and Neurophysiology Unit
Milan, Milano, 20132
Federica Agosta, MD, 0226433051, agosta.federica@hsr.it
Roberto Santangelo, MD
About this study
Official title: A National, Monocentric, Prospective Cohort Study to Evaluate the Utility and Applicability of Optical Coherence Tomography in Neurological Clinical Practice
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.
Read the detailed description
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).
- Being tested
- Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT
- Keywords
- Optical Coherence Tomography, OCT, Retinal nerve fiber layer, RNFL, Ganglion cell layer, GCL, Multiple Sclerosis, Alzheimer's disease, Parkinson's disease, Migraine, Neurodegeneration, Neuro-retina, Biomarker
- Medical subject headings
- Multiple Sclerosis, Alzheimer Disease, Parkinson Disease, Migraine Disorders, Headache Disorders, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCTDevice
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).
| Study group | Role | What they receive |
|---|---|---|
| Multiple Sclerosis patients | 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. Receives: Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT | |
| Alzheimer's disease patients | 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. Receives: Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT | |
| Parkinson's disease patients | 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. Receives: Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT | |
| Migraine and headache patients | 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. Receives: Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT | |
| Healthy Controls | 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. Receives: Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline, 6, 12, 18, and 24 months
Secondary outcomes (29)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 6, 12, 18, and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2026
- Study start9 Oct 2023
- Primary completion1 Apr 2030 (estimated)
- Study completion1 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 1,050 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Massimo Filippi, IRCCS San Raffaele
- Investigators
- Massimo Filippi, Prof, MD, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07720765
- Sponsor's protocol ID
- OCtINN
- Acronym
- OCT
- Status last verified
- Jul 2026
- First submitted
- 17 Jul 2026
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A National, Monocentric, Prospective Cohort Study to Evaluate the Utility and Applicability of Optical Coherence Tomography in Neurological Clinical Practice
- ClinicalTrials.gov ID
- NCT07720765
- Acronym / sponsor ID
- OCT / OCtINN
- Keywords
- Optical Coherence Tomography, OCT, Retinal nerve fiber layer, RNFL, Ganglion cell layer, GCL, Multiple Sclerosis, Alzheimer's disease
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,050 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 9 Oct 2023 (actual)
- Primary completion
- 1 Apr 2030 (estimated)
- Study completion
- 1 Apr 2031 (estimated)
- First posted
- 22 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Multiple Sclerosis patients | – | Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT210 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. |
| Alzheimer's disease patients | – | Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT210 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. |
| Parkinson's disease patients | – | Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT210 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. |
| Migraine and headache patients | – | Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT210 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. |
| Healthy Controls | – | Device: Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCT210 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (8 listed)
- 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.
- Absence of neurological disease.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Optical Coherence Tomography (OCT) - Heidelberg SPECTRALIS HRA+OCTSpectral-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). | Device | Alzheimer's disease patients, Healthy Controls, Migraine and headache patients, Multiple Sclerosis patients, Parkinson's disease patients |
Primary outcome
Annual rate of peripapillary RNFL thinning in patients with Multiple Sclerosis vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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.
Annual rate of peripapillary RNFL thinning in patients with Alzheimer's Disease vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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.
Annual rate of peripapillary RNFL thinning in patients with Parkinson's Disease vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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.
Annual rate of macular GCL thinning in patients with Multiple Sclerosis disease vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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
Annual rate of macular GCL thinning in patients with Alzheimer's Disease vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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
Annual rate of macular GCL thinning in patients with Parkinson's Disease vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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
Annual rate of macular IPL thinning in patients with Multiple Sclerosis vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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
Annual rate of macular IPL thinning in patients with Alzheimer's Disease vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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
Annual rate of macular IPL thinning in patients with Parkinson's Disease vs healthy controls
Time frame: Baseline, 6, 12, 18, and 24 months
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
29 secondary outcomes
Correlation between RNFL thinning rate and EDSS worsening in Multiple Sclerosis
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thinning rate and EDSS worsening in Multiple Sclerosis
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thinning rate and EDSS worsening in Multiple Sclerosis
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thinning rate and UPDRS worsening in Parkinson's disease
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thinning rate and UPDRS worsening in Parkinson's disease
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thinning rate and neuropsychological performance in Alzheimer's disease
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thinning rate and neuropsychological performance in Alzheimer's disease
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thinning rate and neuropsychological performance in Alzheimer's disease
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and brain MRI lesion load
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and brain MRI cortical atrophy
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and brain MRI lesion load
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and brain MRI cortical atrophy
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and brain MRI lesion load
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and brain MRI cortical atrophy
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and PET findings
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and PET findings
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and PET findings
Time frame: Baseline, 6, 12, 18, and 24 months
24. Correlation between RNFL thickness and CSF biomarker (Abeta40)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and CSF biomarker (Abeta40)
Time frame: Baseline, 6, 12, 18, and 24 months
orrelation between IPL thickness and CSF biomarker (Abeta40)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and CSF biomarker (Abeta42)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and CSF biomarker (Abeta42)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and CSF biomarker (Abeta42)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and CSF biomarkers (pTAU)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and CSF biomarkers (pTAU)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and CSF biomarkers (pTAU)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between RNFL thickness and CSF biomarkers (NfL)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between GCL thickness and CSF biomarkers (NfL)
Time frame: Baseline, 6, 12, 18, and 24 months
Correlation between IPL thickness and CSF biomarkers (NfL)
Time frame: Baseline, 6, 12, 18, and 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Multiple Sclerosis
Active, not recruitingPhase 3
An Extension Study of Ublituximab in Participants With Relapsing Multiple Sclerosis
Relapsing Multiple Sclerosis (RMS)
RecruitingObservational study
A Study Evaluating the Real World Experience of Participants Treated With BRIUMVI® (Ublituximab-xiiy) for Relapsing Multiple Sclerosis (RMS)
Relapsing Multiple Sclerosis, Multiple Sclerosis
RecruitingObservational study
Non-interventional Study of Subcutaneous Ocrelizumab in Persons With Relapsing-Remitting Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
RecruitingPhase 2
A Phase 2a Study of SUN-627 in Participants With Non-Active Secondary Progressive and Primary Progressive Multiple Sclerosis (SPMS/PPMS)
Primary Progressive Multiple Sclerosis, Primary Progressive MS
RecruitingPhase 4
A Study of Ocrelizumab Administered Subcutaneously in Participants With Multiple Sclerosis Who Switch From an Approved Anti-CD20 Therapy
Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Roberto Santangelo, MD contact
Massimo Filippi, Prof, MD principal investigator
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis and Alzheimer Disease, run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Federica Agosta, MD (0226433051, agosta.federica@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annual rate of peripapillary RNFL thinning in patients with Multiple Sclerosis vs healthy controls (time frame: Baseline, 6, 12, 18, and 24 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.