Neurotrophic KeratopathyOSDNCT07694817
Clinical Predictors of Visual Outcome in Patients Affected With Ocular Surface Diseases
An observational study of Neurotrophic Keratopathy and Exposure Keratopathy, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
This retrospective-prospective study aims to identify the diagnostic parameters most predictive of BSCVA in patients with OSD. Clinical, structural, and biochemical data will be collected from standard-of-care examinations and patient-reported outcome questionnaires. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neurotrophic Keratopathy, Exposure Keratopathy, Limbal Stem Cell Deficiency (LSCD)
- How many people
- 1,000 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2026to Dec 2029
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study will enroll adult patients (≥18 years old) of both sexes, representative of the population affected by OSD. No restrictions will be applied regarding ethnicity or socioeconomic background
Who may be able to join
- The participant is willing and able to provide written informed consent for study participation (prospective cohort).
- Adult participants aged ≥18 years at the time of inclusion.
- Clinically confirmed diagnosis of OSD, including but not limited to inflammatory keratopathies, neurotrophic keratopathy, exposure keratopathy, limbal stem cell deficiency, post-surgical or post-traumatic corneal alterations.
- Measurable BSCVA obtained through standardized manifest refraction and ETDRS chart testing at baseline.
- Available dataset for the diagnostic tests required by the study (e.g., corneal topography, pachymetry, confocal microscopy, corneal sensitivity testing, slit-lamp imaging, tear cytokine analysis, impression cytology).
- Willingness and ability to attend follow-up visits and complete all study-related procedures according to the study schedule.
Who cannot join
- Change of retinal, optic nerve, or macular pathology that may affect best spectacle-corrected visual acuity independently of the cornea or ocular surface (e.g., age-related macular degeneration, diabetic macular edema, optic neuropathy) in the period of study
- History of intraocular or corneal surgery within 3 months prior to baseline evaluation.
- Active intraocular inflammation, glaucoma with uncontrolled intraocular pressure, or corneal conditions not compatible with accurate imaging or measurement (e.g., severe scarring, leukoma).
- Uncontrolled systemic diseases that may impair vision or corneal health (e.g., advanced diabetes, autoimmune disease in active phase).
- Inability or unwillingness to attend follow-up visits or complete study assessments.
- Pregnant or breastfeeding women will not be enrolled, as hormonal fluctuations can alter tear film and ocular surface physiology
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
IRCCS San Raffaele Scientific Institute
Milan, 20132
Giulio Ferrari, MD, PhD, Professor, +390226436186, ferrari.giulio@hsr.it
About this study
Official title: Clinical Predictors of Visual Outcome in Patients Affected With Ocular Surface Diseases: Single Center Retrospective-prospective Clinical Study
This retrospective-prospective study aims to identify the diagnostic parameters most predictive of BSCVA in patients with OSD. Clinical, structural, and biochemical data will be collected from standard-of-care examinations and patient-reported outcome questionnaires. The goal is to determine the most informative biomarkers for visual prognosis, streamline diagnostic workflows, and support individualized management of OSD.
Read the detailed description
The study is based on the hypothesis that specific diagnostic parameters, reflecting corneal structure, ocular surface (including corneal nerve) integrity, inflammatory activity and patients' reported outcomes (questionnaires), can reliably predict BSCVA in patients with OSD. Identifying these predictors will enable evidence-based selection of diagnostic tests, streamline clinical workflows, and improve patient care efficiency.
This is a monocentric, national, retrospective-prospective, observational cohort study.
The design includes two complementary phases:
- Retrospective cohort (n = 1,500): existing clinical records will be reviewed to extract standardized diagnostic and visual acuity data.
- Prospective cohort (n = 1,000): newly enrolled patients will undergo a standardized diagnostic protocol and follow-up vists at defined time points.
No experimental interventions or off-label diagnostic procedures are included; all assessments correspond to standard-of-care examinations.
Overall study duration: Approximately 60 months. Retrospective phase: a cohort of 1,500 patients will be selected among those patients who have been visited at the Cornea Clinic of the OSR in the last 20 years (starting from 01 Jan 2005 to 31 dec 2025) and who have a follow up of at least 12 months. Prospective phase: the investigators will enroll a cohort of 1,000 patients who will be rectruited among those visited at the Cornea Clinic of the OSR and who will be followed up for minimum 12 months. Recruitment will be ongoing for 48 months and the last patient will exit the study by month 60.
Individual patient duration: up to 12 months (baseline, 6-, and 12- month visits).
Interim analyses are planned at multiple time points throughout the study, contingent on data availability and sample size progression. The precise timing of these analyses will be determined based on the pace of data collection and event occurrence, rather than fixed calendar dates.
All data will be collected using standardized, validated diagnostic methods:
- Corneal topography (maximum keratometry, Kmax) and pachymetry
- In vivo confocal microscopy (corneal nerve density and cellular morphology)
- Slit-lamp photography (conjunctival hyperemia and corneal opacity grading)
- Cochet-Bonnet esthesiometer (corneal sensitivity)
- Goldmann applanation tonometry (intraocular pressure)
- Tear cytokine quantification (including IL-1β, IL-6, TNF-α, MMP-9, multiplex immunoassay)
- Impression cytology (inflammatory cell counts)
- Ocular pain/quality of life questionnaire scores (OSDI, OPAS, VAS, VFQ25, SPEED)
Retrospective data will be extracted from electronic medical records, while prospective data will be entered into a dedicated electronic case report form (eCRF) using harmonized acquisition protocols.
- Conditions
- Neurotrophic Keratopathy, Exposure Keratopathy, Limbal Stem Cell Deficiency (LSCD), Cornea Abnormality, Cornea Disease, Cornea Inflamed
- Medical subject headings
- Limbal Stem Cell Deficiency, Corneal Diseases, Keratitis
What is being measured
The primary outcome is the main question the study is designed to answer.
Best spectacle-corrected visual acuity (BSCVA) measured in logMAR
Best spectacle-corrected visual acuity will be measured using a standardized Early Treatment Diabetic Retinopathy Study chart at 4 meters after manifest refraction and best spectacle correction. Visual acuity will be reported as logarithm of the minimum angle of resolution. Expected range: -0.3 to 2.0 logMAR. Higher logMAR values indicate worse visual acuity.
Measured: Baseline, 6, and 12 months
Secondary outcomes (15)
Maximum keratometry (K max) measured by corneal tomography
Maximum keratometry will be measured by corneal tomography. Unit of Measure is Diopters (D). Higher values indicate greater corneal steepening.
Measured: Baseline, 6, and 12 months
Central corneal thickness (CCT) measured by corneal tomography
Central corneal thickness will be measured by corneal tomography. Unit of Measure is micrometers (µm). Lower values indicate greater corneal thinning.
Measured: Baseline, 6, and 12 months
Corneal nerve density measured by in vivo confocal microscopy
Corneal nerve density will be measured using in vivo confocal microscopy. Unit of Measure is fibers/mm². Higher values indicate greater corneal nerve density.
Measured: Baseline, 6, and 12 months
Corneal sensitivity measured by Cochet-Bonnet esthesiometer
Corneal sensitivity will be measured using the Cochet-Bonnet esthesiometer and reported as filament length. Unit of Measure is millimeter (mm). Higher values indicate better corneal sensitivity.
Measured: Baseline, 6, and 12 months
Tear fluid interleukin-1 beta (IL-1β) concentration
Interleukin-1 beta concentration will be measured in tear fluid samples by tear film analysis. Unit of Measure is pg/mL. Higher values indicate greater inflammatory activity.
Measured: Baseline, 6, and 12 months
Tear fluid interleukin-6 (IL-6) concentration
Interleukin-6 concentration will be measured in tear fluid samples by tear film analysis. Unit of Measure is pg/mL. Higher values indicate greater inflammatory activity.
Measured: Baseline, 6, and 12 months
Tear fluid tumor necrosis factor-alpha (TNF-α) concentration
Tumor necrosis factor-alpha concentration will be measured in tear fluid samples by tear film analysis. Unit of Measure is pg/mL. Higher values indicate greater inflammatory activity.
Measured: Baseline, 6, and 12 months
Tear fluid matrix metalloproteinase-9 (MMP-9) concentration
Matrix metalloproteinase-9 concentration will be measured in tear fluid samples by tear film analysis. Unit of Measure is ng/mL. Higher values indicate greater inflammatory activity.
Measured: Baseline, 6, and 12 months
Inflammatory cell count measured by impression cytology
Inflammatory cell count will be measured using impression cytology of the ocular surface. Unit of Measure is cells/mm². Higher values indicate greater ocular surface inflammation.
Measured: Baseline, 6, and 12 months
Intraocular pressure (IOP) measured by Goldmann applanation tonometry
Intraocular pressure will be measured using Goldmann applanation tonometry. Unit of Measure in mmHg. Higher values indicate higher intraocular pressure.
Measured: Baseline, 6, and 12 months
Ocular Surface Disease Index (OSDI) score
Ocular surface symptoms and vision-related function will be assessed using the Ocular Surface Disease Index questionnaire. The total score ranges from 0 to 100, with higher scores indicating more severe ocular surface disease symptoms.
Measured: Baseline, 6, and 12 months
Ocular Pain Assessment Survey (OPAS) quality-of-life interference score
Pain-related interference with quality of life will be assessed using the Ocular Pain Assessment Survey quality-of-life interference score. The score ranges from 0 to 10, where 0 indicates no interference with quality of life and 10 indicates maximum interference with quality of life. Higher scores indicate worse pain-related quality-of-life impairment.
Measured: Baseline, 6, and 12 months
Visual Analog Scale (VAS) pain score
Ocular pain will be assessed using a Visual Analog Scale. The score ranges from 0 to 10, where 0 indicates no ocular pain and 10 indicates the worst imaginable ocular pain. Higher scores indicate worse ocular pain.
Measured: Baseline, 6, and 12 months
National Eye Institute Visual Function Questionnaire-25 (VFQ-25) composite score
Vision-related quality of life will be assessed using the National Eye Institute Visual Function Questionnaire-25. The composite score ranges from 0 to 100, where 0 indicates the worst possible vision-related quality of life and 100 indicates the best possible vision-related quality of life. Higher scores indicate better vision-related quality of life.
Measured: Baseline, 6, and 12 months
Standard Patient Evaluation of Eye Dryness (SPEED) score
Dry eye symptoms will be assessed using the Standard Patient Evaluation of Eye Dryness questionnaire. The total score ranges from 0 to 28, where 0 indicates no dry eye symptoms and 28 indicates the most severe dry eye symptoms. Higher scores indicate worse dry eye symptoms.
Measured: Baseline, 6, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2026
- Study startJul 2026 (estimated)
- Primary completionDec 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurotrophic KeratopathyStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- 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 only
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giulio Ferrari, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07694817
- Sponsor's protocol ID
- OSD
- Acronym
- OSD
- Status last verified
- Jul 2026
- First submitted
- 23 Jun 2026
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Predictors of Visual Outcome in Patients Affected With Ocular Surface Diseases: Single Center Retrospective-prospective Clinical Study
- ClinicalTrials.gov ID
- NCT07694817
- Acronym / sponsor ID
- OSD / OSD
- Conditions
- Neurotrophic Keratopathy, Exposure Keratopathy, Limbal Stem Cell Deficiency (LSCD), Cornea Abnormality, Cornea Disease, Cornea Inflamed
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- Jul 2026 (estimated)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 10 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.
This retrospective-prospective study aims to identify the diagnostic parameters most predictive of BSCVA in patients with OSD. Clinical, structural, and biochemical data will be collected from standard-of-care examinations and patient-reported outcome questionnaires. The goal is to determine the most informative biomarkers for visual prognosis, streamline diagnostic workflows, and support individualized management of OSD.
Detailed description
The study is based on the hypothesis that specific diagnostic parameters, reflecting corneal structure, ocular surface (including corneal nerve) integrity, inflammatory activity and patients' reported outcomes (questionnaires), can reliably predict BSCVA in patients with OSD. Identifying these predictors will enable evidence-based selection of diagnostic tests, streamline clinical workflows, and improve patient care efficiency.
This is a monocentric, national, retrospective-prospective, observational cohort study.
The design includes two complementary phases:
- Retrospective cohort (n = 1,500): existing clinical records will be reviewed to extract standardized diagnostic and visual acuity data.
- Prospective cohort (n = 1,000): newly enrolled patients will undergo a standardized diagnostic protocol and follow-up vists at defined time points.
No experimental interventions or off-label diagnostic procedures are included; all assessments correspond to standard-of-care examinations.
Overall study duration: Approximately 60 months. Retrospective phase: a cohort of 1,500 patients will be selected among those patients who have been visited at the Cornea Clinic of the OSR in the last 20 years (starting from 01 Jan 2005 to 31 dec 2025) and who have a follow up of at least 12 months. Prospective phase: the investigators will enroll a cohort of 1,000 patients who will be rectruited among those visited at the Cornea Clinic of the OSR and who will be followed up for minimum 12 months. Recruitment will be ongoing for 48 months and the last patient will exit the study by month 60.
Individual patient duration: up to 12 months (baseline, 6-, and 12- month visits).
Interim analyses are planned at multiple time points throughout the study, contingent on data availability and sample size progression. The precise timing of these analyses will be determined based on the pace of data collection and event occurrence, rather than fixed calendar dates.
All data will be collected using standardized, validated diagnostic methods:
- Corneal topography (maximum keratometry, Kmax) and pachymetry
- In vivo confocal microscopy (corneal nerve density and cellular morphology)
- Slit-lamp photography (conjunctival hyperemia and corneal opacity grading)
- Cochet-Bonnet esthesiometer (corneal sensitivity)
- Goldmann applanation tonometry (intraocular pressure)
- Tear cytokine quantification (including IL-1β, IL-6, TNF-α, MMP-9, multiplex immunoassay)
- Impression cytology (inflammatory cell counts)
- Ocular pain/quality of life questionnaire scores (OSDI, OPAS, VAS, VFQ25, SPEED)
Retrospective data will be extracted from electronic medical records, while prospective data will be entered into a dedicated electronic case report form (eCRF) using harmonized acquisition protocols.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study will enroll adult patients (≥18 years old) of both sexes, representative of the population affected by OSD. No restrictions will be applied regarding ethnicity or socioeconomic background
Key inclusion criteria (6 listed)
- The participant is willing and able to provide written informed consent for study participation (prospective cohort).
- Adult participants aged ≥18 years at the time of inclusion.
- Clinically confirmed diagnosis of OSD, including but not limited to inflammatory keratopathies, neurotrophic keratopathy, exposure keratopathy, limbal stem cell deficiency, post-surgical or post-traumatic corneal alterations.
- Measurable BSCVA obtained through standardized manifest refraction and ETDRS chart testing at baseline.
- Available dataset for the diagnostic tests required by the study (e.g., corneal topography, pachymetry, confocal microscopy, corneal sensitivity testing, slit-lamp imaging, tear cytokine analysis, impression cytology).
Key exclusion criteria (6 listed)
- Change of retinal, optic nerve, or macular pathology that may affect best spectacle-corrected visual acuity independently of the cornea or ocular surface (e.g., age-related macular degeneration, diabetic macular edema, optic neuropathy) in the period of study
- History of intraocular or corneal surgery within 3 months prior to baseline evaluation.
- Active intraocular inflammation, glaucoma with uncontrolled intraocular pressure, or corneal conditions not compatible with accurate imaging or measurement (e.g., severe scarring, leukoma).
- Uncontrolled systemic diseases that may impair vision or corneal health (e.g., advanced diabetes, autoimmune disease in active phase).
- Inability or unwillingness to attend follow-up visits or complete study assessments.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Best spectacle-corrected visual acuity (BSCVA) measured in logMAR
Time frame: Baseline, 6, and 12 months
Best spectacle-corrected visual acuity will be measured using a standardized Early Treatment Diabetic Retinopathy Study chart at 4 meters after manifest refraction and best spectacle correction. Visual acuity will be reported as logarithm of the minimum angle of resolution. Expected range: -0.3 to 2.0 logMAR. Higher logMAR values indicate worse visual acuity.
15 secondary outcomes
Maximum keratometry (K max) measured by corneal tomography
Time frame: Baseline, 6, and 12 months
Central corneal thickness (CCT) measured by corneal tomography
Time frame: Baseline, 6, and 12 months
Corneal nerve density measured by in vivo confocal microscopy
Time frame: Baseline, 6, and 12 months
Corneal sensitivity measured by Cochet-Bonnet esthesiometer
Time frame: Baseline, 6, and 12 months
Tear fluid interleukin-1 beta (IL-1β) concentration
Time frame: Baseline, 6, and 12 months
Tear fluid interleukin-6 (IL-6) concentration
Time frame: Baseline, 6, and 12 months
Tear fluid tumor necrosis factor-alpha (TNF-α) concentration
Time frame: Baseline, 6, and 12 months
Tear fluid matrix metalloproteinase-9 (MMP-9) concentration
Time frame: Baseline, 6, and 12 months
Inflammatory cell count measured by impression cytology
Time frame: Baseline, 6, and 12 months
Intraocular pressure (IOP) measured by Goldmann applanation tonometry
Time frame: Baseline, 6, and 12 months
Ocular Surface Disease Index (OSDI) score
Time frame: Baseline, 6, and 12 months
Ocular Pain Assessment Survey (OPAS) quality-of-life interference score
Time frame: Baseline, 6, and 12 months
Visual Analog Scale (VAS) pain score
Time frame: Baseline, 6, and 12 months
National Eye Institute Visual Function Questionnaire-25 (VFQ-25) composite score
Time frame: Baseline, 6, and 12 months
Standard Patient Evaluation of Eye Dryness (SPEED) score
Time frame: Baseline, 6, and 12 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 14 Jul 2026.
- Individual participant dataSharing planned: No
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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.
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 Neurotrophic Keratopathy and Exposure Keratopathy, 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 6 inclusion and 6 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: opening soon, as of the sponsor's last update on 14 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 Giulio Ferrari, MD, PhD, Professor (+390226436186, ferrari.giulio@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best spectacle-corrected visual acuity (BSCVA) measured in logMAR (time frame: Baseline, 6, and 12 months). 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 14 Jul 2026.