Skip to main content
OpenTrials
Enrolling by Invitation

NCT Number: NCT07716930

Retinal OCT Changes and Biomarkers in Drug-Resistant Epilepsy

This prospective, longitudinal observational study investigates whether epilepsy involves a progressive neurodegenerative process. Retinal structural and microvascular changes assessed by optical coherence tomography (OCT) and optical coherence (OCTA) will be analyzed alongside inflammatory biomarkers (sCD14, sCD163, CCL2, IL-1β). The study aims to explore their association with epilepsy pathophysiology, clinical phenotype, prognosis, and drug-resistant epilepsy (DRE). Among participants with epilepsy, seizure severity and antiseizure medication-related adverse-effect burden will also be assessed longitudinally using the National Hospital Seizure Severity Scale (NHS3) and the Turkish version of Liverpool Adverse Events Profile (LAEP-TR).

Enrolling by Invitation

Interested in participating?

Request Info

Key information

Conditions

Epilepsy (treatment Refractory) Brain Diseases Central Nervous System Diseases Drug Resistant Epilepsy Epilepsy Inflammation Nerve Degeneration Nervous System Diseases Neuroinflammatory Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Neurology Clinic

Istanbul, 34668, Turkey (Türkiye)

About this study

Epilepsy may be associated with neuroinflammatory and neurodegenerative mechanisms. The retina provides a non-invasive window for evaluating neuroaxonal and microvascular changes through OCT and OCTA. This study will investigate whether retinal structural, microvascular, and serum inflammatory biomarker measures are associated with epilepsy phenotype, disease severity, prognosis, and drug-resistant epilepsy. Participants will be enrolled into three cohorts: adults with epilepsy, adults using antiseizure medications for non-epileptic indications, and healthy controls. Clinical data will include demographic characteristics, epilepsy history, mean monthly seizure frequency derived from seizure diaries and clinical records, antiseizure medication use, neurological examination findings, electroencephalography (EEG) findings, and magnetic resonance imaging (MRI) findings. Among participants with epilepsy, clinical epilepsy activity will be characterized using two prespecified components: mean monthly seizure frequency and seizure severity assessed with the National Hospital Seizure Severity Scale (NHS3). These components will be analyzed separately and jointly in multivariable models rather than combined into a study-specific unvalidated total score. The NHS3 will be administered at baseline and at 18 months based on the participant's most severe habitual seizure during the preceding 6 months. Patient-reported adverse effects associated with antiseizure medication treatment will be assessed separately at the same visits using the Turkish version of Liverpool Adverse Events Profile (LAEP-TR). All participants will undergo ophthalmological assessment, including visual acuity, intraocular pressure measurement, and refraction assessment. OCT and OCTA imaging will be used to measure peripapillary retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, inner nuclear layer thickness, macular volume, hyperreflective retinal foci, capillary density, and foveal avascular zone area.

Peripheral venous blood samples will be collected only from participants in the epilepsy group at baseline and at 18 months for serum biomarker analysis. Serum samples will be stored at -80°C. Serum soluble CD14, soluble CD163, C-C motif chemokine ligand 2, and interleukin-1 beta concentrations will be measured using commercial enzyme-linked immunosorbent assay kits according to the manufacturers' protocols. Serum biomarker outcomes and serum biomarker-based prediction analyses will therefore be restricted to participants with epilepsy.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age between 18 and 40 years
  • Ability to provide written informed consent
  • For the epilepsy group: diagnosis of epilepsy for at least 1 year
  • For the epilepsy group: treatment with at least one antiseizure medication for at least 1 year
  • For the disease-control group: diagnosis of migraine, analgesic-overuse headache, or neuralgia
  • For the disease-control group: current treatment with at least one antiseizure medication for a non-epileptic indication
  • For the disease-control group: no history of epilepsy or unprovoked seizures
  • For the healthy-control group: no history of epilepsy, major neurological disease, ophthalmological disease, or regular antiseizure medication use

Exclusion criteria

  • Age younger than 18 years or older than 40 years
  • Inability or unwillingness to provide written informed consent
  • History of ocular surgery, ocular trauma, glaucoma, retinal disease, optic neuropathy, or severe refractive error, defined as spherical equivalent greater than ±6.0 diopters
  • Media opacity or poor image quality preventing reliable OCT or OCTA assessment
  • Vigabatrin or Valproate use
  • Multiple sclerosis, Parkinson's disease, dementia, brain tumor, stroke, optic neuritis, or other major neurological disorders
  • Evidence of visual pathway lesions on MRI
  • Diabetes mellitus, uncontrolled hypertension, or other systemic vascular, metabolic diseases that may affect retinal or OCTA parameters
  • Chronic alcohol or psychoactive substance abuse
  • Inability to undergo OCT or OCTA examination because of cognitive, behavioral, or physical limitations

Treatment and study plan

Primary outcomes

  1. Annualized percentage change in peripapillary retinal nerve fiber layer thickness measured by OCT

    Time frame: Baseline to 18 months after enrollment.

    Peripapillary RNFL thickness will be assessed with Heidelberg OCT at baseline and 18 months using the optic nerve head-centered circular scan protocol. Eye-tracking and follow-up registration will ensure reproducibility. Automated segmentation will be reviewed for centration and accuracy; global and quadrant values (superior, inferior, nasal, temporal) will be recorded. Images will be checked for quality and artifacts; scans failing criteria or with uncorrectable errors will be repeated or excluded. For participants with two eligible eyes, mean thickness will be analyzed; if one eye is eligible, that measurement will be used. Annualized percentage change will be calculated as:

    [((18-month pRNFL thickness - baseline pRNFL thickness) / baseline pRNFL thickness) × 100] / 1.5 years.

    Unit of measure: Percent change per year

  2. Annualized percentage change in ganglion cell-inner plexiform layer thickness measured by OCT

    Time frame: Baseline to 18 months after enrollment

    Ganglion cell-inner plexiform layer (GC-IPL) thickness will be measured with Heidelberg OCT at baseline and 18 months using a fovea-centered 6 × 6 mm macular scan. Identical parameters and eye-tracking functions will ensure reproducibility. Automated segmentation will be reviewed for centration, accuracy, and artifacts; errors will be corrected when possible. GC-IPL thickness will be calculated as the sum of ganglion cell and inner plexiform layers. Scans failing quality criteria or with uncorrectable artifacts will be repeated or excluded. For two eligible eyes, mean thickness will be analyzed; if one eye is eligible, that measurement will be used. Annualized percentage change will be calculated as:

    {[(18-month GC-IPL thickness - baseline GC-IPL thickness) / baseline GC-IPL thickness] × 100} / 1.5 years.

    Unit of measure: Percent change per year

  3. Difference in annualized percentage change in peripapillary retinal nerve fiber layer thickness between drug-resistant and non-drug-resistant epilepsy groups

    Time frame: Baseline to 18 months after enrollment.

    Annualized percentage change in peripapillary retinal nerve fiber layer thickness measured by optical coherence tomography will be compared between participants with drug-resistant epilepsy and participants without drug-resistant epilepsy. This analysis will be performed only among participants with epilepsy.

    Drug-resistant epilepsy will be defined as failure of adequate trials of two tolerated, appropriately chosen and used antiseizure medication schedules to achieve sustained seizure freedom.

    Unit of measure: Percent change per year

  4. Difference in annualized percentage change in ganglion cell-inner plexiform layer thickness between drug-resistant and non-drug-resistant epilepsy groups

    Time frame: Baseline to 18 months after enrollment.

    Annualized percentage change in ganglion cell-inner plexiform layer thickness measured by macular optical coherence tomography will be compared between participants with drug-resistant epilepsy and participants without drug-resistant epilepsy. This analysis will be performed only among participants with epilepsy.

    Drug-resistant epilepsy will be defined as failure of adequate trials of two tolerated, appropriately chosen and used antiseizure medication schedules to achieve sustained seizure freedom.

    Unit of measure: Percent change per year

Secondary outcomes

  1. Change in hyperreflective foci count measured on optical coherence tomography

    Time frame: Baseline to 18 months after enrollment.

    Hyperreflective retinal foci (HRF) will be assessed with Heidelberg OCT at baseline and 18 months using fovea-centered 6 × 6 mm macular scans. Identical parameters will be applied at both visits. HRF will be counted twice per scan volume, and the mean of the two counts will be analyzed. For participants with two eligible eyes, the mean of both eyes will be used; if only one eye is eligible, that measurement will be included. Change will be calculated as the 18-month count minus the baseline count. Unit of measure: Number of hyperreflective foci

  2. Difference in hyperreflective retinal foci count between drug-resistant and non-drug-resistant epilepsy groups

    Time frame: Baseline to 18 months after enrollment.

    Hyperreflective retinal foci count measured on optical coherence tomography will be compared between participants with drug-resistant epilepsy and participants without drug-resistant epilepsy. This analysis will be performed only among participants with epilepsy. Hyperreflective retinal foci will be counted twice on the same scan volume, and the average count will be used for analysis.

    Unit of measure: Number of hyperreflective retinal foci

  3. Change in superficial macular vessel density measured by optical coherence tomography angiography

    Time frame: Baseline to 18 months after enrollment.

    Superficial macular vessel density will be measured using optical coherence tomography angiography at baseline and at 18 months. The OCTA device-derived superficial capillary plexus vessel density value will be recorded. The mean value of both eyes will be used for analysis.

    Unit of measure: Percentage points

  4. Change in deep macular vessel density measured by optical coherence tomography angiography

    Time frame: Baseline to 18 months after enrollment.

    Deep macular vessel density will be measured using optical coherence tomography angiography at baseline and at 18 months. The OCTA device-derived deep capillary plexus vessel density value will be recorded. The mean value of both eyes will be used for analysis.

    Unit of measure: Percentage points

  5. Change in peripapillary capillary vessel density measured by optical coherence tomography angiography

    Time frame: Baseline to 18 months after enrollment.

    Peripapillary capillary vessel density will be measured using optical coherence tomography angiography at baseline and at 18 months. The OCTA device-derived peripapillary capillary density value will be recorded. The mean value of both eyes will be used for analysis.

    Unit of measure: Percentage points

  6. Change in foveal avascular zone area measured by optical coherence tomography angiography

    Time frame: Baseline to 18 months after enrollment.

    Foveal avascular zone area will be measured using optical coherence tomography angiography at baseline and at 18 months. The OCTA device-derived foveal avascular zone area will be recorded. The mean value of both eyes will be used for analysis.

    Unit of measure: Square millimeters

  7. Change from baseline in serum interleukin-1 beta concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy

    Time frame: Baseline to 18 months after enrollment.

    Serum interleukin-1 beta concentration will be measured only in participants with epilepsy from peripheral venous blood samples collected at baseline and at 18 months. Measurements will be performed using a commercial enzyme-linked immunosorbent assay kit according to the manufacturer's protocol. Change from baseline will be calculated as the 18-month value minus the baseline value.

    Unit of measure: Picograms per milliliter(pg/mL)

  8. Change from baseline in serum C-C motif chemokine ligand 2 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy

    Time frame: Baseline to 18 months after enrollment.

    Serum C-C motif chemokine ligand 2 concentration will be measured only in participants with epilepsy from peripheral venous blood samples collected at baseline and at 18 months. Measurements will be performed using a commercial enzyme-linked immunosorbent assay kit according to the manufacturer's protocol. Change from baseline will be calculated as the 18-month value minus the baseline value.

    Unit of Measure: Picograms per milliliter(pg/mL)

  9. Change from baseline in serum soluble CD14 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy

    Time frame: Baseline to 18 months after enrollment.

    Serum soluble CD14 concentration will be measured only in participants with epilepsy from peripheral venous blood samples collected at baseline and at 18 months. Measurements will be performed using a commercial enzyme-linked immunosorbent assay kit according to the manufacturer's protocol. Change from baseline will be calculated as the 18-month value minus the baseline value.

    Unit of measure: Nanograms per milliliter(ng/mL)

  10. Change from baseline in serum soluble CD163 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy

    Time frame: Baseline to 18 months after enrollment.

    Serum soluble CD163 concentration will be measured only in participants with epilepsy from peripheral venous blood samples collected at baseline and at 18 months. Measurements will be performed using a commercial enzyme-linked immunosorbent assay kit according to the manufacturer's protocol. Change from baseline will be calculated as the 18-month value minus the baseline value.

    Unit of measure: Nanograms per milliliter(ng/mL)

  11. Association of mean monthly seizure frequency and baseline National Hospital Seizure Severity Scale score with annualized percentage change in peripapillary retinal nerve fiber layer thickness

    Time frame: Baseline to 18 months after enrollment.

    Among participants with epilepsy, mean monthly seizure frequency during follow-up will be calculated from seizure diaries and clinical records. Baseline seizure severity will be assessed with the National Hospital Seizure Severity Scale (NHS3), based on all seizure types experienced in the past 6 months and their severity. Annualized percentage change in peripapillary RNFL thickness will be derived from baseline and 18-month OCT measurements. Independent associations of seizure frequency and NHS3 total score with RNFL change will be evaluated using multivariable linear regression.

    Unit of Measure: Regression coefficient

  12. Association of mean monthly seizure frequency and baseline National Hospital Seizure Severity Scale score with annualized percentage change in ganglion cell-inner plexiform layer thickness

    Time frame: Baseline to 18 months after enrollment.

    Among participants with epilepsy, mean monthly seizure frequency during follow-up will be calculated from seizure diaries and clinical records. Baseline seizure severity will be assessed with the National Hospital Seizure Severity Scale (NHS3), based on all seizure types experienced in the past 6 months and their severity. Annualized percentage change in ganglion cell-inner plexiform layer (GC-IPL) thickness will be derived from baseline and 18-month OCT measurements. Independent associations of seizure frequency and NHS3 total score with GC-IPL change will be evaluated using multivariable linear regression. Unit of Measure: Regression coefficient

  13. Correlation between number of antiseizure medications and ganglion cell-inner plexiform layer thickness measured by optical coherence tomography

    Time frame: Baseline to 18 months after enrollment.

    The number of antiseizure medications will be recorded from clinical records. Ganglion cell-inner plexiform layer thickness will be measured using macular optical coherence tomography. The correlation between the number of antiseizure medications and ganglion cell-inner plexiform layer thickness will be assessed using Pearson or Spearman correlation according to data distribution.

    Unit of Measure: Correlation coefficient

  14. Difference in peripapillary retinal nerve fiber layer thickness across epilepsy syndrome groups

    Time frame: Baseline to 18 months after enrollment.

    Peripapillary retinal nerve fiber layer thickness measured by optical coherence tomography will be compared across epilepsy syndrome groups classified according to the International League Against Epilepsy classification. The mean value of both eyes will be used for analysis.

    Unit of Measure: Micrometers(µm)

  15. Difference in ganglion cell-inner plexiform layer thickness across epilepsy syndrome groups

    Time frame: Baseline to 18 months after enrollment.

    Ganglion cell-inner plexiform layer thickness measured by macular optical coherence tomography will be compared across epilepsy syndrome groups classified according to the International League Against Epilepsy classification. The mean value of both eyes will be used for analysis.

    Unit of Measure: Micrometers(µm)

  16. Predictive performance of a predefined retinal-inflammatory biomarker model for drug-resistant epilepsy status

    Time frame: Baseline to 18 months after enrollment.

    A predefined multivariable prediction model will include retinal structural measures, optical coherence tomography angiography-derived vascular measures, hyperreflective retinal foci count, and serum inflammatory biomarker concentrations. The model's ability to predict drug-resistant epilepsy status will be evaluated using the area under the receiver operating characteristic curve.

    Unit of Measure: Area under the receiver operating characteristic curve

  17. Change from baseline in National Hospital Seizure Severity Scale score among participants with epilepsy

    Time frame: Baseline to 18 months after enrollment

    The National Hospital Seizure Severity Scale (NHS3) will be administered to participants with epilepsy at baseline and 18 months. All seizure types experienced in the past 6 months and their severity will be evaluated, applying the same predefined seizure-selection rule at both visits. Change from baseline will be calculated as the 18-month NHS3 total score minus the baseline score.

    Unit of Measure: Points.

  18. Change from baseline in Turkish version of Liverpool Adverse Events Profile total score among participants with epilepsy

    Time frame: Baseline to 18 months after enrollment

    The Turkish version of Liverpool Adverse Events Profile (LAEP-TR) will be administered to participants with epilepsy at baseline and 18 months to assess patient-reported adverse effects of antiseizure medications. Change from baseline will be calculated as the 18-month LAEP-TR total score minus the baseline score.

    Unit of Measure: Points.

Sponsors and collaborators

Lead sponsor

Kemal Tutkavul

Other

Collaborators

  • Haydarpasa Numune Training and Research Hospital Department of Neurology
  • Haydarpasa Numune Training and Research Hospital Department of Ophthalmology
  • Health Institutes of Türkiye
  • Istanbul University Aziz Sancar Institute of Experimental Medicine

Registry information

Official study title

Retina-Based Biomarkers in Epilepsy: Structural and Microvascular OCT Changes and Inflammatory Markers (sCD14, sCD163, CCL2, IL-1β) in Relation to Pathophysiology, Phenotype, Prognosis, and Drug-Resistant Epilepsy (DRE)

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Jul 21, 2026
Registry last updated
Jul 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.