Retinal OCT Changes and Biomarkers in Drug-Resistant Epilepsy

NCT07716930 | Enrolling By Invitation

• 2 other identifiers: 2024-KAEK-18/2026/1055435
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Epilepsy (Treatment Refractory); Epilepsy

Keywords

Drug Resistant Epilepsy; Biomarkers; Neurodegeneration; Neuroinflammation; Optical Coherence Tomography

Outcome Measures

Primary Outcomes (4)

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

  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

  Baseline to 18 months after enrollment.

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

  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

  Baseline to 18 months after enrollment

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

  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

  Baseline to 18 months after enrollment.

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

  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

  Baseline to 18 months after enrollment.

Secondary Outcomes (18)

• Change in hyperreflective foci count measured on optical coherence tomography

  Baseline to 18 months after enrollment.

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

  Baseline to 18 months after enrollment.

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

  Baseline to 18 months after enrollment.

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

  Baseline to 18 months after enrollment.

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

  Baseline to 18 months after enrollment.

Study Arms (3)

Epilepsy Group

Adults (n=150) aged 18 to 40 years with epilepsy for at least 1 year and currently receiving at least one antiseizure medication. Participants in this cohort will complete NHS3 and LAEP-TR assessments at baseline and at 18 months.

Control Group 1

Adults (n=50) aged 18 to 40 years with migraine, medication-overuse headache, or neuralgia who are currently receiving at least one antiseizure medication for a non-epileptic indication and have no history of epilepsy or unprovoked seizures.

Control Group 2(HC)

Healthy volunteers (n=50) aged 18 to 40 years with no known neurological or ophthalmological disease.

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The population will consist of three groups: patients with epilepsy (n=150), disease-control patients with chronic pain disorders using relevant medications (n=50) and healthy controls (n=50). Patients with epilepsy will include individuals diagnosed with epilepsy for at least 1 year and treated with at least one antiseizure medication. The epilepsy group will be further categorized according to drug-resistant epilepsy status. Participants with epilepsy will undergo NHS3 and LAEP-TR assessments at baseline and at 18 months using the same standardized administration procedures at both visits. The disease-control group (Control 1 group) will include patients with migraine, analgesic-overuse headache, or neuralgia who have been receiving relevant medication. Healthy controls (Control 2 group; HC) will include volunteers with no history of epilepsy, major neurological disease, ophthalmological disease, or regular antiseizure medication use.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Neurology Clinic

Istanbul, 34668, Turkey (Türkiye)

Location

Related Publications (21)

• Mermi-Dibek D, Kılıç B, Oztura İ, Baklan B. The liverpool adverse drug events profile (LAEP): Validity and reliability of Turkish version (LAEP-TR). Neurol Sci Neurophysiol 2023;40:101-5. DOI: 10.4103/nsn.nsn_83_23

  RESULT

• O'Donoghue MF, Duncan JS, Sander JW. The National Hospital Seizure Severity Scale: a further development of the Chalfont Seizure Severity Scale. Epilepsia. 1996 Jun;37(6):563-71. doi: 10.1111/j.1528-1157.1996.tb00610.x.

  PMID: 8641234 RESULT

• Aguilar-Castillo MJ, Estivill-Torrus G, Garcia-Martin G, Cabezudo-Garcia P, Lopez-Moreno Y, Ortega-Pinazo J, Ramirez-Garcia T, Ciano-Petersen NL, Serrano-Castro PJ. Inflammatory Drug-Resistant Epilepsy Index (IDREI) as a Molecular Compound Biomarker in Focal Epilepsies. Biomolecules. 2025 Jun 22;15(7):914. doi: 10.3390/biom15070914.

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• Rider F, Guekht A, Shpak A. Optical coherence tomography angiography in patients with focal epilepsy. Front Neurol. 2025 Jan 29;16:1529409. doi: 10.3389/fneur.2025.1529409. eCollection 2025.

  PMID: 39944552 RESULT

• Ahl M, Avdic U, Skoug C, Ali I, Chugh D, Johansson UE, Ekdahl CT. Immune response in the eye following epileptic seizures. J Neuroinflammation. 2016 Jun 27;13(1):155. doi: 10.1186/s12974-016-0618-3.

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• Pilotto E, Torresin T, Bacelle ML, De Moja G, Ferrara AM, Zovato S, Midena G, Midena E. Hyper-reflective retinal foci as possible in vivo imaging biomarker of microglia activation in von Hippel-Lindau disease. PLoS One. 2022 Aug 12;17(8):e0272318. doi: 10.1371/journal.pone.0272318. eCollection 2022.

  PMID: 35960779 RESULT

• Midena E, Torresin T, Velotta E, Pilotto E, Parrozzani R, Frizziero L. OCT Hyperreflective Retinal Foci in Diabetic Retinopathy: A Semi-Automatic Detection Comparative Study. Front Immunol. 2021 Apr 22;12:613051. doi: 10.3389/fimmu.2021.613051. eCollection 2021.

  PMID: 33968016 RESULT

• Cherkezzade M, Soylu S, Tuzun E, Yilmaz V, Sezgin M, Yapici Z, Kucukali CI, Topaloglu P. The Association Between Serum Levels of Glial Biomarkers, Clinical Severity and Electro-encephalography Features in Idiopathic West and Lennox-Gastaut Syndromes. Noro Psikiyatr Ars. 2024 Feb 2;61(2):128-134. doi: 10.29399/npa.28669. eCollection 2024.

  PMID: 38868840 RESULT

• Pranzatelli MR, Tate ED, McGee NR. Microglial/macrophage markers CHI3L1, sCD14, and sCD163 in CSF and serum of pediatric inflammatory and non-inflammatory neurological disorders: A case-control study and reference ranges. J Neurol Sci. 2017 Oct 15;381:285-290. doi: 10.1016/j.jns.2017.09.006. Epub 2017 Sep 6.

  PMID: 28991699 RESULT

• Stilund M, Reuschlein AK, Christensen T, Moller HJ, Rasmussen PV, Petersen T. Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis. PLoS One. 2014 Jun 2;9(6):e98588. doi: 10.1371/journal.pone.0098588. eCollection 2014.

  PMID: 24886843 RESULT

• Tan TH, Sequeira RP, Perucca P, Kwan P, O'Brien TJ, Monif M. Peripheral cytokine and monocyte phenotype associations in drug-resistant epilepsy. Sci Rep. 2025 Aug 13;15(1):29654. doi: 10.1038/s41598-025-14402-4.

  PMID: 40804444 RESULT

• Milano C, Montali M, Barachini S, Burzi IS, Pratesi F, Petrozzi L, Chico L, Morganti R, Gambino G, Rossi L, Ceravolo R, Siciliano G, Migliorini P, Petrini I, Pizzanelli C. Increased production of inflammatory cytokines by circulating monocytes in mesial temporal lobe epilepsy: A possible role in drug resistance. J Neuroimmunol. 2024 Jan 15;386:578272. doi: 10.1016/j.jneuroim.2023.578272. Epub 2023 Dec 23.

  PMID: 38160122 RESULT

• Ceska K, Papez J, Oslejskova H, Slaby O, Radova L, Loja T, Liba Z, Sverakova A, Brazdil M, Aulicka S. CCL2/MCP-1, interleukin-8, and fractalkine/CXC3CL1: Potential biomarkers of epileptogenesis and pharmacoresistance in childhood epilepsy. Eur J Paediatr Neurol. 2023 Sep;46:48-54. doi: 10.1016/j.ejpn.2023.06.001. Epub 2023 Jun 15.

  PMID: 37429062 RESULT

• Stauner L, Bao H, Delazer L, Kirsch I, Christmann T, Noachtar S, Havla J, Lauseker M, Kaufmann E. Longitudinal evaluation of retinal neuroaxonal loss in epilepsy using optical coherence tomography. Epilepsia. 2024 Dec;65(12):3644-3654. doi: 10.1111/epi.18139. Epub 2024 Oct 9.

  PMID: 39380535 RESULT

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• Chen Y, Xiong W, Lu L, Wu X, Cao L, Chen J, Xiao Y, Sander JW, Wu B, Zhou D. The thickness of the retinal nerve fiber layer, macula, and ganglion cell-inner plexiform layer in people with drug-resistant epilepsy. Epilepsia Open. 2024 Oct;9(5):1783-1792. doi: 10.1002/epi4.13004. Epub 2024 Aug 14.

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• Balestrini S, Clayton LM, Bartmann AP, Chinthapalli K, Novy J, Coppola A, Wandschneider B, Stern WM, Acheson J, Bell GS, Sander JW, Sisodiya SM. Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy. J Neurol Neurosurg Psychiatry. 2016 Apr;87(4):396-401. doi: 10.1136/jnnp-2015-310521. Epub 2015 Apr 17.

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum

MeSH Terms

Conditions

Epilepsy; Drug Resistant Epilepsy; Nerve Degeneration; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Inflammation

Study Officials

• KEMAL TUTKAVUL, Professor

  Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Neurology Clinic

  STUDY DIRECTOR

• NUR D BASPINAR, MD

  Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Neurology Clinic

  PRINCIPAL INVESTIGATOR

• ECE TURAN VARDAR, Professor

  Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Ophthalmology Clinic

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 21, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: "Beginning 12 months and ending 3 years after the publication of results"
• Access Criteria: A proposal that describes planned analyses must be submitted. A data sharing agreement must be signed. Contact the sponsor by e-mail.

Locations

TU (1)