Retinal OCT Changes and Biomarkers in Drug-Resistant Epilepsy

Официальное название

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)

Обзор

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).

Подробное описание

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.

Первичные конечные точки

• Annualized percentage change in peripapillary retinal nerve fiber layer thickness measured by OCT [Срок оценки: Baseline to 18 months after enrollment.]
• Annualized percentage change in ganglion cell-inner plexiform layer thickness measured by OCT [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline to 18 months after enrollment.]

Вторичные конечные точки (12)

• Change in hyperreflective foci count measured on optical coherence tomography [Срок оценки: Baseline to 18 months after enrollment.]
• Difference in hyperreflective retinal foci count between drug-resistant and non-drug-resistant epilepsy groups [Срок оценки: Baseline to 18 months after enrollment.]
• Change in superficial macular vessel density measured by optical coherence tomography angiography [Срок оценки: Baseline to 18 months after enrollment.]
• Change in deep macular vessel density measured by optical coherence tomography angiography [Срок оценки: Baseline to 18 months after enrollment.]
• Change in peripapillary capillary vessel density measured by optical coherence tomography angiography [Срок оценки: Baseline to 18 months after enrollment.]
• Change in foveal avascular zone area measured by optical coherence tomography angiography [Срок оценки: Baseline to 18 months after enrollment.]
• Change from baseline in serum interleukin-1 beta concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy [Срок оценки: Baseline to 18 months after enrollment.]
• Change from baseline in serum C-C motif chemokine ligand 2 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy [Срок оценки: Baseline to 18 months after enrollment.]
• Change from baseline in serum soluble CD14 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy [Срок оценки: Baseline to 18 months after enrollment.]
• Change from baseline in serum soluble CD163 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy [Срок оценки: Baseline to 18 months after enrollment.]
• 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 [Срок оценки: Baseline to 18 months after enrollment.]
• 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 [Срок оценки: Baseline to 18 months after enrollment.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Turkey (Türkiye) · 1 центр

• Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Neurology Cl — Istanbul

Публикации

• 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
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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
• 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
• 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

Идентификаторы

NCT: NCT07716930 · 2024-KAEK-18/2026/10 · 55435

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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