Ocular hemodynamics in epileptic children treated with antiepileptic drugs

Abstract

Purpose

To evaluate the quantitative measurements obtained for vessel density (VD) of the optic nerve head, macula, peripapillary retinal nerve fibre layer (p-RNFL) and total retinal thicknesses (Trt) by optical coherence tomography angiography (OCT-A) and the choroidal vascular structure using an image binarization method in children with epilepsy using three different antiepileptic drugs (AEDs) and to compare these measurements with healthy participants.

Methods

This observational, cross-sectional study included 124 patients divided into 4 groups: Group-1: patients receiving carbamazepine(n = 30), group-2: patients receiving levetiracetam (n = 31), group-3: patients receiving valproic acid (n = 32), and group 4: healthy controls (n = 31).A fully automated microstructural analysis of the VD of the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and the choriocapillaris (CC) layers and radial peripapillary capillary, and Trt, p-RNFL thickness were analyzed by using OCT-A. Enhanced depth imaging (EDI)-OCT scans of the macula were obtained and the images were binarized using the ImageJ software.

Results

The mean age, gender distribution and the duration of epilepsy were similar in all groups. Evaluation of the p-RNFL thickness and perifoveal Trt between the groups showed a statistically significant difference in all quadrants.The p-RNFL thickness was lower in patients receiving carbamazepine and valproic acid. The lowest values of the luminal area and choroidal vascular index (CVI) were found in patients receiving valproic acid; comparison with matched healthy controls showed statistically significant differences.

Conclusion

Valproic acid and carbamazepine are associated with thinning of the p-RNFL in epilepsy patients, but the macular and radial peripapillary VD were not affected.However, a reduction of choroidal vascular blood flow was found in epilepsy patients taking valproic acid.

Keywords

Epilepsy optic coherence tomography angiography peripapillary retinal nerve fibre layer thickness vessel density

Get full access to this article

View all access options for this article.

References

Aaberg

Gunnes

Bakken

, et al. Incidence and prevalence of childhood epilepsy: a nationwide cohort study. Pediatrics 2017; 139: e20163908.

Verrotti

Manco

Matricardi

, et al. Antiepileptic drugs and visual function. Pediatr Neurol 2007; 36: 353–360.

Walia

Khan

, et al. Side effects of antiepileptics-a review. Pain Pract 2004; 4: 194–203.

Richa

Yazbek

. Ocular adverse effects of common psychotropic agents. CNS Drugs 2010; 24: 501–526.

Hosking

Hilton

EJR

Embleton

, et al. Epilepsy patients treated with vigabatrin exhibit reduced ocular blood flow. Br J Ophthalmol 2003; 87: 96–100.

Farrell

Wolff

Teskey

. Neurodegeneration and pathology in epilepsy: clinical and basic perspectives. Adv Neurobiol 2017; 15: 317–334.

Teskey

Farrell

. Brief seizures induce a severe ischemic/hypoxic episode. Epilepsia 2012; 53: 104–105.

Farrell

Gaxiola-Valdez

Wolff

, et al. Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent. Elife 2016; 5: e19352.

Theodore

. Antiepileptic drugs and cerebral glucose metabolism. Epilepsia 1988; 29: 48–55.

10.

Matsuda

Fukuchi

Onuma

, et al. Interictal cerebral and cerebellar blood flow in temporal lobe epilepsy as measured by a non-invasive technique using Tc-99m HMPAO. Clin Nuc Med 1996; 21: 867–872.

11.

Spanaki

Siegel

Kopylev

, et al. The effect of vigabatrin (y-vinyl GABA) on cerebral blood flow and metabolism. Neurology 1999; 53: 1518–1522.

12.

Hilton

Hosking

Betts

. Epilepsy patients treated with antiepileptic drug therapy exhibit compromised ocular perfusion characteristics. Epilepsia 2002; 43: 1346–1350.

13.

Harris

Arend

Kopecky

, et al. Physiological perturbation of ocular and cerebral blood flow as measured by scanning laser ophthalmoscopy and color Doppler imaging. Surv Ophthalmol 1994; 38: 81–86.

14.

Harris

Tippke

Sievers

, et al. Acetazolamide And CO2: acute effects on cerebral and retrobulbar hemodynamics. J Glaucoma 1996; 5: 39–45.

15.

Schmetterer

Findl

Strenn

, et al. Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans. Am J Physiol 1997; 273: 2005–2012.

16.

Kiss

Dallinger

Findl

, et al. Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide. Am Physiol J 1999; 276: 1661–1667.

17.

Spaide

Klancnik

Cooney

. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol 2015; 133: 45–50.

18.

Claridge

Smith

. Diurnal variation in pulsatile ocular blood flow in normal and glaucomatous eyes. Surv Ophthalmol 1994; 38: 198–205.

19.

Agrawal

Salman

Tan

, et al.

Choroidal vascularity index (CVI)–a novel optical coherence tomography parameter for monitoring patients with panuveitis?

PLoS One 2016; 11: e0146344.

20.

Ikuno

Maruko

Yasuno

, et al. Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci 2011; 52: 5536–5540.

21.

Wang

Yin

. The application of enhanced depth imaging spectral domain optical coherence tomography in macular diseases. J Ophthalmol 2020 Aug 24; 2020: 1–7.

22.

Corvi

Sadda

. Evaluation of the inner choroid using OCT angiography. Eye (Lond) 2021; 35: 110–120.

23.

Nesper

Soetikno

Fawzi

. Choriocapillaris nonperfusion is associated with poor visual acuity in eyes with reticular pseudodrusen. Am J Ophthalmol 2017; 174: 42–55.

24.

Spaide

. Choriocapillaris flow features follow a power law distribution: implications for characterization and mechanisms of disease progression. Am J Ophthalmol 2016; 170: 58–67.

25.

Dennis

. Valproic acid, Encyclopedia of toxicology. 2nd ed. Cambridge: Academic Press, 2005.

26.

Kelly

McCulloch

. The effects of the GABAergic agonist muscimol upon the relationship between local cerebral blood flow and glucose utilization. Brain Res 1983; 258: 338–342.

27.

Blessing

Oertel

Willoughby

. Glutamic acid decarboxylase immunoreactivity is present in perikarya of neurons in nucleus tractus solitarius of rat. Brain Res 1984; 322: 346–350.

28.

Malinda Fitzgerald

ECM

Mar

, et al. Disinhibition of neurons of the nucleus of solitary tract that project to the superior salivatory nucleus causes choroidal vasodilation: implications for mechanisms underlying choroidal baroregulation. Neurosci Lett 2016; 633: 106–111.

29.

Reiner

Fitzgerald

MEC

Del Mar

, et al. Neural control of choroidal blood flow. Prog Retin Eye Res 2018; 64: 96–130.

30.

Agassandian

Fazan

Margaryan

, et al. A novel central pathway links arterial baroreceptors and pontine parasympathetic neurons in cerebrovascular control. Cell Mol Neurobiol 2003; 23: 463–478.

31.

Bill

. Some aspects of the ocular circulation. Friedenwald lecture. Invest Ophthalmol Vis Sci 1985; 26: 410–424.

32.

London

Benhar

Schwartz

. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol 2013; 9: 44–53.

33.

Gomceli

Dogan

Genc

, et al. Optical coherence tomography parameters in patients with photosensitive juvenile myoclonic epilepsy. Seizure 2016; 35: 36–40.

34.

Bayraktar Bilen

Titiz

Bilen

, et al. Optical coherence tomography and neurodegeneration in epilepsy. Eur J Ophthalmol 2021; 31: 252–257.

35.

Tak

AZA

Şengül

Ekmekçi

, et al. Comparison of optic coherence tomography results in patients with diagnosed epilepsy: findings in favor of neurodegeneration. Epilepsy Behav 2019; 92: 140–144.

36.

Balestrini

Clayton

MSL

Bartmann

, et al. Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy. J Neurol Neurosurg Psychiatry 2016; 87: 396–401.

37.

Dereci

Koca

Akçam

, et al. An evaluation of peripapillary retinal nerve fiber layer thickness in children with epilepsy receiving treatment of valproic acid. Pediatr Neurol 2015; 53: 53–57.

38.

Lobefalo

Rapinese

Altobelli

, et al. Retinal nerve fiber layer and macular thickness in adolescents with epilepsy treated with valproate and carbamazepine. Epilepsia 2006; 47: 717–719.

39.

Nalcacioglu

Icoz

Gultutan

, et al. Ocular perfusion characteristics of children with newly diagnosed epilepsy. Photodiagnosis Photodyn Ther 2023; 42: 103582.