Eye Disorders Associated with newer Antiepileptic drugs: A real-world disproportionality analysis of FDA Adverse Reporting System events

Background Newer antiepileptic drugs (AEDs), such as Levetiracetam (LEV), Lacosamide(LCM), Topiramate(TPM), Gabapentin(GBP), Oxcarbazepine(OXA), Lamotrigine(LTG) and Zonisamide(ZNS), are prescribed frequently for epilepsy by physicians. Simultaneously, they are known to be associated with a series of eye disorders. But very few studies have systemically compared eye disorders of newer AEDs in a large sample of patients diagnosed with epilepsy. Objective The aim of this study is to evaluate the association between eye disorders and several newer antiepileptic drugs (AEDs), including LEV, LTG, TPM, GBP, OXA, LCM, ZNS, as well as to look for differences in the frequency of AEs across individual AEDs, by data-mining a self-reporting database, the FDA Adverse Event Report System (FAERS). Methods The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis was used to detect the risk signals from the data in the US Food and Drug Administration (FDA) adverse event reporting system database (FAERS). The reporting odds ratio (ROR), the proportional reporting ratio (PRR) and χ2 (chi-square) were calculated to assess the association between adverse events (AEs) and AEDs use. Results FAERS reports of 158095 cases from January 1, 2015 to September 30, 2020 were included in this study. AEDs were associated with a series of eye related adverse events (AEs) defined by 106 Preferred Terms, which could be classified into ten aspects：Anterior eye structural change, deposit and degeneration, Glaucoma and ocular hypertension, Ocular haemorrhages and vascular disorders NEC (Not Elsewhere Classified), Ocular infections, irritations and inflammations, Ocular neuromuscular disorders, Ocular sensory symptoms NEC, Ocular structural change, deposit and degeneration NEC, Retina, choroid and vitreous haemorrhages and vascular disorders, Vision disorders, Eye disorders NEC. Conclusion Eye disorders occupy a certain proportion compared with other AEs associated with AEDs. There is variation in the types and severity of eye related AEs across individual AEDs. Generally, TPM and LTG are more likely to cause either mild or serious eye-related AEs. Patients with ophthalmic diseases should avoid using TPM and LTG. By contrast, LCM rarely has any severe eye related AEs, only diplopia and metamorphopsia are significant. LEV tend to produce ocular neuromuscular disorders related AEs. The adverse effects to macula induced by GBP should be taken into consideration during the clinic practice. ZNS appears to be heavily associated with choroidal effusion and angle closure glaucoma. OXA is mainly associated with lid lag and several cornea-related AEs.