Possible Signals of Ocular Disorders Associated with Gabapentinoids: A Three-Arm Study

Background: Gabapentinoids (gabapentin and pregabalin) are medications used to treat epilepsy and diabetic neuropathy. Reports of gabapentinoid-associated adverse drug reactions (ADRs) are increasing. This study aimed to explore these potential signals, with a focus on ocular adverse effects. Methods: A mixed-methods design was adopted, utilising quantitative and qualitative approaches encompassing: (I) a social listening approach using Reddit; (II) a pharmacovigilance retrospective disproportionality analysis study using serious reports to the FDA Adverse Event Reporting System (FAERS) (2015–2025); and (III) a literature review (2014–2025). Results: Reddit data revealed several user-reported adverse ocular effects, including blurred vision, diplopia and photosensitivity, across 78 and 40 identified reactions for gabapentin and pregabalin, respectively. Pharmacovigilance findings identified positive signals for eye disorders with both gabapentinoids compared to active control diazepam, amitriptyline and carbamazepine). Incidental findings highlighted potential discrepancies between FAERS data and undesired effects listed within the manufacturer’s literature, with pregabalin exhibiting higher reporting odds than gabapentin for cataract (ROR: 4.55; 95% CI: 2.51–8.26) and blindness (ROR: 2.63; 95% CI: 1.85–3.73). The literature review reinforced eye disorder concerns, specifically retinal effects with gabapentinoids, noting the absence of robust, high-quality research. Nevertheless, it identified a plausible biological mechanism involving the CACNA2D1 receptor in retinal cells of animal models, with evidence of an effect following oral administration of pregabalin. Conclusions: This study suggests an increase in eye disorder reports associated with gabapentinoid use. Further clinical and epidemiological studies are warranted to validate these real-world signals.