Ocular effects of novel synthetic opioids: A systematic review and narrative synthesis of current evidence.

INTRODUCTION: The recent emergence of novel synthetic opioids (NSOs), including fentanyl analogs-eg, carfentanil, acetylfentanyl-and nonfentanyl drugs-eg, U-47700, nitazenes-on the drug market has caused high levels of morbidity and mortality. Even though their systemic toxicities have been well documented, their ocular effects have not been well explored. This review thus engages to systematically review the currently available clinical and experimental data on NSO-related ocular complications. METHODS: According to Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines, the literature search was performed on PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar, which included all studies published up to May 2025. Our inclusion criterion entailed peer-reviewed articles on ocular outcomes following exposure of people to NSOs or in experimental animal models. Data extraction included study peculiarities, the type of opioids, ocular signs, and methodological quality. A narrative synthesis was performed due to heterogeneity in designs and outcomes. RESULTS: After a thorough search of the literature, 759 records were retrieved, with five being included in the study: one observational case series, two narrative reviews, one animal study, and one literature review. The reported ocular symptoms included miosis, blurred vision, dry eye syndrome, and corneal dysfunction. Increased activity of the µ-opioid receptor was associated with pupillary constriction and ocular surface disease. In one study, topical naltrexone was highlighted as a promising tool that can reverse the effects of opioids on the cornea. CONCLUSION: Evidence suggests that NSOs, in particular, fentanyl analogs and U-47700, are related to a consortium of ocular manifestations. Such effects are especially significant in cases of overdose. Future studies should explore long-term visual outcomes and assessment of targeted interventions, including ocular µ-opioid receptor antagonists.