Evidence-based approaches for Empty Nose Syndrome management: a systematic review highlighting current treatments and future directions.

Background: Empty nose syndrome (ENS) is an iatrogenic condition that develops following turbinate surgery. ENS presents with paradoxical nasal obstruction, sensation of suffocation, nasal dryness, accompanied by a substantial psychological burden, resulting in a high suicide rate and a severely diminished quality of life. Available treatments for ENS are often ineffective, underscoring the need for innovative interventions. This systematic review provides a comprehensive overview of the current therapeutic strategies for ENS and evaluates their reported efficacy. Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Embase, Scopus, Web of Science, ClinicalTrials.gov, and EudraCT in August 2025. Of 788 identified studies, 44 met the inclusion criteria: English language, full-text availability, human subjects, primary focus on ENS treatment, and classification as research articles or case reports. Study characteristics were organized into macro-themes - study type, population, therapeutic approach, follow-up, outcomes, adverse events, and vascularization strategies - and related micro-themes. Results: The majority of studies were case series (30), while fewer studies consisted of case reports (8), case-control (3), cohort (3), and randomized controlled trials (1). Sample sizes were limited, with a predominance of male participants. Implant-based interventions were the most common (70.5%), followed by injection-based and neurostimulation approaches, while pharmacological and/or cognitive therapies were explored in three multimodal designs. Most studies had short-to mid-term follow-up, with 61.4% lasting less than 1 year. Outcomes were mainly assessed via questionnaires (75%) and clinical evaluations (50%), whereas biological analyses were rarely performed (9.1%). Postoperative adverse events were analysed in 64% of studies and predominantly occurred within the first month. Conclusion: This review highlights that ENS treatment research is largely dominated by descriptive and observational studies, reflecting the current limited evidence. The heavy reliance on subjective, questionnaire-based outcomes further increases the risk of bias, emphasizing the need for a deeper understanding of ENS pathogenesis and the integration of objective biological measures as outcome metrics. Building on the most promising approaches, future studies should focus on conducting larger randomised controlled trials to develop standardised, evidence-based treatment protocols for patients with ENS, involving different strategies to control the pathology.