Optimizing Autologous Serum Tear Therapy for Dry Eye Disease: Strategies and Innovations.

Autologous serum (AS) tears are an effective therapeutic option for advanced DED, mimicking the biochemical composition of natural tears. However, the absence of universally accepted guidelines has resulted in variability in AS tear concentration, diluents, processing of collected blood, and storage conditions, raising questions regarding the optimal parameters for AS tear use. This perspective provides a framework to inform clinical implementation and to guide future research on AS tear therapy optimization. PubMed, Scopus, and the Cochrane Library were searched for English-language articles from January 2022 through September 2025 using the terms "autologous serum," "dry eye disease," "dry eye syndrome," "dry eye," and "DED." Evidence suggests that AS tears diluted to 20% are widely used for moderate DED, whereas higher concentrations may provide faster, more pronounced and more durable improvements, particularly in severe cases. Levofloxacin-containing eye drops, artificial tears without emphasis on a specific component, sodium hyaluronate (SH)-containing eye drops, cyclosporine A (CsA)-containing ultra-nano emulsions, and methylcellulose have been investigated as alternatives to conventional diluents. Standardization of clotting, centrifugation and storage parameters is expected to enhance efficacy of AS tears and ensure stability of growth factors. Combination with estrogen replacement therapy in perimenopausal women or with topical insulin eye drops, as well as perioperative prophylactic use in patients with graft-versus-host disease (GVHD)-associated dry eye undergoing cataract surgery, represent emerging applications of AS tears that demonstrate potential to improve therapeutic outcomes. Overall, this perspective highlights the need for consensus protocols, supports severity-based concentration tailoring, and notes that diluents and processing methods require further refinement.