Autologous Serum Eye Drops: A Systematic Review, Part I—Characteristics, Preparation, Storage, and Stability

This two-part review provides a comprehensive overview of autologous serum eye drops (ASEDs), addressing their preparation (Part I) and clinical application in ocular surface diseases, particularly dry eye disease (DED) and persistent epithelial defects (PEDs) (Part II). Part I systematically reviews the current evidence on the characteristics, preparation, storage, stability, and microbiological safety of ASEDs. ASEDs contain multiple bioactive components, also present in tears, including growth factors, vitamins, cytokines, neurotrophic factors, antimicrobial proteins, and extracellular matrix-associated molecules, which may promote ocular surface homeostasis, epithelial regeneration, and wound healing. Particular attention is given to differences between natural tears and serum, as well as to disease-related changes in serum that may influence the biological properties and therapeutic efficacy of ASEDs. Preparation protocols vary considerably among studies and clinical centers, including variation in blood collection volume, clotting time, centrifugation parameters, dilution, filtration, storage temperature, and container type. These factors may influence the final concentration and stability of biologically active components and may also affect microbiological safety. Database searches identified 653 records, of which 288 were screened and 200 reports were assessed for eligibility; 75 studies met the inclusion criteria. After inclusion of eligible studies from the personal literature database and removal of overlap between the two sources, 198 unique studies were included in the systematic review. Although ASEDs are widely used as biologically active tear substitutes, further standardization of preparation, storage, and handling protocols is needed to improve product consistency and safety and to facilitate comparison and reproducibility of clinical outcomes.