Serum eye drops are eye drops prepared from the serum component of blood. They were first reported in 1975 as a treatment for tear deficiency in patients with ocular surface disease (OSD).
Serum contains bioactive components such as growth factors, vitamins, and fibronectin that are common with natural tears. These components, which are absent in artificial tears, promote ocular surface repair. Serum and tears have similar albumin content and osmolarity, and because they contain no preservatives, long-term use is possible.
The TFOS DEWS III report positions serum eye drops at Step 3 of the stepped treatment algorithm (when artificial tears and cyclosporine eye drops are insufficient) 1). The European League Against Rheumatism (EULAR) also recommends the use of autologous serum eye drops for patients whose symptoms are not controlled with ocular lubricants and cyclosporine A (CsA) 1).
However, factors such as insufficient standardization of preparation methods, high cost, and lack of FDA approval limit their widespread use 1).
They are considered for severe dry eye and ocular surface diseases that do not achieve sufficient improvement with conservative treatment using artificial tears or immunosuppressive eye drops (e.g., cyclosporine). In the TFOS DEWS III stepped treatment algorithm, they are positioned at Step 3.
Serum eye drops are indicated for a wide range of ocular surface diseases that do not improve with conservative or topical treatments.
For patients who cannot provide autologous serum, allogeneic serum (ALS) eye drops prepared from healthy donors can be used. Clinical trials have shown equivalent efficacy and tolerability between autologous and allogeneic serum. This is a useful alternative for patients with difficult venous access, elderly patients, and those with systemic or hematologic diseases.
Serum contains many bioactive components common to natural tears. Natural tears are a complex mixture containing over 1,500 proteins, cytokines, growth factors, and neurotransmitters 1). Serum eye drops supplement these endogenous components, inhibit apoptosis, and promote corneal epithelial cell proliferation, migration, and differentiation.
The main components and their actions are shown below.
| Component Category | Main Components | Action |
|---|---|---|
| Growth Factors | EGF, NGF, TGF-α | Epithelial growth and nerve regeneration |
| Vitamins | Vitamin A, E | Promotion of differentiation and antioxidant |
| Structural Proteins | Fibronectin | Cell adhesion and migration |
| Plasma proteins | Albumin | Antioxidant and ocular surface protection |
Albumin neutralizes reactive oxygen and nitrogen radicals via the free thiol group on Cys34, protecting the ocular surface from oxidative damage. Growth factors EGF and TGF-β have been reported to maintain activity even after storage at -20°C for 3 months.
Umbilical cord serum (UCS) has higher concentrations of EGF, TGF-β, NGF, and substance P compared to autologous serum 1).
In Japan, 20% autologous serum eye drops are prepared in-hospital according to the following procedure.
Since in-hospital preparation is cumbersome and carries a risk of bacterial contamination, the indication should be determined after comparing with other treatment options.
Autologous serum (AS)
Raw material: The patient’s own blood.
Preparation: After centrifugation, the serum is diluted to 20–50%.
Advantages: Low risk of infection transmission because it is autologous.
Limitations: Blood collection is required. In patients with inflammatory diseases, there is concern about elevated cytokines.
Allogeneic Serum (ALS)
Raw material: Blood from healthy donors.
Preparation: Same centrifugation and dilution process as autologous serum.
Advantages: Can be used in patients who are difficult to draw blood from. Infection screening has been performed.
Indications: Difficult venous access, elderly patients, patients with systemic diseases.
Platelet-Rich Plasma (PRP)
Raw material: Patient blood centrifuged in the presence of an anticoagulant.
Preparation: Used without dilution. Plasma containing platelets.
Advantages: Short preparation time. High concentration of growth factors and plasma factors.
Features: Intact platelets promote healing of the ocular surface.
A Cochrane review identified 29 studies, but only 5 met the inclusion criteria. Autologous serum eye drops may provide short-term symptom relief compared to artificial tears, but further RCTs are needed1).
A more recent meta-analysis of 7 RCTs reported that autologous serum eye drops were superior to artificial tears in both patient symptoms and clinical findings1).
The American Academy of Ophthalmology (AAO) Preferred Practice Pattern evaluation reviewed 10 studies, 8 of which were high quality, and showed that serum eye drops improved symptoms and at least one objective clinical finding1).
A study comparing 20% autologous serum eye drops with cyclosporine A 0.05% eye drops reported a significant reduction in OSDI score in the serum group1).
In an RCT of 38 patients with primary Sjögren’s syndrome, autologous serum eye drops and panretinal photocoagulation eye drops were used for 12 weeks. Corneal and conjunctival staining scores and TBUT improved significantly in both groups at 4 and 12 weeks. No significant difference was found between the groups1).
In 40 cases of corneal epithelial defects persisting after amniotic membrane transplantation, serum eye drops were reported to promote epithelial healing and better visual recovery compared to artificial tears1).
In a prospective randomized crossover trial of patients with severe dry eye, there was no difference in OSDI score between autologous and allogeneic serum, showing comparable efficacy and tolerability1).
In a double-blind RCT involving 63 patients with severe dry eye, three groups (autologous serum, allogeneic serum, and umbilical cord serum) were compared. Schirmer values, TBUT, fluorescein staining, and lissamine green staining all improved significantly. No significant differences were observed among the three groups 1).
RCTs and meta-analyses have shown that both autologous and allogeneic serum are effective in improving dry eye symptoms and signs. A Cochrane review found short-term symptom relief, and a meta-analysis of 7 RCTs reported superiority over artificial tears. However, standardization of preparation methods is insufficient, and further large-scale RCTs are needed.
Compared to artificial tears containing preservatives, the side effects of serum eye drops are minimal. As long as they are prepared and stored according to protocol, safety concerns are low.
The most important complication of serum eye drops is infection. However, it has been reported that the risk of infection is low as long as proper frozen and refrigerated storage is maintained.
The most concerning complication is infection due to bacterial contamination, but the risk is low as long as proper frozen and refrigerated storage protocols are followed. Serum eye drops do not contain preservatives, so long-term use is possible, but after opening, they must be stored at 4°C and used promptly.
