Autologous Serum Eye Drops: Uses and Evidence

Autologous serum eye drops come from the patient’s own blood, and clinicians apply them to the ocular surface, and they provide a tear substitute that contains many of the factors found in natural tears.

Clinicians also use them for severe dry eye, persistent epithelial defects, and neurotrophic keratopathy that have not responded to conventional treatment.

The technique is old and widely used, but the evidence from trials is limited, and practice varies.

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What Are Autologous Serum Eye Drops?

Serum contains epidermal growth factor, vitamin A, fibronectin, nerve growth factor, and other components that support epithelial health.

It also contains albumin and other proteins that give it a pH, osmolarity, and buffering capacity similar to natural tears.

Unlike artificial tears, which are inert, the drops carry biologically active factors.

In addition, Tsubota and colleagues introduced the concept for dry eye in Sjögren syndrome in the late 1990s.

Platelet-rich plasma and umbilical cord serum are related products that have been tried with similar aims.

How the Drops Are Prepared

• Staff draw blood from the patient under sterile conditions
• Staff let it clot, commonly for a couple of hours at room temperature, and then centrifuge it
• Then staff separate the serum and dilute it with saline or balanced salt solution, most often to 20 percent, with concentrations up to 50 percent used in some regimens
• Staff aliquot the diluted serum into sterile vials or syringes and store it frozen
• Patient keeps one vial at a time in the refrigerator, and discards it after a short period, often 24 hours

Preparation requires a compounding pharmacy or a blood bank with proper quality control, and the regulations differ between countries.

Indications of Autologous Serum Eye Drops

• Severe dry eye, particularly Sjögren syndrome, that does not respond to conventional therapy
• Persistent epithelial defects, and recurrent corneal erosions (see recurrent corneal erosion)
• Neurotrophic keratitis, as an adjunct to other measures (see neurotrophic keratitis)
• Ocular graft-versus-host disease (see ocular GVHD)
• Superior limbic keratoconjunctivitis and filamentary keratitis in selected patients
• After corneal surgery and in some patients with limbal stem cell deficiency

Clinicians usually apply the drops four to eight times a day, with the frequency adjusted to the response.

Evidence

A Cochrane review of autologous serum for dry eye found that the trials were small and of low quality, and the benefit over artificial tears was uncertain.

Some trials showed improvements in symptoms and staining, but others found no significant difference.

For persistent epithelial defects and neurotrophic keratitis, the evidence is largely from case series, but clinical experience supports use.

The lack of high-quality trials means that you should also individualize decisions, and patients should understand that doctors consider the treatment supportive.

Autologous Serum Eye Drops: Risks and Practical Issues

• Contamination: the drops contain no preservative, so bacterial contamination during preparation or use can cause infectious keratitis
• Inconsistency: the composition differs from batch to batch and between patients
• Cost and logistics: repeated blood draws and a supply chain that may not be reimbursed
• Contraindications: patients with blood-borne infection, low hemoglobin, or inflammatory states that change serum composition

Teach patients to wash their hands, avoid touching the tip of the vial, and use the drops within the stated storage period.

Practical Approach

Try conventional treatment first, including preservative-free lubricants, punctal occlusion, and anti-inflammatory therapy (see dry eye disease).

Consider serum for patients with severe disease or an epithelial defect that fails to heal, and review the response at four to eight weeks.

Stop the drops if there is no benefit, and keep close follow-up in eyes at risk of infection.

Alternatives and Related Products

Platelet-rich plasma drops contain higher concentrations of growth factors and doctors have used them for persistent epithelial defects and severe dry eye.

Umbilical cord serum has a higher concentration of some neurotrophic factors, and some centers use it for neurotrophic keratitis.

Allogeneic serum from a screened donor is an option when the patient cannot provide blood.

Amniotic membrane products and topical nerve growth factor are other tools for the neurotrophic cornea (see amniotic membrane transplantation).

What to Tell the Patient

Explain that the drops come from their own blood, that they are free of preservatives, and that they must be stored and handled carefully.

Also, be clear that the benefit is not certain, that a trial of a few weeks is reasonable, and that continued use depends on a clear improvement.

Ask about the practical burden, because repeated blood draws and frozen storage are not feasible for every patient.

For the latest studies, see the PubMed results for autologous serum eye drops.

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References

1. Tsubota K, Goto E, Fujita H, et al. Treatment of dry eye by autologous serum application in Sjögren’s syndrome. Br J Ophthalmol. 1999;83:390-395.
2. Pan Q, Angelina A, Marrone M, Stark WJ, Akpek EK. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2017;2:CD009327.
3. Mannis MJ, Holland EJ, eds. Cornea. 4th ed. Elsevier; 2017.
4. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 8: External Disease and Cornea. AAO; current edition.