Serum Tear Production for Dry Eyes

This instructional video outlines the production of autologous serum tears for patients with severe dry eye disease (DED) unresponsive to conventional treatments. Derived from the patient’s own blood, serum tears offer biological components absent in artificial substitutes, such as growth factors and immunoglobulins. The process involves blood collection, coagulation, centrifugation, dilution with balanced salt solution, and sterile storage. Though preparation requires specialized equipment and presents logistical challenges, autologous serum tears provide a personalized, biologically compatible option for refractory DED. The video guides clinicians through each production step, supporting informed adoption of this advanced therapeutic approach in clinical practice.

Dry eye disease (DED) is characterized by tear film instability and ocular surface inflammation that can significantly impact quality of life.^1,2 While conventional therapies such as artificial tears, punctal plugs, and anti-inflammatory medications are frequently employed, a subset of patients with severe DED symptoms fail to respond adequately to these interventions. For these treatment-resistant cases, autologous serum tears have been investigated as an alternative therapeutic approach.^3,4

Serum tears can be used in patients with refractory ocular surface disease where conventional therapy is insufficient. Appropriate candidates include those with severe aqueous-deficient dry eye unresponsive to maximal lubrication and anti-inflammatory therapy, as well as patients with slow or non-healing epithelium or recurrent breakdown following ocular surface surgery (e.g., limbal transplantation, keratoprosthesis, keratoplasty, Tenon’s patch graft, or amniotic membrane use). They are also considered in chronic non-healing corneal epithelial defects associated with conditions such as graft-versus-host disease, post–ocular surface burns, chronic cicatrizing conjunctivitis, exposure or neurotrophic keratopathy, and radiation keratopathy. Serum tears may also be used in select cases of neuropathic ocular pain, reflecting their broader potential in patients with persistent epithelial or symptomatic compromise despite standard care.⁵

The biological basis for employing serum in ocular surface treatment is derived from its compositional similarity to natural tears. Human tears comprise over 3,000 different components, including growth factors, vitamins, and immunoglobulins that cannot be replicated in commercially manufactured lubricants.⁶

This video demonstrates the production of autologous serum tears, which is initiated with the collection of blood from the patient. Typically, four vials of blood are drawn to ensure sufficient serum can be harvested for the preparation of an adequate supply of tears. After collection, the blood is allowed to coagulate at room temperature.

Following a 20-minute coagulation period, the blood samples are centrifuged at 350 rotations per minute (RPM) for an additional 20 minutes. The centrifugation process facilitates the separation of serum from cellular blood components.

Once centrifugation is complete, the separated serum is carefully extracted and transferred to sterile vials that contain balanced salt solution (BSS). This BSS is a sterile physiological solution comprising sodium chloride, potassium chloride, calcium chloride, sodium acetate, and sodium citrate dehydrate. To achieve the typically desired concentration of at least 30% serum, approximately 1 mL of serum is combined with 2 mL of BSS in each vial.

Autologous serum eye drops have been studied in concentrations ranging from 20% to 100%, with most clinical use between 20% and 50%; the earliest report used a 33% dilution, and one study found 100% serum more effective than 50% in patients with Sjögren’s syndrome, though not for other dry eye etiologies. While there is no universal consensus on the optimal dilution, we prefer concentrations of at least 30% to ensure sufficient biologic activity. Reported adverse effects are rare—mostly limited to microbial growth in stored bottles, with no clinical sequelae in dry eye studies, although one case of microbial keratitis was documented in a persistent epithelial defect study. Overall, the evidence supports safety and efficacy, but protocol heterogeneity prevents firm recommendations on an exact optimal concentration.⁷

The prepared serum tears are stored frozen to maintain efficacy and prevent bacterial contamination. When required for use, one vial is transferred to refrigeration for weekly use, while the remaining supply is kept frozen. This approach is designed to preserve the therapeutic properties of the serum for an extended period, typically providing a three-month supply for the patient.

Autologous serum tears are primarily considered for patients with severe DED that has not improved with conventional treatments. Evidence from randomized trials summarized in a Cochrane review suggests that serum tears may provide short-term (about two weeks) symptom relief superior to artificial tears, but data beyond four weeks and on objective clinical measures remain inconclusive, so long-term benefit is uncertain.³

In practice, patients are typically instructed to instill the drops four to six times daily, with dosage tailored to symptom severity and response. Each vial is generally used for one week, and strict freezing/refrigeration protocols are required to minimize the risk of contamination or degradation.

Autologous serum tears remain sterile and biochemically stable when stored at −20 °C for up to 6 months, supporting less frequent blood draws and more efficient logistics. In practice, this allows a single donation to be processed into a long-term supply if proper aseptic preparation and freezing protocols are followed.⁸ However, when dispensing to patients, we usually limit distribution to 12 weeks’ supply to mitigate handling risk, and ensure patient safety in usage and storage.

Although serum tear therapy offers potential advantages, it comes with several constraints: the necessity for blood collection, complex preparation requiring specialized equipment and skilled staff, greater expense compared to standard tear substitutes, difficult storage conditions, and inconsistent composition across different preparations and individuals. Further research is warranted to standardize preparation protocols, optimize concentration ratios, and develop improved preservation methods. 

There are some practical alternatives for clinicians who may not have access to specialized compounding equipment or trained staff. In such settings, allogeneic serum eye drops prepared by hospital-based blood banks can serve as a viable substitute, ensuring sterility and standardization. For clinicians without access to serum-based therapies, optimizing conventional treatments (artificial tears, punctal occlusion, scleral lenses, or topical anti-inflammatory medications) remains essential while arranging referral to tertiary centers that can prepare serum tears. This tiered approach allows patients to receive effective care even in resource-limited environments, while minimizing delays in initiating treatment for severe or refractory ocular surface disease.

This instructional video provides essential knowledge for eye care professionals treating resistant DED. By demonstrating the step-by-step production of autologous serum tears, it enables clinicians to implement this specialized therapy in appropriate cases.

Nothing to disclose.