Issue 1.2 : Dry Eyes, Volume 1: Ocular Surface Diseases

Preparation – Dry Eyes – SERUM EYEDROPS (SED)

Serum Eyedrops is considered an ideal tear film substitute as its composition closely resembles that of the natural tears. It should be considered as an adjunctive therapy in patients where the quality and production of the tear-film has been severely compromised, resulting in debilitating symptoms and a sight-threatening ocular surface disease (OSD). Its biological properties not only makes it an ideal lubricant, the nutrients in it promote the corneal epithelial cell renewal, restores homeostasis and immunological defence of the ocular surface. Despite this similarity, SED has failed to become a standard part of the armamentarium of Dry Eyes therapy and is used as an unlicensed medicine. 

Though most constituents of serum eyedrops (SED) and the tear-film are in a similar concentration, the serum has more of epitheliotrophic factors that promote corneal healing like tissue growth factors, fibronectin, vitamin A, albumin, Nerve growth factors, transforming growth factor‐β (TGF‐β) and lysozyme. Immunoglobulin A, vitamin C and epithelial growth factor (EGF) are in a lesser amount in SED than in tears. 

Indications for Serum Eyedrops:

  1. Severe Dry eyes, with aqueous deficiency, due to Sjögrens syndrome ( systemic lupus erythematosis, rheumatoid arthritis) or non Sjogrens dry eyes,  Stevens-Johnson syndrome, ocular pemphigoid and Graft versus Host Disease. Since it is an unlicensed medicine, it need not be considered in mild to moderate dry eyes.
  2. Corneal epithelial defects, both persistent & recurrent.
  3. Limbal epithelial stem cell failure (due to any cause).
  4. Neurotrophic keratopathy: which maybe congenital, or secondary to herpes zoster, autonomic neuropathy due to diabetes, damage to trigeminal nerve following neurosurgery or tumour or post-LASIK.
  5. Supportive therapy for exposure keratopathy, ocular surface reconstruction, severe ocular surface injury by chemicals, radiation or thermal injury.

Method of preparation

Serum eyedrops (SED) are not available commercially but have to be prepared from blood drawn from the patient (Auto-SED) or from donated blood (Allo-SED). Since serum is an ideal culture medium for all kinds of micro-organisms, a standard rigorous system has to be followed while preparing SED in order to optimise the safety of the product. They can be prepared in various concentrations of 20%, 40%, 50% or 100%, depending upon the clinical condition of the patient. Undiluted (100%) serum should not be used as some of its constituents, in high concentrations, can have detrimental affects on the ocular surface; the TGF‐β has antiproliferative effects, and in high concentration, it may suppress corneal epithelial wound healing.

The steps for the preparation of Auto-SED:

  1. Firstly, 100 mls blood is drawn from the patient /recipient, by a technician in a pathology lab, in a container without the addition of an anticoagulant.
  2. It is allowed to clot on its own for 1-2 hours. This allows the white & red blood cells to settle down in the clot.
  3. The supernatant / serum is taken in a vial and centrifuged to remove the platelets and any residual blood cells.
  4. After centrifugation, the serum is taken in a sterile container provided with a dropper.
  5. To prepare the desired concentration, for example 20%, 1 mls of serum is poured in each of the 20-30 sterilised vials. Then it is diluted with 4 mls of 0.9% saline to achieve the desired concentration. No preservative or antibiotic is added. 40% SED are prepared by diluting 2 mls serum with 3 mls 0.9% Saline while 50% serum, 2 mls serum is diluted with 2 mls of saline.
  6. The prepared vials are shaken to mix the serum and saline and placed in a freezer at -20*C.

Dispensing of SED: Whenever a fresh batch of serum vials is prepared, one vial from the batch must be assessed for a possible bacterial or fungal contamination. The bottles must be dispensed only if the results of the culture test are negative. The lysozyme in serum has some bacteriostatic affect but preparation of SED should be under extreme sterilised conditions and safe handling during instillation of SED must be adopted. 

The vials with frozen SED are dispensed in an icebox and instructed to be stored in a freezer at a temperature of -200C. They must be kept away from light to avoid degradation of vitamin A. One vial should be taken from the freezer at a time and used for 1-3 days; in between instillations, it should be kept refrigerated at 40C to retard the growth of microorganisms.

Side Effects:

SED are usually well tolerated with minimal side effects. 

  1. A few patients may complain of photophobia or discomfort due to epitheliopathy and delayed corneal healing.
  2. Immunoglobulin deposits may occur on the cornea.
  3. Vasculitis resulting in scleral melting may occur in patients with rheumatoid arthritis.
  4. The risk of serological transmission of diseases, like hepatitis, syphilis or HIV can occur and all donors for the Allo-SED must be screened for the same.

Contra-indications for the preparation of Auto-SED:

Blood cannot be taken from a patient who is less than age 16 years, has severe anaemia (Hb <11mg/dl), uncontrolled diabetes, a generally poor health, refractory auto-immune diseases and on cytotoxic therapy for the risk of such agents causing corneal and conjunctival toxicity.

Allo Serum Eye Drops: Donated blood can be used to prepare SED after it has been screened for hepatitis B / C, syphilis and HIV. From one full blood donation of 500 mLs, up to 150 bottles of 50% SED can be prepared and stored in a freezer at -4* C for a period of 12 months from the date of blood donation. They can be dispensed to patients in whom SED cannot be prepared from their own blood due to reasons mentioned above, or the clinical condition requires urgent treatment with SED. 

Patients with immune-mediated ocular surface diseases (Ocular pemphigoid, graft-versus-host disease and acute toxic epidermal necrolysis, Stevens-Johnson Syndrome) or diabetes have circulating auto-antibodies, pro-inflammatory cytokines and growth factors in their serum which can worsen the OSD.

Similarly, patients on cytotoxic drugs or sepsis may contain potentially harmful constituents in their serum so Auto-SED can lead to severe ocular surface toxicity. Therefore, Allo-SED rather than Auto-SED should be preferred in such cases.


  • The severity of OSD that may require serum eyedrops needs to be assessed with subjective and objective parameters; licensed treatments should be carefully considered prior to recommending SED.
  •  Monitoring the therapeutic affect of SED has to be by subjective and objective measures, in order to decide the frequency and duration of therapy.
  • A safe clinical practice needs to be adopted to document the efficacy, safety and any adverse reactions attributed to the SED.

4 thoughts on “Preparation – Dry Eyes – SERUM EYEDROPS (SED)

  1. Sansar Sangha says:

    Long time back, in 1960-70s,parotid duct transplantation was advocated for the treatment of severe keratoconjunctvitis like Steven Johnson and Sjogren s.I just wanted to know if it carried good sense. I would think it was a good palliative procedure but difficult to perform. Help of a general surgeon is required for the operation..I have done once only.Does any body else has ever seen or done it?.Did it have any justification or only a glitch of some body s brain .

    1. Dr Sameera Irfan says:

      Thanks Prof Sangha for your comment.
      I think if Dry Eyes are managed by a comprehensive approach, as we have suggested , then the need for such an invasive procedure does not arise.
      Medical therapy has to continue longterm for at least 1-2 years in severe cases. There is no short-cut to treating dry eyes.

  2. M Zaman soomro says:

    Autologous serum eye drops are very useful for severe dry eye . Should these used for mild to moderate dry eye in order to avoid preservative toxicity to corneal epithelium ?

  3. Dr Sameera Irfan says:

    Mild to moderate Dry Eyes improve with other measures mentioned in the therapy.
    However, if despite all those measures the symptoms and signs don’t improve, then SED should be used.

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