Autologous serum has been used to treat ocular surface disease since at least as early as 1975; then it was applied to the corneas of various patients via a mobile constant perfusion pump.1 An eye drop formulation using autologous serum was first described in 1984 was used successfully to treat keratoconjunctivitis sicca.2 In 1999 its use appears again, in two different articles.3 The first described its use in treating epithelial defects and the second in treating dry eye in patients with Sjögren’s syndrome. Since that time, this treatment option has only increased in popularity and is now frequently prescribed for severe and recalcitrant ocular surface disease.
Serum is known to contain numerous components essential to a healthy ocular surface. These include: fibronectin, vitamin A, ascorbic acid, neurotrophins, transforming growth factor (TGF-β), platelet-derived growth factors, neurotransmitters, immunoglobulins, cytokines, and epidermal growth factor. These ingredients promote migration, proliferation, and differentiation of limbal stem cells on the epithelium and have been shown to improve the morphology of corneal nerves. Another benefit of ASEDs is that the osmolarity and pH of serum is similar to that of naturally occurring healthy tears. In addition, these drops are typically free of preservatives and other additives.4-6
What are ASEDs used for?
ASEDs have become more popular for treating severe and/or recalcitrant cases of a variety of corneal conditions. These include: recurrent corneal erosion, severe dry eye disease, neurotrophic keratitis, corneal neuropathic pain, persistent epithelial defects, superior limbal keratoconjunctivitis, ocular graft-vs-host disease, Stevens-Johnson syndrome, ocular cicatrical pemphigoid, Mooren’s ulcer, corneal burns, limbal stem cell deficiency, and post procedures such as keratoplasty.4-6
Prescribing ASEDs can be a bit more complicated than is typically the case for many medications. A blood draw must be ordered, a phlebotomy facility selected and visited by the patient, blood drawn, the plasma separated and collected, the collected plasma must be transported to a compounding pharmacy, diluted to the prescribed concentration, bottled, and finally dispensed to the patient. Certain local compounding pharmacies can accommodate diluting the collected plasma into eye drops. The company Vital Tears provides a simplified system for ordering, producing, billing, and shipping ASEDs. They can provide various concentrations: 10%, 15%, 20%, 30%, and 40%. They have multiple price options including a six month subscription for $660. (Unfortunately, ASEDs are not typically covered by insurance.) The drops do need to be stored properly; they can be refrigerated for one week or frozen for six months.7 Some patients without access to a refrigerator during the day have found that a high quality thermos will maintain the proper temperature for quite some time.
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What needs to be considered with ASEDs?
As with all prescriptions, one needs to keep in mind the desired concentration, dosing frequency, and treatment duration. Unfortunately, none of those have been well established in the literature. While one could theoretically choose any desired concentration, 20% seems to be the one most commonly prescribed. Historically, this concentration became popular because an early study indicated that serum contains five times as much TGF-β as natural tears and TGF-β has been shown to suppress cell proliferation. However, subsequent studies have found that ASEDs and natural tears actually have similar concentrations of TGF-β. Therefore some advocate the use of higher concentrations. One study demonstrated some success with concentrations as high as 100%.3,4 Dosing regimens also widely vary, from three times per day to hourly, with eight times per day being commonly prescribed.8,9 The therapy is typically continued until a significant improvement or resolution of the signs and symptoms occurs and then is slowly tapered over weeks to months.8,9
For patients that ASEDs do not seem to be an appropriate treatment for, alternatives to traditional ASEDs have been proposed and studied. Plasma rich in growth factors eye drops are derived from plasma that has been treated with calcium chloride to enrich it with growth factors. One study showed promising results in patients with for ocular chronic graft versus host disease.10 Platelet rich plasma is plasma that has been treated to increase the concentration of platelets in the serum.11 Both of these options have been shown to be safe and effective.
ASEDs seem to have very few contraindications, and what exactly those are seems to vary depending on the source. Some possible contraindications worth considering would be: active infections, anemias, blood cancers, poor cardiovascular health, poor venous access, and poor patient access to a phlebotomy facility. For those patients, there are alternatives in the pipeline. Homologous serum eye drops are derived from the blood of another individual.12 Umbilical cord serum eye drops are derived from umbilical cords.13
For those challenging cases where conventional therapies are insufficient, you may want to consider serum-based tears.
References
- Pan Q, Angelina A, Zambrano A, et al. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2013;8(8):Cd009327.
- Fox RI, Chan R, Michelson JB, Belmont JB, Michelson PE. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum. 1984;27(4):459-461.
- Lekhanont K, Jongkhajornpong P, Choubtum L, Chuckpaiwong V. Topical 100% serum eye drops for treating corneal epithelial defect after ocular surgery. Biomed Res Int. 2013;2013:521315.
- Liu L, Hartwig D, Harloff S, et al. Corneal Epitheliotrophic Capacity of Three Different Blood-Derived Preparations. Investigative Ophthalmology & Visual Science. 2006;47(6):2438-2444.
- Semeraro F, Forbice E, Braga O, Bova A, Di Salvatore A, Azzolini C. Evaluation of the efficacy of 50% autologous serum eye drops in different ocular surface pathologies. Biomed Res Int. 2014;2014:826970.
- Quinto GG, Campos M, Behrens A. Autologous serum for ocular surface diseases. Arq Bras Oftalmol. 2008;71(6 Suppl):47-54.
- Tears V. How It Works. vitaltears.org. Accessed2019.
- Geerling G, Maclennan S, Hartwig D. Autologous serum eye drops for ocular surface disorders. Br J Ophthalmol. 2004;88(11):1467-1474.
- Dieckmann G, Goyal S, Hamrah P. Neuropathic Corneal Pain: Approaches for Management. Ophthalmology. 2017;124(11s):S34-s47.
- Anitua E, Sanchez M, Merayo-Lloves J, De la Fuente M, Muruzabal F, Orive G. Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation. Invest Ophthalmol Vis Sci. 2011;52(9):6066-6073.
- Alio JL, Arnalich-Montiel F, Rodriguez AE. The role of “eye platelet rich plasma” (E-PRP) for wound healing in ophthalmology. Curr Pharm Biotechnol. 2012;13(7):1257-1265.
- Harritshoj LH, Nielsen C, Ullum H, Hansen MB, Julian HO. Ready-made allogeneic ABO-specific serum eye drops: production from regular male blood donors, clinical routine, safety and efficacy. Acta Ophthalmol. 2014;92(8):783-786.
- Yoon KC, Heo H, Jeong IY, Park YG. Therapeutic effect of umbilical cord serum eyedrops for persistent corneal epithelial defect. Korean J Ophthalmol. 2005;19(3):174-178.
