Autologous and Allogenic Serum Tears

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Article initiated by:
Amani Davis, Elena.Franco, Ken.K.Nischal
All contributors:
Amani Davis, Elena.Franco, Ken.K.Nischal, Colleen Halfpenny, M.D., Neha Shaik, MD, Amani Davis, Megan Kasetty, MD
Assigned editor:
Megan Kasetty, MD
Review:
Assigned status Update Pending
 by Megan Kasetty, MD on August 2, 2025.


Introduction

In the U.S. dry eye disease (DED) affects 16.4 million people, roughly 6.8% of the entire population.[1] It is likely that 6 million more Americans (2.5%) also suffer from symptoms of DED without a formal diagnosis, bringing the overall burden of DED to nearly 10% of the U.S. population.[2] Globally, prevalence is even higher: 11% of the world’s population suffer from DED.[3] DED makes up a large proportion of ocular surface disease (OSD), which includes but is not limited to inadequate lubrication of the ocular surface.

DED is a chronic disease that requires multiple treatment modalities. As of yet, there is no gold standard for DED treatment.[4] Current treatment includes environmental and behavioral modification, as well as medical and surgical therapies. Medical therapy often takes the form of topical ointments and drops/artificial tears. Surgical procedures include punctal plugs, punctual cautery and amniotic membrane placement. There are several formulations of drops including preservative-free artificial tears and serum eye drops (SEDs), which include autologous serum tears (AS) and allogeneic serum tears (ALS). Autologous serum tears were first described in 1975,[5] and since then, their use has become widespread. Because serum contains many components shared by natural tears, it was theorized that serum eye drops would improve dry eye by supplementing endogenous components, restoring the ocular surface. These components include vitamins, structural proteins, enzymes and growth factors. Importantly, serum and tears have similar albumin content and osmolality. These and other properties make tears derived from serum an attractive option for patients with severe DED as well as other OSD types, especially those who have not improved with first-line therapy. Further, because they are preservative free, SEDs can be used for prolonged periods. Finally, they have a limited side-effect profile as they are composed of endogenous components.

Background

AS tears were first reported in 1975 for the treatment of tear deficiency in a cohort of patients with varying OSD. AS tears successfully improved OSD related to several etiologies: systemic disease with ocular involvement, ocular surface pathology and post-operative patients.[5] Since this study, AS have been used for a variety of ocular surfaces disease states including severe DED, Sjogren syndrome, ocular graft versus host disease, Steven Johnson syndrome/toxic epidermal necrolysis, chemical burns, herpes keratitis, persistent corneal epithelial defect, and more.[6]

DED is the most common ocular surface disorder for which serum tears have been successfully used as a treatment. Clinical signs and symptoms may include fluctuating vision, ocular irritation, foreign body sensation and redness. Patients with intact corneal sensation often experience pronounced symptoms, which can facilitate earlier diagnosis and intervention. In contrast, patients with reduced corneal sensitivity may have more advanced disease despite fewer symptoms. For patients with severe DED, autologous serum (AS) tears can aid in restoring the integrity of the ocular surface by providing growth factors, vitamins, and other biologically active components naturally found in serum. Despite sharing endogenous origins, serum and natural tears differ significantly in their protein composition and concentration of growth factors.

While AS drops are derived from a patient’s own blood, allogenic serum (ALS) drops are prepared from donor serum and can be used in patients who are poor candidates for serum donation themselves. It is important to note that, presently, no preparation of serum tears has FDA approval for treatment of DED/OSD. However, multiple studies have shown their efficacy for signs and symptoms of DED and OSD.[7]

Basic Concepts

Tear Film

The tear film is the most superficial layer of the eye, and the first component of the visual pathway. Tears are produced in lacrimal glands and drained via the lacrimal drainage system. They are composed of an aqueous, mucin and lipid component. The tear film is essential for both vision and ocular health: it lubricates the surface of the eye and allows a smooth refractive surface for good vision. Normal tears contain vital proteins and growth factors that promote ocular health. The total protein content of tears is 7.51%, which is roughly 10% lower than serum’s protein content.[8] Major tear proteins include lysozyme, lactoferrin and albumin. Lysozyme protects against ocular surface infection. Lactoferrin binds and sequesters iron in the tear film, protecting the cornea from oxidative stress.

Pathophysiology of DED/OSD

DED is an ocular surface disease of multifactorial etiology. DED has been recently re-defined as a disease in which "loss of homeostasis of the tear film is the central pathophysiological concept.”[9] There are two major types of tear film dysfunction: evaporative and aqueous deficiency. These etiologies are not mutually exclusive, and in many cases both disease etiologies are present. Aqueous deficiency alone accounts for 10% of disease burden, while mixed aqueous and hyper evaporative-deficient accounts for more than 80% of DED cases.[10]

Evaporative tear film dysfunction is involved in most cases of DED. The leading cause of evaporative eye disease is meibomian gland dysfunction. Other causes include blinking abnormalities, contact lens use and topical drops with preservatives.[11] Current treatments for meibomian gland dysfunction begin with less-invasive treatment techniques including warm compresses, escalating to therapies such as corticosteroids or cyclosporine A.[10] Aqueous tear film dysfunction typically relates to lacrimal gland function. Autoimmune disease may play a role here as well, as in Sjogren’s disease. In aqueous deficient DED, glands may be obstructed, deficient or suffering from drug side effects.[11] Some experts argue that lid hygiene is more helpful in hyperevaporative dry eye, and plugs (silicon or collagen) can relieve signs and symptoms of hyposecretory DED, though they are useful in multifactorial cases, especially if drop application is problematic (elderly or very young patients).

DED/OSD Risk Factors: Women and older adults are at higher risk of DED, as well as patients with systemic disease, neurological deficits (e.g., decreased corneal sensation) nutritional deficiency (e.g., vitamin A deficiency), contact lens wear, UV radiation, oxidative stress, systemic inflammation, history of ocular surgery, as well as some medications.

Role of inflammation in DED: Several publications suggest that DED is an inflammatory disease with a mechanism similar to autoimmune diseases. These studies suggest a repetitive cycle of insult and inflammation to the ocular surface. For example, an environmental antigen will trigger release of inflammatory cytokines and other proteins which will activate T-cells on the ocular surface and lacrimal gland.[10][12] [13] Additionally, oxidative stress has been shown to play a role in DED as well. Studies have shown that imbalances between reactive oxygen species and protective enzymes may be associated with oxidative damage and inflammation on the ocular surface.[14]

Mechanism of Serum Tears

Most artificial tears contain 3 components: a preservative, cellulose and polyethylene glycol. Cellulose provides viscosity, and polyethylene glycol promotes surface coverage. These formulations are available in drop and ointment forms to suit patient preference. While these formulations serve to support the health of the ocular surface, they lack the growth factors and proteins that are found in serum and the healthy tear film.

Serum tears are a blood-derived biomaterial and are therefore high in platelet-derived growth factors.[15] Specifically, serum contains EGF, NNGF, TGF-alpha, KGF, HGF, IGF-1 and VEGF.[11] Further, serum contains vitamins A and E and fibronectin .[16] Together they serve to inhibit apoptosis and improve cell growth and migration.[17] Experts believe that the combination of growth factors facilitates cell expansion and differentiation and differentiation in vivo.[15]

By providing actual components of healthy tear substrate, serum tears target the mechanism underlying the patient's OSD. The cornea is composed of keratocytes: cells whose growth is stimulated by growth factors which are contained in platelet alpha granules. Importantly, studies have shown that the components that promote healing—growth factors EGF and TGF-B—were preserved when stored in a freezer for three months at -20 degrees C. Another study showing that serum tears actually reverse ocular pathology, demonstrates that serum tears promote corneal nerve regeneration.[18]

Finally, serum has a high albumin content, a protein known to have antioxidant properties. Specifically, albumin’s free thiol group on Cyst34 allows it to easily interact and neutralize free oxygen and nitrogen radicals.[19] This may offer protection to the ocular surface regarding oxidative damage.

Patient Selection

Indications

Serum tears are typically used for patients with a wide variety of ocular surface diseases who have not shown improvement with artificial tears, and other conservative/topical treatments. Most patients are good candidates for use of serum tears, whether autologous or allogeneic.

For patients to be serum donors, they should have good venous access, adequate Hb level, and prior evaluation and donation of 500ml of whole blood. It is also important to consider appropriate storage. Serum tears should be stored at -18 degrees Celsius, and the vials in use should be stored at 4 degrees Celsius.[20]

Contraindications

AS tear drops are contraindicated in patients who cannot tolerate repeated blood draws, but these patients are candidates for allogeneic tears. Factors that complicate serum donation include poor venous access, low Hb level, fear of needles, advanced patient age and limited mobility. Many of these factors disproportionately affect the elderly, as does DED/OSD.[20]

While there has been apprehension about the use of autologous serum tears in patients with communicable blood/serum diseases, this practice may still be done safely.[21] Still, it is prudent that caution be taken in patients with such diseases to prevent any possibility of contamination and disease transmission.

Barriers to use of serum tears

The largest barrier to serum tears at this time is the financial cost. Currently, serum tears are not FDA approved, and not covered by most insurance policies, making them cost prohibitive for many patients.

Autologous and allogeneic drops have comparable efficacy and tolerability for use in patients with severe dry eye disease. This makes the patient's ability to donate their own serum less of the barrier than it has been previously.[20]

Formulations

There are two popular formulations of serum tear derivatives: autologous serum and platelet rich plasma. To obtain serum for tear manufacture, a patient’s blood will be drawn, and centrifuged to separate blood into plasma, RBCs and WBC components. The serum component of blood will be extracted and refrigerated. Autologous serum production allows blood clotting in this process, which does allow inflammatory cytokines from monocytes and leukocytes. The solution may be diluted with saline 20-50%, which will reduce cytokine load.[22] Platelet rich plasma does contain platelets, with high concentrations for growth and plasma factors. It is not diluted prior to use, and it is believed that intact/inactivated platelet introduction to the ocular surface will promote ocular surface healing.

Side Effects & Safety

Compared to preserved artificial tears, there are several benefits, and few side effects associated with serum tears. Provided that they are produced and stored according to protocol, the safety concerns associated with autologous serum tears are minimal.

Studies & Trials

Current literature supports the use of serum tears in dry eye disease and persistent corneal epithelial defects;[23][24][25][26] however large, well-powered RCTs remain limited, particularly to evaluate the efficacy of serum tears in other ocular surface disease states.[27]

Dry eye disease

The majority of evidence supporting the use of serum tears comes from studies involving patients with DED. Reported improvements include increased tear film break up time, reduced corneal staining, and symptomatic relief as measured by the ocular surface disease index (OSDI) score.[26][24] One study demonstrated that AS tear use led to enhanced tear production, improved tear film stability, as well as increased number and density of conjunctival goblet cells.[28] Additionally, serum tears have shown efficacy in managing postoperative dry eye, particularly following LASIK, by reducing TBUT and reducing rose bengal staining score.[29]

Neuropathic corneal pain

Autologous serum tears have been shown to improve neuropathic corneal pain and promote corneal nerve regeneration, as demonstrated by in vivo confocal microscopy.[30][31]

Systemic inflammatory disease

Autologous serum tears have been shown to improve OSDI scores in patients with ocular manifestations of systemic disease including Sjogren syndrome, graft versus host disease, rheumatoid arthritis, systemic lupus erythematous (SLE) and Steven Johnson syndrome (SJS).[6] However, it is important to consider that patients with active systemic inflammatory disease may have altered serum composition compared to those without active systemic inflammation. Elevated levels of proinflammatory cytokines in the serum could potentially affect the therapeutic efficacy of AS tears. This raises ongoing questions about whether patients with higher baseline inflammatory markers may exhibit a diminished clinical response to AS therapy.

Persistent epithelial defect

Current literature supports the use of AS tears in the treatment of persistent epithelial defects, particularly when conventional therapies have failed. Serum tears have been shown to promote re-epithelialization of chronic defects.[32][33]

Autologous vs Allogeneic tears

Autologous and allogeneic drops have comparable efficacy and tolerability for use in patients with severe dry eye disease. One study showed no difference in OSDI score between patients treated with autologous and allogeneic serum drops. This study also showed no difference in tear break up time between the two groups.[20] This suggests that inability to donate serum does not mean that a patient cannot benefit from serum tears.

Complications

The most feared complication from serum tears is infection. While this complication has been reported, the risk of infection is low provided patients freeze and refrigerate their serum tears according to protocol.

Summary

First introduced in 1975, serum tears have become an effective second-line treatment for dry eye disease (DED) and a variety of ocular surface disorders (OSD). While conventional artificial tears support ocular surface hydration, they lack the growth factors, vitamins, and proteins naturally found in serum and the healthy tear film. In contrast, serum tears contain these bioactive components, which likely contribute to their efficacy in treating OSD that is refractory to standard artificial tears and topical medications.

References

  1. ↑ Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. 2017 Oct;182:90-98. doi: 10.1016/j.ajo.2017.06.033. Epub 2017 Jul 10. PMID: 28705660.
  2. ↑ O'Neil EC, Henderson M, Massaro-Giordano M, Bunya VY. Advances in dry eye disease treatment. Curr Opin Ophthalmol. 2019;30(3):166-178. doi:10.1097/ICU.0000000000000569
  3. ↑ Papas EB. The global prevalence of dry eye disease: A Bayesian view. Ophthalmic Physiol Opt. 2021 Nov;41(6):1254-1266. doi: 10.1111/opo.12888. Epub 2021 Sep 21. PMID: 34545606.
  4. ↑ Dogru M., Tsubota K. Pharmacotherapy of dry eye. Expert Opinion on Pharmacotherapy. 2011;12(3):325–334. doi: 10.1517/14656566.2010.518612. [PubMed]
  5. ↑ 5.0 5.1 Ralph RA, Doane MG, Dohlman CH. Clinical experience with a mobile ocular perfusion pump. Arch Ophthalmol. 1975;93(10):1039–1043.
  6. ↑ 6.0 6.1 Ripa M, Jabbehdari S, Yazdanpanah G, Lukacs E, Karcher B, Iqbal O, Bouchard C. The Role of Multisystem Disease in Composition of Autologous Serum tears and ocular surface symptom improvement. Ocul Surf. 2020 Jul;18(3):499-504. doi: 10.1016/j.jtos.2020.02.011. Epub 2020 Feb 29
  7. ↑ Beylerian M, Lazaro M, Magalon J, Veran J, Darque A, Grimaud F, Stolowy N, Beylerian H, Sabatier F, Hoffart L. Collyres de sérum autologue : traitement à long-terme dans le syndrome sec oculaire [Autologous serum tears: Long-term treatment in dry eye syndrome]. J Fr Ophtalmol. 2018 Mar;41
  8. ↑ Higuchi A, Takahashi K, Hirashima M, Kawakita T, Tsubota K. Selenoprotein P controls oxidative stress in cornea. PLoS One. 2010;5:e9911. © 2010 Higuchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
  9. ↑ Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20. PMID: 28736335.
  10. ↑ 10.0 10.1 10.2 Messmer EM. The pathophysiology, diagnosis, and treatment of dry eye disease. Dtsch Arztebl Int. 2015 Jan 30;112(5):71-81; quiz 82. doi: 10.3238/arztebl.2015.0071. PMID: 25686388; PMCID: PMC4335585.
  11. ↑ 11.0 11.1 11.2 Chan TCY, Chow SSW, Wan KHN, Yuen HKL. Update on the association between dry eye disease and meibomian gland dysfunction. Hong Kong Med J. 2019 Feb;25(1):38-47. doi: 10.12809/hkmj187331. Epub 2019 Jan 31. PMID: 30713149.
  12. ↑ Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye as a mucosal autoimmune disease. Int Rev Immunol. 2013;32:19–41.
  13. ↑ Stevenson W, Chauhan SK, Dana R. Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012;130:90–100.
  14. ↑ Seen S, Tong L. Dry eye disease and oxidative stress. Acta Ophthalmol. 2018 Jun;96(4):e412-e420. doi: 10.1111/aos.13526. Epub 2017 Aug 21. PMID: 28834388.
  15. ↑ 15.0 15.1 Tseng CL, Seghatchian J, Burnouf T. Animal models to assess the therapeutic efficacy of human serum and serum-converted platelet lysates for dry eye syndrome: Seeing is believing. Transfus Apher Sci. 2015 Aug;53(1):95-8. doi: 10.1016/j.transci.2015.05.016. Epub 2015 Jun 9. PMID: 26096279.
  16. ↑ Marks DC, Fisher J, Mondy P, Segatchian J, Dennington PM. Serum eye drop preparation in Australia: Current manufacturing practice. Transfus Apher Sci. 2015 Aug;53(1):92-4. doi: 10.1016/j.transci.2015.05.015. Epub 2015 Jun 9. PMID: 26123029.
  17. ↑ Blair P., Flaumenhaft R. Platelet alpha-granules: basic biology and clinical correlates. Blood Reviews. 2009;23(4):177–189. doi: 10.1016/j.blre.2009.04.001. [PMC free article]
  18. ↑ Aggarwal S, Kheirkhah A, Cavalcanti BM, Cruzat A, Colon C, Brown E, Borsook D, Prüss H, Hamrah P. Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy. Ocul Surf. 2015 Jul;13(3):250-62. doi: 10.1016/j.jtos.2015.01.005. Epub 2015 Feb 20. PMID: 26045233; PMCID: PMC4499014.
  19. ↑ Belinskaia DA, Voronina PA, Shmurak VI, Jenkins RO, Goncharov NV. Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties. Int J Mol Sci. 2021 Sep 25;22(19):10318. doi: 10.3390/ijms221910318. PMID: 34638659; PMCID: PMC8508759.
  20. ↑ 20.0 20.1 20.2 20.3 van der Meer PF, Verbakel SK, Honohan Á, Lorinser J, Thurlings RM, Jacobs JFM, de Korte D, Eggink CA. Allogeneic and autologous serum eye drops: a pilot double-blind randomized crossover trial. Acta Ophthalmol. 2021 Dec;99(8):837-842. doi: 10.1111/aos.14788. Epub 2021 Feb 15. PMID: 33590715.
  21. ↑ Marchand, M., Harissi-Dagher, M., Germain, M., Thompson, P., & Robert, M. C. (2018). Serum drops for ocular surface disease: national survey of Canadian cornea specialists. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie, 53(3), 266–271. https://doi.org/10.1016/j.jcjo.2017.09.007
  22. ↑ Ribeiro, M. V. M. R. , Nogueira Ribeiro, E. A. , & Ribeiro, L. F. (2018). The Use of Platelet-Rich Plasma in Dry Eye Disease. In Y. Tutar, & L. Tutar (Eds.), Plasma Medicine - Concepts and Clinical Applications. IntechOpen. https://doi.org/10.5772/intechopen.76090
  23. ↑ Cui D, Li G, Akpek EK. Autologous serum eye drops for ocular surface disorders. Curr Opin Allergy Clin Immunol. 2021 Oct 1;21(5):493-499. doi: 10.1097/ACI.0000000000000770. PMID: 34261888.
  24. ↑ 24.0 24.1 Bachtalia K, Plakitsi A, Palioura S. Autologous Serum Tears in the Management of Ocular Surface Diseases: A Comprehensive Review of Published Evidence. Semin Ophthalmol. 2025 Jun 14:1-7. doi: 10.1080/08820538.2025.2519049. Epub ahead of print. PMID: 40515592.
  25. ↑ Shtein RM, Shen JF, Kuo AN, Hammersmith KM, Li JY, Weikert MP. Autologous Serum-Based Eye Drops for Treatment of Ocular Surface Disease: A Report by the American Academy of Ophthalmology. Ophthalmology. 2020 Jan;127(1):128-133. doi: 10.1016/j.ophtha.2019.08.018. Epub 2019 Sep 24. PMID: 31561880.
  26. ↑ 26.0 26.1 He CZ, Zeng ZJ, Liu JQ, Qiu Q, He Y. Autologous serum eye drops for patients with dry eye disease: a systematic review and meta-analysis of randomized controlled trials. Front Med (Lausanne). 2024 Sep 13;11:1430785. doi: 10.3389/fmed.2024.1430785. PMID: 39346942; PMCID: PMC11427303.
  27. ↑ Pan Q, Angelina A, Marrone M, Stark WJ, Akpek EK. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2017 Feb 28;2(2):CD009327. doi: 10.1002/14651858.CD009327.pub3. PMID: 28245347; PMCID: PMC5510593.
  28. ↑ Valencia Castillo SL, Martín ES, García Frade LJ, García-Miguel FJ. Autologous serum eye drops improve tear production, both lachrymal flow and stability tests and conjunctival impression cytology with transfer in dry eye disease. Blood Transfus. 2021 Jan;19(1):45-53. Doi:
  29. ↑ Noda-Tsuruya T, Asano-Kato N, Toda I, Tsubota K. Autologous serum eye drops for dry eye after LASIK. J Refract Surg. 2006 Jan-Feb;22(1):61-6. doi: 10.3928/1081-597X-20060101-13. PMID: 16447938.
  30. ↑ Anam A, Liu C, Tong L, Liu YC. Blood-Derived Eye Drops for the Treatment of Corneal Neuropathic Pain. J Ocul Pharmacol Ther. 2024 Jun;40(5):281-292. doi: 10.1089/jop.2023.0155. Epub 2024 Apr 22. PMID: 38648544; PMCID: PMC11296151.
  31. ↑ Aggarwal S, Colon C, Kheirkhah A, Hamrah P. Efficacy of autologous serum tears for treatment of neuropathic corneal pain. Ocul Surf. 2019 Jul;17(3):532-539. doi: 10.1016/j.jtos.2019.01.009. Epub 2019 Jan 24. PMID: 30685437; PMCID: PMC6956846.
  32. ↑ von Hofsten J, Egardt M, Zetterberg M. The use of autologous serum for the treatment of ocular surface disease at a Swedish tertiary referral center. Int Med Case Rep J. 2016 Mar 2;9:47-54. doi: 10.2147/IMCRJ.S97297. PMID: 27042143; PMCID: PMC4780666.
  33. ↑ Arain MA, Dar AJ, Adeeb L. Autologous serum eye drops for the treatment of persistent corneal epithelial defects. J Coll Physicians Surg Pak. 2013 Oct;23(10):737-9. doi: 10.2013/JCPSP.737739. PMID: 24112261.
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