Tears provide much more than just lubrication to the ocular surface. Natural tears contain enzymes and proteins (growth factors, vitamins, immunoglobulins, neuropeptides) that regulate the corneal cells and promote ocular health. Tears also contain lymphocytes, macrophages and enzymes which have antimicrobial and bacteriostatic effects. This unique blend of factors creates an environment in the eye that is favorable for cellular regeneration, facilitating ocular surface healing.[1] When tears are inadequate, due to quantity or quality, the deficiency can create extreme discomfort, grittiness and irritation, and can damage the corneal epithelium, resulting in impaired vision. This condition, known as dry eye syndrome (DES), is an increasingly common problem, particularly in older individuals.[2]
Conventional therapies aim to reduce symptoms by replacing lubrication (artificial tears), minimizing tear loss (punctal occlusion, surgery), or reducing inflammation (topical cyclosporine/corticosteroids);[3] however, these therapies are unable to replace the vital biological components of natural tears. Autologous serum eye drops (ASED), on the other hand, contain many of these missing components, and have been clinically shown to improve symptoms and epithelial defects in patients who were unresponsive to conventional therapy.[4]
Why Blood?
Blood serum has many of the same properties and components found in natural tears, including several vital growth factors (EGF, Vitamin A, TGF-β, firbronectin, substance P, insulin-like growth factor 1 [IGF-1], NGF and other cytokines). These factors direct the cells through regeneration, so when they are missing in the eye due to DES, normal cellular maturation is prohibited and ocular surface wounds become much more difficult to heal.[5] Dr. Darren G. Gregory, associate professor of ophthalmology at the University of Colorado School of Medicine, discussed the benefits of ASED in the Nov 2016 Review of Ophthalmology:
“We think that the various growth factors and nutrients that are contained in the serum provide a lot of things for the surface of the eye that may be missing when the eye is very dry, or if there is scarring or other abnormality on the surface of the eye. It can often alleviate dry-eye symptoms in patients who have not had good relief from other available treatments. It can also help non-healing corneal epithelial defects.”[6]
In the Research
Autologous serum drops were first used in clinical trials in the 1970s.[7] In the 1980s, clinicians began prescribing ASED for ocular surface disease, and the prevalence of use further increased in the 1990s[8]. Multiple clinical trials, as well as in vitro laboratory trials have shown ASED to be a safe and effective method of treatment for recalcitrant dry eye syndrome. In a Level 3 study, 77 patients were surveyed before and after treatment with ASED, with follow-up questionnaires at 2 and 12 months. They were evaluated subjectively for dryness, ocular pain, and grittiness. Of the participants, 60% reported symptom reduction after 10 days, with the improvement reaching 79% by 2 months. These findings were sustained at the 12-month follow-up.[9]
Other clinical and laboratory studies have shown that ASED can help resolve epithelial defects, reduce inflammation,[10] and promote corneal reepithelization and wound healing.[11] The treatment has also been shown to significantly improve rose bengal and fluorescein scores in patients with Sjögren’s syndrome, and to encourage muc-1 upregulation in cultured cells.[12] With 30 years of experience in the field, ASED have a proven track record of safety and efficacy.
In recent years, ASED have been included in the protocol recommendations for treatment of dry eye syndrome. The American Academy of Ophthalmology has developed a Preferred Practice Pattern® for Dry Eye Syndrome that rates conditions on a three-tier scale from mild-moderate-severe. The PPP recommends autologous serum for patients with severe disease whose symptoms do not improve with traditional therapies.[13] Likewise, the Tear Film and Ocular Surface Society’s Dry Eye Workshop (TFOS DEWS) developed a recommended treatment plan based on a severity scale from 1(least severe) through 4 (most severe), and have indicated autologous serum eye drops for stage 3 patients.[14]
How They are Made
The manufacturing process is resource-intensive and varies somewhat by location, but the general process is the same. A patient donates a few vials of blood to the laboratory, and a technician centrifuges the blood for about 10 minutes to remove clotting factors. The remaining product, the blood serum, is then mixed with artificial tears or sterile saline to the appropriate concentration.[15] There is not currently a unified standard concentration, but research has shown that a 20% solution most accurately mimics the biological makeup of natural tears based on the concentration of TGF-β growth factors.[16],[17] The process typically produces a three-month supply of drops, which should be handled with care to prevent bacterial contamination. Although contamination has been observed, complications from such are rare.[18],[19],[20] Patients will be counseled to store any unopened bottles in the freezer, and to refrigerate the bottle currently in use.
Since the serum tears are a blood product, special care must be taken by the technicians to ensure their safety and to protect against the risk of infectious disease. For this reason, many laboratories will first screen potential patients for diseases such as Hepatitis B and C and HIV. Only a select few facilities and compounding pharmacies are willing to take on the challenge, and so access to the serum tears are limited.[21] This also contributes to the cost of the serum, which can be prohibitive for some. However, patients should consider the indirect savings they could see resulting from reducing or eliminating their use of OTC or prescription artificial tears while using ASED.[22]
Autologous serum eye drops have found a place in the treatment of severe dry eye that is resistant to conventional therapy. Christopher J. Rapuano, M.D. chief of the cornea service at Wills Eye Hospital in Philadelphia, highly recommends ASED. “Dry eye is a huge category including patients with severe ocular surface disease, chemical burns, Stevens-Johnson syndrome and ocular cicatricial pemphigoid. It (autologous serum) often helps them feel better, see better, and it helps the health of the ocular surface.” [23] Autologous serum is not for everybody, but for the right patient this alternative therapy can significantly improve quality of life and restore ocular surface heath.
[1] Anitua, E., Muruzabal, F., Tayebba, A., Riestra, A., Perez, V.L., Merayo-Lloves, J., and Orive, G. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta Ophthalmol. 2015; 93: e605-e614
[2] Dry Eye. American Optometric Assn. Retrieved from https://www.aoa.org/patients-and-public/eye-and-vision-problems/glossary-of-eye-and-vision-conditions/dry-eye?sso=y
[3] Anitua, E., Muruzabal, F., Tayebba, A., Riestra, A., Perez, V.L., Merayo-Lloves, J., and Orive, G. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta Ophthalmol. 2015; 93: e605-e614
[4] See references 9-12
[5] Anitua, E., Muruzabal, F., Tayebba, A., Riestra, A., Perez, V.L., Merayo-Lloves, J., and Orive, G. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta Ophthalmol. 2015; 93: e605-e614
[6] Brennan, K. (2016, Nov.) Thicker than water: Autologous Serum, the benefits and limitations of this unique corneal therapy. Review of Opthalmol. Retrieved from https://www.reviewofophthalmology.com/article/thicker-than-water-autologous-serum
[7] Ralph, R.A., Doane, M.G., and Dohlman, C.H. Clinical experience with a mobile ocular perfusion pump. Arch Ophthalmol. 1975; 93: 1039-1043.
[8] Hasson, M. (2012, Oct.) Autologous serum eye drops reduce ocular surface disease symptoms. Primary Care Optometry News. Retrieved from https://www.healio.com/optometry/cornea-external-disease/news/print/primary-care-optometry-news/%7B3e8ebb26-ec2f-415c-bda7-4a37a3a2f7d8%7D/autologous-serum-eye-drops-reduce-ocular-surface-disease-symptoms
[9] Mondy, P. Brama, T., Fisher, J., Gemelli, C.N., Chee, K., Keegan, A. Et al. Sustained benefits of autologous serum eye drops on self-reported ocular symptoms and vision-related quality of life in Australian patients with dry eye and corneal epithelial defects. Transfus Apher Sci. 2015; 53: 404-411.
[10] Semeraro. F., Forbice, E., Braga, O., Bova, A., Di Salvatore, A., and Azzolini, C. Evaluation of the efficacy of 50% autologous serum eye drops in different ocular surface pathologies. Biomed Res Int. 2014; 2014: 826970.
[11] Freire, V., Andollo, N., Etxebarria, J., Hernaez-Moya, R., Duran, J.A., and Morales, M.C. Corneal wound healing promoted by 3 blood derivatives: an in vitro and in vivo comparative study. Cornea. 2014; 33: 614-620.
[12] Tsubota, K., Goto, E., Fujita, H., Ono, M., Inoue, H., Saito, I. Et al. Treatment of dry eye by autologous serum application in Sjogren’s syndrome. Br J Ophthalmol. 1999; 83: 390-395.
[13] Ed. Garratt, S. American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern® Guidelines. Dry Eye Syndrome. San Francisco, CA: American Academy of Ophthalmology; 2013. Available at: www.aao.org/ppp
[14] Management and therapy of dry eye disease: report of the management and therapy subcommittee of the international dry eye WorkShop. Ocul Surf. 2007; 2007: 163–178.
[15] Mangan, R., and Lehman, S. (2012, March 15) How (and Why) to Make Autologous Serum. Review of Optometry. Retrieved from https://www.reviewofoptometry.com/article/how-and-why-to-make-autologous-serum#Dry%20Eye
[16] Hasson, M. (2012, Oct.) Autologous serum eye drops reduce ocular surface disease symptoms. Primary Care Optometry News. Retrieved from https://www.healio.com/optometry/cornea-external-disease/news/print/primary-care-optometry-news/%7B3e8ebb26-ec2f-415c-bda7-4a37a3a2f7d8%7D/autologous-serum-eye-drops-reduce-ocular-surface-disease-symptoms
[17] Anitua, E., Muruzabal, F., Tayebba, A., Riestra, A., Perez, V.L., Merayo-Lloves, J., and Orive, G. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta Ophthalmol. 2015; 93: e605-e614.
[18] Jones, L., Downie, L.E., Korb, D., Benitez-del-Castillo, J.M., Dana, R., Deng, S.X., Dong, P.N., Geerling, G., Yudi Hida, R., Liu, Y., Yul Seo, K., Tauber, J., Wakamatsu, T.H., Xu, J., Wolffsohn, J.S., and Craig, J.P. TFOS DEWS II Management and therapy report. Ocul Surf. 2017 July. 15; 3: 575-628.
[19] Prabhasawat, P., Chotikavanich, S., Leelaporn, A. Sterility of non-preservative eye drops. J Med Assoc Thai. 2005 Nov; 88 Suppl 9: s6-10.
[20] Thanathanee, O., Phanphruk, W., Anutarapongpan, O., Romphruk, A., and Suwan-Apichon, O. Contamination risk of 100% autologous serum eye drops in management of ocular surface diseases. Cornea. 2013; 32: 1116-1119.
[21] Hasson, M. (2012, Oct.) Autologous serum eye drops reduce ocular surface disease symptoms. Primary Care Optometry News. Retrieved from https://www.healio.com/optometry/cornea-external-disease/news/print/primary-care-optometry-news/%7B3e8ebb26-ec2f-415c-bda7-4a37a3a2f7d8%7D/autologous-serum-eye-drops-reduce-ocular-surface-disease-symptoms
[22] Mangan, R., and Lehman, S. (2012, March 15) How (and Why) to Make Autologous Serum. Review of Optometry. Retrieved from https://www.reviewofoptometry.com/article/how-and-why-to-make-autologous-serum#Dry%20Eye
[23] Brennan, K. (2016, Nov.) Thicker than water: Autologous Serum, the benefits and limitations of this unique corneal therapy. Review of Opthalmol. Retrieved from https://www.reviewofophthalmology.com/article/thicker-than-water-autologous-serum
