Effects of topical autologous serum on the ocular surface in patients with toxic corneal epitheliopathy induced by anti-glaucoma drugs

  • Chang Ho Yoon
  • Hyun Ju Lee
  • Hye Youn Park
  • Hyungsuk Kim
  • Mee Kum Kim
  • Jin Wook Jeoung
  • Joo Youn OhEmail author
Original Paper



To investigate the effects of topical autologous serum application on the ocular surface in patients with toxic corneal epitheliopathy induced by anti-glaucoma drugs.


The patients who had corneal epitheliopathy because of preservative-containing anti-glaucoma eye drops were prospectively enrolled. The epitheliopathy was refractory to preservative-free artificial tear treatment. The patients topically applied 20% autologous serum to the eye eight times per day for 1 month. Baseline and one-month change in symptoms and signs were assessed by the Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time (TFBUT), Schirmer I values, corneoconjunctival staining scores, corneal sensitivity, InflammaDry® tear immunoassay, and tear cytokine profiles using a bead-based multiplex assay.


A total of ten consecutive patients were enrolled between January and August 2018 and evaluated after one-month treatment with 20% autologous serum eye drops. Significant improvement was observed in symptoms (OSDI scores from 25.5 ± 20.9 to 10.5 ± 12.0; P = .039), TFBUT (from 3.1 ± 1.8 s to 5.4 ± 2.3 s; P = .025), corneoconjunctival staining scores (from 7.7 ± 1.8 to 1.8 ± 1.9 NEI scale; P = .005), corneal sensitivity (from 4.6 ± .9 cm to 5.8 ± .5 cm; P = .013), and metalloproteinase-9 levels (P = .013). There were no significant changes in Schirmer I values and tear cytokine levels on multiplex assays. Treatment-related side effects were not detected.


Topical instillation of 20% autologous serum is an effective treatment for toxic corneal epitheliopathy associated with anti-glaucoma eye drops.

Trial registration number



Anti-glaucoma drug Autologous serum Benzalkonium chloride Cornea Ocular surface Toxicity 



This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2018R1A2B2004108).

Compliance with ethical standards

Conflict of interest

All authors have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board of Seoul National University Hospital (No. 1705-086-855). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was retrospectively registered on Clinical Research Information Service (CRiS), Republic of Korea (Trial registration number: KCT0003827) on 19/04/2019. The first registration date was 11/04/2018.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Aguayo Bonniard A, Yeung JY, Chan CC, Birt CM (2016) Ocular surface toxicity from glaucoma topical medications and associated preservatives such as benzalkonium chloride (BAK). Expert Opin Drug Metab Toxicol 12:1279–1289. CrossRefPubMedGoogle Scholar
  2. 2.
    Perez-Bartolome F, Martinez-de-la-Casa JM, Arriola-Villalobos P, Fernandez-Perez C, Polo V, Garcia-Feijoo J (2017) Ocular surface disease in patients under topical treatment for glaucoma. Eur J Ophthalmol 27:694–704. CrossRefPubMedGoogle Scholar
  3. 3.
    Anwar Z, Wellik SR, Galor A (2013) Glaucoma therapy and ocular surface disease: current literature and recommendations. Curr Opin Ophthalmol 24:136–143. CrossRefPubMedGoogle Scholar
  4. 4.
    Geerling G, Maclennan S, Hartwig D (2004) Autologous serum eye drops for ocular surface disorders. Br J Ophthalmol 88:1467–1474. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rauz S, Koay SY, Foot B, Kaye SB, Figueiredo F, Burdon MA, Dancey E, Chandrasekar A, Lomas R (2018) The Royal College of Ophthalmologists guidelines on serum eye drops for the treatment of severe ocular surface disease: executive summary. Eye 32:44–48. CrossRefPubMedGoogle Scholar
  6. 6.
    Moon J, Ko JH, Yoon CH, Kim MK, Oh JY (2018) Effects of 20% human serum on corneal epithelial toxicity induced by benzalkonium chloride: in vitro and clinical studies. Cornea 37:617–623. CrossRefPubMedGoogle Scholar
  7. 7.
    Lemp MA (1995) Report of the National Eye Institute/Industry workshop on clinical trials in dry eyes. CLAO J 21:221–232PubMedGoogle Scholar
  8. 8.
    Park JY, Kim BG, Kim JS, Hwang JH (2018) Matrix metalloproteinase 9 point-of-care immunoassay result predicts response to topical cyclosporine treatment in dry eye disease. Transl Vis Sci Technol 7:31. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kaufman HE (2013) The practical detection of mmp-9 diagnoses ocular surface disease and may help prevent its complications. Cornea 32:211–216. CrossRefPubMedGoogle Scholar
  10. 10.
    Oh JY, Choi H, Lee RH, Roddy GW, Ylostalo JH, Wawrousek E, Prockop DJ (2012) Identification of the HSPB4/TLR2/NF-kappaB axis in macrophage as a therapeutic target for sterile inflammation of the cornea. EMBO Mol Med 4:435–448. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sarkar J, Chaudhary S, Namavari A, Ozturk O, Chang JH, Yco L, Sonawane S, Khanolkar V, Hallak J, Jain S (2012) Corneal neurotoxicity due to topical benzalkonium chloride. Invest Ophthalmol Vis Sci 53:1792–1802. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Chen W, Zhang Z, Hu J, Xie H, Pan J, Dong N, Liu Z (2013) Changes in rabbit corneal innervation induced by the topical application of benzalkonium chloride. Cornea 32:1599–1606. CrossRefPubMedGoogle Scholar
  13. 13.
    Semeraro F, Forbice E, Nascimbeni G, Taglietti M, Romano V, Guerra G, Costagliola C (2016) Effect of autologous serum eye drops in patients with sjogren syndrome-related dry eye: clinical and in vivo confocal microscopy evaluation of the ocular surface. In Vivo 30:931–938CrossRefGoogle Scholar
  14. 14.
    Bradley JC, Simoni J, Bradley RH, McCartney DL, Brown SM (2009) Time- and temperature-dependent stability of growth factor peptides in human autologous serum eye drops. Cornea 28:200–205. CrossRefPubMedGoogle Scholar
  15. 15.
    Hussain M, Shtein RM, Sugar A, Soong HK, Woodward MA, DeLoss K, Mian SI (2014) Long-term use of autologous serum 50% eye drops for the treatment of dry eye disease. Cornea 33:1245–1251. CrossRefPubMedGoogle Scholar
  16. 16.
    Ziakas NG, Boboridis KG, Terzidou C, Naoumidi TL, Mikropoulos D, Georgiadou EN, Georgiadis NS (2010) Long-term follow up of autologous serum treatment for recurrent corneal erosions. Clin Exp Ophthalmol 38:683–687. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of OphthalmologySeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research InstituteSeoul National University HospitalSeoulRepublic of Korea
  3. 3.Tissue BankSeoul National University HospitalSeoulRepublic of Korea
  4. 4.Department of Laboratory MedicineSeoul National University HospitalSeoulRepublic of Korea

Personalised recommendations