Management of Glaucoma Medication Induced Dry Eye Disease with Self-retained Cryopreserved Amniotic Membrane

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Zarmeena Vendal


Approximately half of glaucoma patients have dry eye disease (DED) due to anti-glaucoma medication use. Herein, we evaluated the effectiveness of self-retained cryopreserved amniotic membrane (AM) in managing glaucoma-induced DED.

A retrospective chart review was conducted on consecutive patients treated with self-retained cryopreserved AM (Prokera Slim, BioTissue, Miami, FL) for ocular surface disease induced by chronic use of glaucoma medication. Data collected included demographics, diagnosis, associated signs and symptoms, concomitant therapies, and benefit duration.

Eight eyes of eight female patients (aged 80.0 ± 3.9 years) developed DED from chronic use (8.4 ± 2.3 years) of glaucoma medication. DED was refractory despite use of conventional therapies, including topical cyclosporine (n=7), gels (n=5), artificial tears (n=5), and lifitegrast (n=2). However, after treatment with self-retained cryopreserved AM, SPK grade significantly improved from 3.25 ± 0.7 to 0.38 ± 0.5 (p=0.01). Furthermore, visual acuity (VA) improved in all patients by an average of 1.4 ± 0.5 lines (range: 1-2), with a significant improvement in LogMAR VA observed post-treatment (logMAR .28 to .16, p=0.01). This was accompanied by decreased pain (n=5), decreased foreign body sensation (n=5), and improved comfort (n=2) that lasted an average duration of 5.3 ± 1.0 months.

This retrospective study suggests that a single placement of self-retained cryopreserved AM can restore corneal surface health with a lasting benefit in patients with glaucoma-induced DED who are refractory to conventional therapy directly or indirectly by promoting blinking and tearing reflexes.


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1. Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29(6):618-621.
2. Actis AG, Rolle T. Ocular surface alterations and topical antiglaucomatous therapy: a review. Open Ophthalmol J. 2014;8:67-72.
3. Terai N, Müller-Holz M, Spoerl E, Pillunat LE. Short-term effect of topical anti-glaucoma medication on tear-film stability, tear secretion, and corneal sensitivity in healthy subjects. Clinical ophthalmology (Auckland, NZ). 2011;5:517-525.
4. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17(5):350-355.
5. Kaštelan S, Tomić M, Metež Soldo K, Salopek-Rabatić J. How ocular surface disease impacts the glaucoma treatment outcome. Biomed Res Int. 2013;2013:696328.
6. McDonald MB, Sheha H, Tighe S, et al. Treatment outcomes in the DRy Eye Amniotic Membrane (DREAM) study. Clin Ophthalmol. 2018;9(12):677-681.
7. John T, Tighe S, Sheha H, et al. Corneal Nerve Regeneration after Self-Retained Cryopreserved Amniotic Membrane in Dry Eye Disease. J Ophthalmol. 2017;2017:10.
8. Cheng AM, Zhao D, Chen R, et al. Accelerated Restoration of Ocular Surface Health in Dry Eye Disease by Self-Retained Cryopreserved Amniotic Membrane. Ocular Surface. 2016;14(1):56-63.
9. Cheng AMS, Tighe S, H S, Tseng SC. Adjunctive role of self-retained cryopreserved amniotic membrane in treating immune-related dry eye disease. Int Ophthalmol. 2018;38(5):2219-2222.
10. Sheppard J, Yeu E, Tseng S. Sutureless Cryopreserved Amniotic Membrane Transplantation Accelerates Ocular Surface Healing and Topographic Stabilization for Dry Eye Patients. 2015.
11. Aguayo Bonniard A, Yeung JY, Chan CC, Birt CM. Ocular surface toxicity from glaucoma topical medications and associated preservatives such as benzalkonium chloride (BAK). Expert Opin Drug Metabol Toxicol. 2016;12(11):1279-1289.
12. Wong ABC, Wang MTM, Liu K, Prime ZJ, Danesh-Meyer HV, Craig JP. Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye. Ocular Surface. 2018;16(3):289-293.
13. Wilson WS, Duncan AJ, Jay JL. Effect of benzalkonium chloride on the stability of the precorneal tear film in rabbit and man. Br J Ophthalmol. 1975;59(11):667-669.
14. Herreras JM, Pastor JC, Calonge M, Asensio VM. Ocular surface alteration after long-term treatment with an antiglaucomatous drug. Ophthalmology. 1992;99(7):1082-1088.
15. Shafer B, Fuerst NM, Massaro-Giordano M, et al. The use of self-retained, cryopreserved amniotic membrane for the treatment of Sjogren syndrome: a case series. Digital journal of ophthalmology : DJO. 2019;25(2):21-25.
16. Tseng SC, Espana EM, Kawakita T, et al. How does amniotic membrane work? Ocular Surface. 2004;2(3):177-187.
17. Abidi A, Shukla P, Ahmad A. Lifitegrast: A novel drug for treatment of dry eye disease. J Pharmacol Pharmacother. 2016;7(4):194-198.
18. He H, Li W, Tseng DY, et al. Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-alpha-inhibitor (HC*HA) purified from extracts of human amniotic membrane. J Biol Chem. 2009;284(30):20136-20146.
19. He H, Tan Y, Duffort S, Perez VL, Tseng SC. In vivo downregulation of innate and adaptive immune responses in corneal allograft rejection by HC-HA/PTX3 complex purified from amniotic membrane. Investigative ophthalmology & visual science. 2014;55(3):1647-1656.
20. He H, Li W, Chen SY, et al. Suppression of activation and induction of apoptosis in RAW264.7 cells by amniotic membrane extract. Invest Ophthalmol Vis Sci. 2008;49(10):4468-4475.
21. He H, Zhang S, Tighe S, Son J, Tseng SC. Immobilized heavy chain-hyaluronic acid polarizes lipopolysaccharide-activated macrophages toward M2 phenotype. J Biol Chem. 2013;288(36):25792-25803.
22. He H, Kuriyan AE, Su C-W, et al. Inhibition of Proliferation and Epithelial Mesenchymal Transition in Retinal Pigment Epithelial Cells by Heavy Chain-Hyaluronan/Pentraxin 3. Sci Rep. 2017;7(1):43736.
23. Tighe S, Moein H-R, Chua L, Cheng A, Hamrah P, Tseng SCG. Topical Cryopreserved Amniotic Membrane and Umbilical Cord Eye Drops Promote Re-Epithelialization in a Murine Corneal Abrasion ModelAMUC for Promoting Re-Epithelialization. Invest Ophthalmol Vis Sci. 2017;58(3):1586-1593.
24. Meller D, Pires RT, Tseng SC. Ex vivo preservation and expansion of human limbal epithelial stem cells on amniotic membrane cultures. Br J Ophthalmol. 2002;86(4):463-471.
25. Grueterich M, Tseng SCG. Human limbal progenitor cells expanded on intact amniotic membrane. Arch Ophthalmol. 2002;120:783-790.
26. Meller D, Dabul V, Tseng SC. Expansion of conjunctival epithelial progenitor cells on amniotic membrane. ExpEye Res. 2002;74(4):537-545.
27. Koizumi N, Fullwood NJ, Bairaktaris G, Inatomi T, Kinoshita S, Quantock AJ. Cultivation of corneal epithelial cells on intact and denuded human amniotic membrane. Invest Ophthalmol Vis Sci. 2000;41(9):2506-2513.
28. Okada Y, Sumioka T, Ichikawa K, et al. Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4. Lab Investig; a journal of technical methods and pathology. 2019;99(2):210-230.
29. Shi X, Wang L, Clark JD, Kingery WS. Keratinocytes express cytokines and nerve growth factor in response to neuropeptide activation of the ERK1/2 and JNK MAPK transcription pathways. Regulatory peptides. 2013;186:92-103.
30. Yang L, Di G, Qi X, et al. Substance P promotes diabetic corneal epithelial wound healing through molecular mechanisms mediated via the neurokinin-1 receptor. Diabetes. 2014;63(12):4262-4274.
31. Mikulec AA, Tanelian DL. CGRP increases the rate of corneal re-epithelialization in an in vitro whole mount preparation. J Ocular Pharmacol Therapeut: the official journal of the Association for Ocular Pharmacology and Therapeutics. 1996;12(4):417-423.