Lacripep for Corneal Wound Healing Study

Summary

The objective of this study is to evaluate the safety and effectiveness of Lacripep as a therapy for superficial corneal injury repair after Photorefractive keratectomy (PRK).

Timeline

Start

2025-05-23

Primary completion

2027-06

Completion

2027-09

Publications

• Background Yulek F, Ozdek S, Gurelik G, Hasanreisoglu B. Effect of topical steroids on corneal epithelial healing after vitreoretinal surgery. Acta Ophthalmol Scand. 2006 Jun;84(3):319-22. doi: 10.1111/j.1600-0420.2005.00632.x.
• Background Wong HL, Poon SHL, Bu Y, Lo ACY, Jhanji V, Chan YK, Shih KC. A Systematic Review on Cornea Epithelial-Stromal Homeostasis. Ophthalmic Res. 2021;64(2):178-191. doi: 10.1159/000509030. Epub 2020 May 29.
• Background Wolsey D, Slade S, Wirostko BM, Brandano LA, Mann BK, Durrie DS, Thompson V. Novel Cross-Linked Ocular Bandage Gel Improves Reepithelialization After Photorefractive Keratectomy: A Randomized, Masked Prospective Study. J Ocul Pharmacol Ther. 2020 Oct;36(8):602-608. doi: 10.1089/jop.2019.0156. Epub 2020 Jul 17.
• Background Wilson SE. Interleukin-1 and Transforming Growth Factor Beta: Commonly Opposing, but Sometimes Supporting, Master Regulators of the Corneal Wound Healing Response to Injury. Invest Ophthalmol Vis Sci. 2021 Apr 1;62(4):8. doi: 10.1167/iovs.62.4.8.
• Background Wilson SE. Corneal wound healing. Exp Eye Res. 2020 Aug;197:108089. doi: 10.1016/j.exer.2020.108089. Epub 2020 Jun 15.
• Background Weng TH, Chang YM, Lin FH, Weng ZX, Wang TW, Chen YH, Tai MC, Chen JT, Liang CM, Lin TY. Investigation of corneal epithelial thickness and irregularity by optical coherence tomography after transepithelial photorefractive keratectomy. Clin Exp Optom. 2024 Jan;107(1):23-31. doi: 10.1080/08164622.2023.2197107. Epub 2023 Apr 20.
• Background Weichel ED, Colyer MH, Ludlow SE, Bower KS, Eiseman AS. Combat ocular trauma visual outcomes during operations iraqi and enduring freedom. Ophthalmology. 2008 Dec;115(12):2235-45. doi: 10.1016/j.ophtha.2008.08.033.
• Background Wang W, Despanie J, Shi P, Edman-Woolcott MC, Lin YA, Cui H, Heur JM, Fini ME, Hamm-Alvarez SF, MacKay JA. Lacritin-mediated regeneration of the corneal epithelia by protein polymer nanoparticles. J Mater Chem B. 2014 Dec 14;2(46):8131-8141. doi: 10.1039/C4TB00979G.
• Background Wang N, Zimmerman K, Raab RW, McKown RL, Hutnik CM, Talla V, Tyler MF 4th, Lee JK, Laurie GW. Lacritin rescues stressed epithelia via rapid forkhead box O3 (FOXO3)-associated autophagy that restores metabolism. J Biol Chem. 2013 Jun 21;288(25):18146-61. doi: 10.1074/jbc.M112.436584. Epub 2013 May 2.
• Background Wang J, Wang N, Xie J, Walton SC, McKown RL, Raab RW, Ma P, Beck SL, Coffman GL, Hussaini IM, Laurie GW. Restricted epithelial proliferation by lacritin via PKCalpha-dependent NFAT and mTOR pathways. J Cell Biol. 2006 Aug 28;174(5):689-700. doi: 10.1083/jcb.200605140. Epub 2006 Aug 21.
• Background Vlasov A, Sia RK, Ryan DS, Mines MJ, Stutzman RD, Rivers BA, Tseng SC, Bower KS. Sutureless cryopreserved amniotic membrane graft and wound healing after photorefractive keratectomy. J Cataract Refract Surg. 2016 Mar;42(3):435-43. doi: 10.1016/j.jcrs.2015.11.045.
• Background Vlasov A, Ryan DS, Ludlow S, Coggin A, Weichel ED, Stutzman RD, Bower KS, Colyer MH. Corneal and Corneoscleral Injury in Combat Ocular Trauma from Operations Iraqi Freedom and Enduring Freedom. Mil Med. 2017 Mar;182(S1):114-119. doi: 10.7205/MILMED-D-16-00041.
• Background Vijmasi T, Chen FY, Balasubbu S, Gallup M, McKown RL, Laurie GW, McNamara NA. Topical administration of lacritin is a novel therapy for aqueous-deficient dry eye disease. Invest Ophthalmol Vis Sci. 2014 Jul 17;55(8):5401-9. doi: 10.1167/iovs.14-13924.
• Background Townley R. The state of refractive surgery in the U.S. Air Force. Presented at: Military Refractive Safety and Standards Symposium; January 7-10, 2019; San Diego, CA
• Background Tomas-Juan J, Murueta-Goyena Larranaga A, Hanneken L. Corneal Regeneration After Photorefractive Keratectomy: A Review. J Optom. 2015 Jul-Sep;8(3):149-69. doi: 10.1016/j.optom.2014.09.001. Epub 2014 Oct 23.
• Background Tauber J, Laurie GW, Parsons EC, Odrich MG; Lacripep Study Group; Lacripep Study Group. Lacripep for the Treatment of Primary Sjogren-Associated Ocular Surface Disease: Results of the First-In-Human Study. Cornea. 2023 Jul 1;42(7):847-857. doi: 10.1097/ICO.0000000000003091. Epub 2022 Jul 28.
• Background Sia RK, Ryan DS, Stutzman RD, Pasternak JF, Eaddy JB, Logan LA, Torres MF, Bower KS. Wavefront-guided versus wavefront-optimized photorefractive keratectomy: Clinical outcomes and patient satisfaction. J Cataract Refract Surg. 2015 Oct;41(10):2152-64. doi: 10.1016/j.jcrs.2015.10.054.
• Background Sridhar MS. Anatomy of cornea and ocular surface. Indian J Ophthalmol. 2018 Feb;66(2):190-194. doi: 10.4103/ijo.IJO_646_17.
• Background Sedaghat MR, Momeni-Moghaddam H, Gazanchian M, Reinstein DZ, Archer TJ, Randleman JB, Hosseini SR, Nouri-Hosseini G. Corneal Epithelial Thickness Mapping After Photorefractive Keratectomy for Myopia. J Refract Surg. 2019 Oct 1;35(10):632-641. doi: 10.3928/1081597X-20190826-03.
• Background Sanghi S, Kumar R, Lumsden A, Dickinson D, Klepeis V, Trinkaus-Randall V, Frierson HF Jr, Laurie GW. cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland. J Mol Biol. 2001 Jun 29;310(1):127-39. doi: 10.1006/jmbi.2001.4748.
• Background Samudre S, Lattanzio FA Jr, Lossen V, Hosseini A, Sheppard JD Jr, McKown RL, Laurie GW, Williams PB. Lacritin, a novel human tear glycoprotein, promotes sustained basal tearing and is well tolerated. Invest Ophthalmol Vis Sci. 2011 Aug 5;52(9):6265-70. doi: 10.1167/iovs.10-6220.
• Background Ryan DS, Sia RK, Stutzman RD, Pasternak JF, Howard RS, Howell CL, Maurer T, Torres MF, Bower KS. Wavefront-Guided Versus Wavefront-Optimized Photorefractive Keratectomy: Visual and Military Task Performance. Mil Med. 2017 Jan;182(1):e1636-e1644. doi: 10.7205/MILMED-D-15-00576.
• Background Reynolds ME, Gu W. A new approach to categorization of ocular injury among U.S. Armed Forces. MSMR. 2022 Feb 1;29(2):8-14.
• Background Pflugfelder SC. Advances in the diagnosis and management of keratoconjunctivitis sicca. Curr Opin Ophthalmol. 1998 Aug;9(4):50-3. doi: 10.1097/00055735-199808000-00009.
• Background Pastor JC, Calonge M. Epidermal growth factor and corneal wound healing. A multicenter study. Cornea. 1992 Jul;11(4):311-4. doi: 10.1097/00003226-199207000-00007.
• Background Pantalon A, Pfister M, Aranha Dos Santos V, Sapeta S, Unterhuber A, Pircher N, Schmidinger G, Garhofer G, Schmidl D, Schmetterer L, Werkmeister RM. Ultrahigh-resolution anterior segment optical coherence tomography for analysis of corneal microarchitecture during wound healing. Acta Ophthalmol. 2019 Aug;97(5):e761-e771. doi: 10.1111/aos.14053. Epub 2019 Feb 14.
• Background Netto MV, Mohan RR, Ambrosio R Jr, Hutcheon AE, Zieske JD, Wilson SE. Wound healing in the cornea: a review of refractive surgery complications and new prospects for therapy. Cornea. 2005 Jul;24(5):509-22. doi: 10.1097/01.ico.0000151544.23360.17.
• Background Moshirfar M, West WB Jr, Milner DC, McCabe SE, Ronquillo YC, Hoopes PC. Delayed Epithelial Healing with Corneal Edema and Haze After Photorefractive Keratectomy Using Intraoperative Mitomycin C. Int Med Case Rep J. 2021 Dec 24;14:863-870. doi: 10.2147/IMCRJ.S342774. eCollection 2021.
• Background Mohan RR, Hutcheon AE, Choi R, Hong J, Lee J, Mohan RR, Ambrosio R Jr, Zieske JD, Wilson SE. Apoptosis, necrosis, proliferation, and myofibroblast generation in the stroma following LASIK and PRK. Exp Eye Res. 2003 Jan;76(1):71-87. doi: 10.1016/s0014-4835(02)00251-8.
• Background Meduri A, Aragona P, Grenga PL, Roszkowska AM. Effect of basic fibroblast growth factor on corneal epithelial healing after photorefractive keratectomy. J Refract Surg. 2012 Mar;28(3):220-3. doi: 10.3928/1081597X-20120103-02. Epub 2012 Jan 9.
• Background McKown RL, Coleman Frazier EV, Zadrozny KK, Deleault AM, Raab RW, Ryan DS, Sia RK, Lee JK, Laurie GW. A cleavage-potentiated fragment of tear lacritin is bactericidal. J Biol Chem. 2014 Aug 8;289(32):22172-82. doi: 10.1074/jbc.M114.570143. Epub 2014 Jun 18.
• Background Klenkler B, Sheardown H, Jones L. Growth factors in the tear film: role in tissue maintenance, wound healing, and ocular pathology. Ocul Surf. 2007 Jul;5(3):228-39. doi: 10.1016/s1542-0124(12)70613-4.
• Background Kaji Y, Obata H, Usui T, Soya K, Machinami R, Tsuru T, Yamashita H. Three-dimensional organization of collagen fibrils during corneal stromal wound healing after excimer laser keratectomy. J Cataract Refract Surg. 1998 Nov;24(11):1441-6. doi: 10.1016/s0886-3350(98)80164-8.
• Background Li J, Lam CS, Yu M, Hess RF, Chan LY, Maehara G, Woo GC, Thompson B. Quantifying sensory eye dominance in the normal visual system: a new technique and insights into variation across traditional tests. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6875-81. doi: 10.1167/iovs.10-5549. Epub 2010 Jul 7.
• Background Legault G. The state of refractive surgery in the U.S. Army. Presented at: Military Refractive Safety and Standards Symposium; January 7-10, 2019; San Diego, CA
• Background Leccisotti A. Mitomycin C in photorefractive keratectomy: effect on epithelialization and predictability. Cornea. 2008 Apr;27(3):288-91. doi: 10.1097/ICO.0b013e31815c5a51.
• Background Laurie GW, Wang N, Raab RW, McKown RL. NFAT/mTOR signaling and downstream promotion of MUC16 expression by lacrimal prosecretory mitogen lacritin. Investigative Ophthalmology & Visual Science. 2006 May 1;47(13):1606-.
• Background Lau JJ, Thach AB, Burden JH, Ward TP, Hshieh PB, Hollifield RD. Eye injuries in the U.S. Armed Forces. Mil Med. 2000 Sep;165(9):683-6.
• Background Hofmeister EM, Bishop FM, Kaupp SE, Schallhorn SC. Randomized dose-response analysis of mitomycin-C to prevent haze after photorefractive keratectomy for high myopia. J Cataract Refract Surg. 2013 Sep;39(9):1358-65. doi: 10.1016/j.jcrs.2013.03.029. Epub 2013 Jul 3.
• Background Hofmeister E. The state of refractive surgery in the U.S. Navy. Presented at: Military Refractive Safety and Standards Symposium; January 7-10, 2019; San Diego, CA
• Background Heier JS, Enzenauer RW, Wintermeyer SF, Delaney M, LaPiana FP. Ocular injuries and diseases at a combat support hospital in support of Operations Desert Shield and Desert Storm. Arch Ophthalmol. 1993 Jun;111(6):795-8. doi: 10.1001/archopht.1993.01090060083028.
• Background Hegarty DM, Carroll JR, Nguyen D, Halls VS, Robbins DI, Price TJ, Dussor G, Aicher SA. Resveratrol increases tear production and ocular pain after corneal abrasion in male, but not female, rats using a photorefractive keratectomy model. Exp Eye Res. 2022 Dec;225:109281. doi: 10.1016/j.exer.2022.109281. Epub 2022 Oct 18.
• Background Gipson LK, Joyce NC. Anatomy and Cell Biology of the Cornea, Superficial Limbus and Conjunctiva. In: Albert DM ed. Principles and Practice of Ophthalmology third ed. Philadelphia: Saunders; 2008:423-40
• Background Georgiev GA, Gh MS, Romano J, Dias Teixeira KL, Struble C, Ryan DS, Sia RK, Kitt JP, Harris JM, Hsu KL, Libby A, Odrich MG, Suarez T, McKown RL, Laurie GW. Lacritin proteoforms prevent tear film collapse and maintain epithelial homeostasis. J Biol Chem. 2021 Jan-Jun;296:100070. doi: 10.1074/jbc.RA120.015833. Epub 2020 Nov 21.
• Background Gensheimer MW, Davies MB, Ellis LC, Chou CE, Cousineau-Krieger UC, Corsini MJ, Caldwell LC, Shackelford CS. Eye trauma: Initial care (cpg id: 03). Joint Trauma System Clinical Practice Guideline. 2021. https://jts.amedd.army.mil/assets/docs/cpgs /Eye_Trauma_Initial_Care_01_Jun_2021_ID03.pdf. Accessed November 1, 2022.
• Background Gallagher EJ, Bijur PE, Latimer C, Silver W. Reliability and validity of a visual analog scale for acute abdominal pain in the ED. Am J Emerg Med. 2002 Jul;20(4):287-90. doi: 10.1053/ajem.2002.33778.
• Background Fujii A, Morimoto-Tochigi A, Walkup RD, Shearer TR, Azuma M. Lacritin-induced secretion of tear proteins from cultured monkey lacrimal acinar cells. Invest Ophthalmol Vis Sci. 2013 Apr 5;54(4):2533-40. doi: 10.1167/iovs.12-10394.
• Background Fowler WC, Chang DH, Roberts BC, Zarovnaya EL, Proia AD. A new paradigm for corneal wound healing research: the white leghorn chicken (Gallus gallus domesticus). Curr Eye Res. 2004 Apr;28(4):241-50. doi: 10.1076/ceyr.28.4.241.27837.
• Background Fogla R, Luthra G, Chhabra A, Gupta K, Dalal R, Khamar P. Preferred practice patterns for photorefractive keratectomy surgery. Indian J Ophthalmol. 2020 Dec;68(12):2847-2855. doi: 10.4103/ijo.IJO_2178_20.
• Background Feng MM, Baryla J, Liu H, Laurie GW, McKown RL, Ashki N, Bhayana D, Hutnik CM. Cytoprotective effect of lacritin on human corneal epithelial cells exposed to benzalkonium chloride in vitro. Curr Eye Res. 2014 Jun;39(6):604-10. doi: 10.3109/02713683.2013.859275. Epub 2014 Jan 8.
• Background Farjo AA, Brumm MV, Soong HK. Corneal Anatomy, Physiology and Wound Healing. In: Yanoff M, Duker JS eds, Ophthalmology fourth ed. London: Elsevier; 2014:163-7
• Background Fantes FE, Hanna KD, Waring GO 3rd, Pouliquen Y, Thompson KP, Savoldelli M. Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys. Arch Ophthalmol. 1990 May;108(5):665-75. doi: 10.1001/archopht.1990.01070070051034.
• Background Efraim Y, Chen FYT, Cheong KN, Gaylord EA, McNamara NA, Knox SM. A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration. Cell Rep. 2022 Aug 30;40(9):111307. doi: 10.1016/j.celrep.2022.111307.
• Background Durrie DS, Wolsey D, Thompson V, Assang C, Mann B, Wirostko B. Ability of a new crosslinked polymer ocular bandage gel to accelerate reepithelialization after photorefractive keratectomy. J Cataract Refract Surg. 2018 Mar;44(3):369-375. doi: 10.1016/j.jcrs.2018.01.018.
• Background DeLoach LJ, Higgins MS, Caplan AB, Stiff JL. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg. 1998 Jan;86(1):102-6. doi: 10.1097/00000539-199801000-00020.
• Background Cockerham GC, Lemke S, Rice TA, Wang G, Glynn-Milley C, Zumhagen L, Cockerham KP. Closed-globe injuries of the ocular surface associated with combat blast exposure. Ophthalmology. 2014 Nov;121(11):2165-72. doi: 10.1016/j.ophtha.2014.06.009. Epub 2014 Aug 11.
• Background Blanch RJ, Kerber MT, Gensheimer WG. Deployed ophthalmic workload in support of US and NATO operations in Afghanistan. BMJ Mil Health. 2021 Dec;167(6):408-412. doi: 10.1136/bmjmilitary-2019-001379. Epub 2020 Mar 5.
• Background Buffault J, Zeboulon P, Liang H, Chiche A, Luzu J, Robin M, Rabut G, Labetoulle M, Labbe A, Baudouin C. Assessment of corneal epithelial thickness mapping in epithelial basement membrane dystrophy. PLoS One. 2020 Nov 25;15(11):e0239124. doi: 10.1371/journal.pone.0239124. eCollection 2020.
• Background Blake CR, Cervantes-Castaneda RA, Macias-Rodriguez Y, Anzoulatous G, Anderson R, Chayet AS. Comparison of postoperative pain in patients following photorefractive keratectomy versus advanced surface ablation. J Cataract Refract Surg. 2005 Jul;31(7):1314-9. doi: 10.1016/j.jcrs.2004.11.046.
• Background Begley C, Caffery B, Chalmers R, Situ P, Simpson T, Nelson JD. Review and analysis of grading scales for ocular surface staining. Ocul Surf. 2019 Apr;17(2):208-220. doi: 10.1016/j.jtos.2019.01.004. Epub 2019 Jan 14.
• Background Barrientez B, Nicholas SE, Whelchel A, Sharif R, Hjortdal J, Karamichos D. Corneal injury: Clinical and molecular aspects. Exp Eye Res. 2019 Sep;186:107709. doi: 10.1016/j.exer.2019.107709. Epub 2019 Jun 22.
• Background Bandeira F, Yusoff NZ, Yam GH, Mehta JS. Corneal re-innervation following refractive surgery treatments. Neural Regen Res. 2019 Apr;14(4):557-565. doi: 10.4103/1673-5374.247421.
• Background Ashby BD, Garrett Q, Willcox MDP. Corneal injuries and wound healing - review of processes and therapies. Austin J Clin Ophthalmol. 2014;1(4): 1017.
• Background Andreotti G, Lange JL, Brundage JF. The nature, incidence, and impact of eye injuries among US military personnel: implications for prevention. Arch Ophthalmol. 2001 Nov;119(11):1693-7. doi: 10.1001/archopht.119.11.1693.
• Background Amparo F, Schaumberg DA, Dana R. Comparison of Two Questionnaires for Dry Eye Symptom Assessment: The Ocular Surface Disease Index and the Symptom Assessment in Dry Eye. Ophthalmology. 2015 Jul;122(7):1498-503. doi: 10.1016/j.ophtha.2015.02.037. Epub 2015 Apr 8.

Drugs

Indications