12/3/2016 1 Options and Outcomes in the Management of Corneal Limbal Stem Cell Deficiency The University of California, San Francisco Ophthalmology Update 2016 San Francisco, CA December 2-3, 2016 Anthony J. Aldave, M.D. Professor of Ophthalmology Chief, Cornea and Uveitis Division The Jules Stein Eye Institute The University of California, Los Angeles Disclosure Anthony J. Aldave, M.D. •Consultant (ad hoc) •5AM Ventures •Avellino Laboratories •W. L. Gore & Associates •Noveome Biotherapeutics (Stemnion) •Sun Ophthalmics •Research Funding •National Eye Institute •Speaker’s Bureau •Avellino Laboratories Management of Bilateral LSCD Lecture Outline • Keratolimbal allografts • Oral mucosal epithelial autografts • Keratoprostheses
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Options and Outcomes in the Management of Corneal Limbal Stem Cell DeficiencyThe University of California, San FranciscoOphthalmology Update 2016San Francisco, CADecember 2-3, 2016Anthony J. Aldave, M.D.Professor of OphthalmologyChief, Cornea and Uveitis DivisionThe Jules Stein Eye InstituteThe University of California, Los Angeles
Disclosure Anthony J. Aldave, M.D.•Consultant (ad hoc)•5AM Ventures•Avellino Laboratories•W. L. Gore & Associates•Noveome Biotherapeutics (Stemnion)•Sun Ophthalmics
Management of Bilateral LSCDKeratolimbal Allografts Indications• All 26 studies were noncomparative case series
•No randomized clinical trials
• 31% (8/26) of studies surveyed bilateral severe or total LSCD alone
•Keratolimbal allograft (KLAL) with systemic immunosuppression in 75% (6/8)
• Chemical or thermal burn (n = 67)
• Aniridia (n = 40)
• Stevens-Johnson syndrome (n = 27)
Cauchi PA, Ang GS, Azuara-Blanco A, Burr JM. A systematic literature review of surgical interventions for limbal stem cell deficiency in humans. Am J Ophthalmol. 2008;146:251-259.
Management of Bilateral LSCDKeratolimbal Allografts Vision• Improvement in CDVA > 2 Snellen lines
•56% (14/25) of eyes1
•67% (10/15) of eyes2
•81% (13/16) of eyes3
•90% (9/10) of eyes4
•Not specified in 4 of the 8 studies5
1Holland EJ. Epithelial transplantation for the management of severe ocular surface disease. Trans Am Ophthalmol Soc. 1996;94:677-743. 2Inatomi T, Nakamura T, Koizumi N, et al. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol. 2006 ;141(2):267-275.3Tsai RJ, Tseng SC. Human allograft limbal transplantation for corneal surface reconstruction. Cornea. 1994 ;13:389-400. 4Ivekovic R, Tedeschi-Reiner E, Novak-Laus K, Andrijevic-Derk B, Cima I, Mandic Z. Limbalgraft and/or amniotic membrane transplantation in the treatment of ocular burns. Ophthalmologica. 2005;219:297-302.5Cauchi PA, Ang GS, Azuara-Blanco A, Burr JM. A systematic literature review of surgical interventions for limbal stem cell deficiency in humans. Am J Ophthalmol. 2008;146:251-259.
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Solomon A, Ellies P, Anderson DF, TouhamiA, GrueterichM, Espana EM, Ti SE, Goto E, Feuer WJ, Tseng SC. Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency. Ophthalmology. 2002;109:1159-66.
Management of Bilateral LSCDKeratolimbal Allografts Survival
Ilari L, Daya SM. Long-term outcomes of keratolimbalallograft for the treatment of severe ocular surface disorders. Ophthalmology. 2002;109:1278-84.
Management of Bilateral LSCDKeratolimbal Allografts Survival
Han ES, Wee WR, Lee JH, Kim MK. Long-term outcome and prognostic factor analysis for keratolimbal allografts. Graefes Arch Clin Exp Ophthalmol. 2011;249:1697-704.
Management of Bilateral LSCDKeratolimbal Allografts Survival
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Holland EJ, MogilishettyG, Skeens HM, Hair DB, Neff KD, Biber JM, Chan CC. Systemic immunosuppression in ocular surface stem cell transplantation: results of a 10-year experience. Cornea. 2012;31(6):655-61.
Management of Corneal LSCDOral Mucosal Epithelial Autograft
Nishida K, Yamato M, Hayashida Y, et al. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med. 2004;351:1187-96.
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Inatomi T, Nakamura T, Koizumi N, Sotozono C, Yokoi N, Kinoshita S. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol. 2006;141:267-275.
Satake Y, Higa K, Tsubota K, Shimazaki J. Long-term outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology. 2011;118: 1524-30.
Management of Bilateral LSCDBoston Keratoprosthesis Indications68 of 173 Procedures
Management of Bilateral LSCDBoston Keratoprosthesis Visual Acuity
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Management of Bilateral LSCDComparative Visual Outcomes• Keratolimbal allografts
•Post-op VA > 20/200 in 44% of eyes1,2
• COMET•Pre-op VA > 20/200 in 0% of eyes•Post-op VA > 20/200 in 27% of eyes at 3-34 months3
• Boston keratoprosthesis•Pre-op VA > 20/200 in 7% of eyes•Post-op VA > 20/200 in 77%, 88% and 86% of eyes at 1, 3 and 5 years
1. Shi W, Gao H, Wang T, et al. Combined penetrating keratoplasty and keratolimbalallograft transplantation in comparison with corneoscleral transplantation in the treatment of severe eye burns. Clin Experiment Ophthalmol 2008;36:501–7.
2. Solomon A, Ellies P, Anderson DF, et al. Long-term outcome of keratolimbalallograft with or without penetrating keratoplasty for total limbalstem cell deficiency. Ophthalmology 2002;109:1159–66.3. Inatomi T, Nakamura T, Koizumi N, Sotozono C, Yokoi N, Kinoshita S. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J
Ophthalmol. 2006;141:267-275.
Management of LSCDBoston Keratoprosthesis Retention
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Length of Follow-up (Months)0 24 48 72 96 120
LSCD Non-LSCD
Management of LSCDBoston Kpro vs KLAL Retention vs Survival
Solomon A, Ellies P, Anderson DF, Touhami A, Grueterich M, Espana EM, Ti SE, Goto E, Feuer WJ, Tseng SC. Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency.Ophthalmology. 2002;109:1159-66.
Cum
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LSCD Non-LSCD
Management of LSCDBoston Kpro vs KLAL Retention vs Survival
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Length of Follow-up (Months)
0 24 48 72 96 120
LSCD Non-LSCD
Ilari L, Daya SM. Long-term outcomes of keratolimbal allograft for the treatment of severe ocular surface disorders. Ophthalmology. 2002;109:1278-84.
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Management of LSCDBoston Kpro vs KLAL Retention vs Survival
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Length of Follow-up (Months)
0 24 48 72 96 120
LSCD Non-LSCD
Han ES, Wee WR, Lee JH, Kim MK. Long-term outcome and prognostic factor analysis for keratolimbal allografts. Graefes Arch Clin Exp Ophthalmol. 2011 Nov;249(11):1697-704.
Management of LSCDBoston Kpro vs COMET Retention vs Survival
Cum
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of R
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ntio
n
0.0
0.2
0.4
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0.8
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Length of Follow-up (Months)
0 24 48 72 96 120
LSCD Non-LSCD
Satake Y, Higa K, Tsubota K, Shimazaki J. Long-term outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology. 2011;118: 1524-30.
Management of LSCDBoston Keratoprosthesis Complications
Management of LSCDBoston Keratoprosthesis Complications
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Satake Y, Higa K, Tsubota K, Shimazaki J. Long-term outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology. 2011;118: 1524-30.
• Boston keratoprosthesis•Provides superior visual outcomes when compared to the published literature on allogenic keratolimbal and oral mucosal epithelial transplantation
Management of Bilateral LSCDConclusions Visual Outcomes
• Boston keratoprosthesis•Retention rate at 5 years is higher than survival rate of keratolimbal allografts and oral mucosal epithelial autografts
Management of Bilateral LSCDConclusions Retention
• Boston keratoprosthesis•Avoids expense and risks associated with systemic immunosuppression
•Only complication significantly more common in eyes with LSCD compared to eyes without is persistent epithelial defect
Management of Bilateral LSCDConclusions Complications
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• The Boston keratoprosthesis is the evidence-based procedure of choice for managing bilateral limbal stem cell deficiency
Management of Bilateral LSCDConclusions Thank You for Your Attention!
