Basic InvestigationCorneal Stromal Regeneration Therapy for Advanced Keratoconus: Long-term Outcomes at 3 YearsEl Zarif, Mona OD, MSc*,†,‡,§; Alió, Jorge L. MD, PhD, FEBOphth¶,†; Alió del Barrio, Jorge L. MD, PhD, FEBOS-CR¶,†; Abdul Jawad, Karim BSc*; Palazón-Bru, Antonio PhD‖; Abdul Jawad, Ziad OD*; De Miguel, María P. PhD**; Makdissy, Nehman PhD§ Author Information *Lebaneese university Hadath: EDST of Biotechnology, Optica General, Saida, Lebanon; †Division of Ophthalmology, Universidad Miguel Hernández University, Alicante, Spain; ‡Lebaneese university Hadath: EDST of Biotechnology, Doctoral School of Sciences and Technology, Lebanese University, Hadath, Lebanon; §GSBT Genomic Surveillance and Biotherapy Team, Faculty of Sciences, Lebanese University, Hadath, Lebanon. ¶Cornea, Cataract and Refractive Surgery Unit, Vissum Instituto Oftalmologico de Alicante, Grupo Miranza, Alicante, Spain; ‖Department of Clinical Medicine, Miguel Hernández University, Alicante, Spain; and **Cell Engineering Laboratory, IdiPAZ, La Paz Hospital Health Research Institute, Madrid, Spain. Correspondence: Jorge L. Alió, MD, PhD, FEBOphth, Cornea, Cataract and Refractive Surgery Unit, Vissum Instituto Oftalmologico de Alicante, Vissum, Calle Cabañal, 1, 03016 Alicante, Spain (e-mail: [email protected]). Supported by Optica General, Saida Lebanon, and Vissum ophthalmological institute of Alicante, Spain, and, in part, by the Red Temática de Investigación Cooperativa en Salud (RETICS), reference number RD16/0008/0012, by the Instituto Carlos III—General Sudirection of Networks and Cooperative Investigation Centers (R&D&I National Plan 2008–2011), and by the European Regional Development Fund (Fondo Europeo de Desarrollo Regional FEDER). The authors have no conflicts of interest to disclose. J. L. Alió: principal investigator, principal surgeon, study concept and design, analysis and interpretation of data, writing and critical revision of the manuscript, statistical revision, and supervision. M. El Zarif: coprincipal investigator, clinical and monitor director of the study, study concept and design, data collecting, analysis and interpretation of data, writing, and critical revision of the manuscript, statistical revision, and supervision. J. L. Alió Del Barrio: second surgeon and critical correction of the manuscript. K. A. Jawad: analysis, interpretation, and editing of the data and writing the manuscript. A. Palazón-Bru: statistical analysis and the corresponding data editing. Z. A. Jawad: data collecting, processing, and administration of the study. M. P. de Miguel: biological processing. N. Makdissy: stem cell therapy processing. Cornea: June 2021 - Volume 40 - Issue 6 - p 741-754 doi: 10.1097/ICO.0000000000002646 Buy Metrics Abstract Purpose: To report the 3-year clinical outcomes of corneal stromal cell therapy consisting of the intrastromal implantation with autologous adipose-derived adult stem cells (ADASCs), and decellularized or ADASC-recellularized human donor corneal laminas in advanced keratoconus. Methods: Fourteen patients were enrolled in 3 experimental groups. Group 1 (G-1) patients underwent implantation of ADASCs alone (3 × 106 cells/1 mL) (n = 5). Group 2 (G-2) patients received a 120-μm decellularized corneal stroma lamina (n = 5). Group 3 (G-3) patients received a 120-μm lamina recellularized with ADASCs (1 × 106 cells/1 mL) (n = 4). ADASCs were obtained by elective liposuction. Implantation was performed into a femtosecond pocket under topical anesthesia. Results: At 3 years, a significant improvement of 1 to 2 logMAR lines in uncorrected distance visual acuity was observed in all groups. A statistically significant decrease in corrected distance visual acuity was obtained in G-2 and G-3 (P < 0.001) when compared with that of G-1. Rigid contact lens distance visual acuity showed a statistically significant worsening in G-2 (P < 0.001) compared with that of G-1. A statistically significant increase in central corneal thickness was observed in G-2 (P = 0.012) and G-3 (P < 0.001); in the Scheimpflug corneal topography, the thinnest point was observed in G-2 (P = 0.007) and G-3 (P = 0.001) when compared with that of G-1. Conclusions: Intrastromal implantation of ADASCs and decellularized or ADASC-recellularized human corneal stroma laminas did not have complications at 3 years. The technique showed a moderate improvement in (uncorrected distance visual acuity) and (corrected distance visual acuity) in advanced keratoconus. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.