RESUMEN
PURPOSE: This study evaluated 1-year safety and efficacy outcomes of corneal stroma cell therapy. Therapy consisted of implanting autologous adipose-derived adult stem cells (ADASc) with or without sheets of decellularized donor human corneal stroma within the stroma of patients with advanced keratoconus. DESIGN: This was a prospective interventional non-randomized series of cases. METHODS: Fourteen consecutive patients were selected and divided into 3 experimental groups. Group A patients underwent implantation of autologous ADASc alone (3 × 106 cells/1 mL) (n = 5). Group B patients received decellularized donor 120-µm-thick corneal stroma lamina alone (n = 5). Group C patients had implantation of recellularized donor lamina with 1 × 106 autologous ADASc plus another 1 × 106 cells/1 mL at the time of the surgery (n = 4). Autologous ADASc were obtained by elective liposuction. Implantation was performed in the corneal stroma through a femtosecond-assisted 9.5-mm diameter lamellar dissection with the patient under topical anesthesia. Twelve months of follow-up data are presented. RESULTS: No complications were observed during the 1-year follow-up, and full corneal transparency was recovered within 3 months in all patients. No patient lost lines of visual acuity. Corrected distance visual acuity improved 0.231, 0.264, and 0.094 Snellen lines in groups 1, 2, and 3, respectively. In group 1, refractive parameters showed an overall stability, whereas in groups 2 and 3, sphere improved 2.35 diopter (D) and 0.625 D, respectively. Anterior keratometry remained stable (group 1) and improved in groups 2 and 3 (mean improvement of 2D). Corneal aberrometry improved significantly. In optical coherence tomography scans, corneal thickness showed a mean improvement of 14.5 µm (group 1) and 116.4 µm (groups 2 and 3) in the central thickness, and new collagen production was observed at the surgical plane (group 1). Confocal biomicroscopy confirmed the host recellularization of the implanted laminas. CONCLUSIONS: Intrastromal implantation of autologous ADASc and decellularized human corneal stroma did not show complications at 1 year of follow-up and were moderately effective for the treatment of advanced keratoconus. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Sustancia Propia/cirugía , Queratocono/terapia , Procedimientos Quirúrgicos Oftalmológicos/métodos , Trasplante de Células Madre/métodos , Agudeza Visual , Adulto , Sustancia Propia/citología , Topografía de la Córnea , Femenino , Estudios de Seguimiento , Humanos , Queratocono/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: This phase 1 study seeks to preliminarily evaluate the safety and efficacy of decellularized human corneal stromal lamina transplantation with or without autologous adipose-derived adult stem cell recellularization within the corneal stroma of patients with advanced keratoconus. DESIGN: Phase 1 clinical trial. METHODS: Femtosecond-assisted 120-µm thickness and 9-mm diameter laminas were obtained from the anterior stroma of human donor corneas and decellularized with a sodium dodecyl sulfate solution. Autologous adipose-derived adult stem cells were obtained by elective liposuction and cultured onto both sides of the lamina. Five patients received the decellularized lamina alone and 4 patients the recellularized lamina into a femtosecond-assisted 9.5-mm diameter lamellar pocket under topical anesthesia. The total duration of follow-up was 6 months. RESULTS: No case showed clinical haze or scarring by month 3. Six months after surgery, patients showed a general improvement of all visual parameters, with a mean unaided visual acuity from 0.109 to 0.232 (P = .05) and corrected distance visual acuity from 0.22 to 0.356 (P = .068). Refractive sphere improved in all patients (from -4.55 diopters [D] to -2.69 D; P = .017), but refractive cylinder remained stable (from -2.83 to -2.61; P = .34). An improvement tendency of all anterior keratometric values was observed. A mean improvement of 120 µm in all thickness parameters was confirmed (P = .008), as well as an improvement in the spherical aberration (P = .018), coma (P = .23) and total higher order aberrations (P = .31). No significant differences among groups were detected. CONCLUSIONS: Decellularized human corneal stromal laminas transplantation seems safe and moderately effective for advanced keratoconus. Potential benefits of its recellularization with autologous adipose-derived adult stem cells remains unclear.
Asunto(s)
Sustancia Propia/patología , Topografía de la Córnea/métodos , Trasplante de Córnea/métodos , Queratocono/cirugía , Trasplante de Células Madre/métodos , Agudeza Visual , Adulto , Células Cultivadas , Paquimetría Corneal , Sustancia Propia/trasplante , Femenino , Estudios de Seguimiento , Humanos , Queratocono/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Refracción Ocular , Índice de Severidad de la Enfermedad , Células Madre/citología , Factores de Tiempo , Tomografía de Coherencia Óptica , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: The aim of this phase 1 study was to preliminarily evaluate the safety and efficacy of autologous adipose-derived adult stem cell (ADASC) implantation within the corneal stroma of patients with advanced keratoconus. METHODS: Five consecutive patients were selected. Autologous ADASCs were obtained by elective liposuction. ADASCs (3 × 10) contained in 1 mL saline were injected into the corneal stroma through a femtosecond-assisted 9.5-mm diameter lamellar pocket under topical anesthesia. Patients were reviewed at 1 day, 1 week, 1, 3, and 6 months postoperatively. Visual function, manifest refraction, slit-lamp biomicroscopy, intraocular pressure, endothelial cell density, corneal topography, corneal optical coherence tomography, and corneal confocal biomicroscopy were recorded. RESULTS: No intraoperative or postoperative complications were recorded, with full corneal transparency recovery within 24 hours. Four patients completed the full follow-up. All patients improved their visual function (mean: 1 line of unaided and spectacle-corrected distance vision and 2 lines of rigid contact lens distance vision). Manifest refraction and topographic keratometry remained stable. Corneal optical coherence tomography showed a mean improvement of 16.5 µm in the central corneal thickness, and new collagen production was observed as patchy hyperreflective areas at the level of the stromal pocket. Confocal biomicroscopy confirmed the survival of the implanted stem cells at the surgical plane. Intraocular pressure and endothelial cell density remained stable. CONCLUSIONS: Cellular therapy of the human corneal stroma in vivo with autologous ADASCs appears to be safe. Stem cells survive in vivo with intrastromal new collagen production. Future studies with larger samples are required to confirm these preliminary results.