Ocular Surface Stem Cell Transplantation Rejection

Ang, Andrea Y.; Chan, Clara C.; Biber, Joseph M.; Holland, Edward J.

doi:10.1097/ico.0b013e318255eac4

Cited by 57 publications

(49 citation statements)

References 24 publications

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“…Acute and chronic episodes of AMR post-KLAL have previously been treated with increased systemic immunosuppression combined with increasing topical and systemic steroids 5 6. Our patient was optimally immunosuppressed with perioperative basiliximab infusions as well as with tacrolimus and mycophenolic acid.…”

Section: Discussionmentioning

confidence: 90%

“…Clinical features of acute KLAL rejection has been previously reported 6. Severe acute rejection presents as moderate to severe pain; intense sectoral or 360° of injection; and/or oedema, haemorrhage, or neovascularisation of the KLAL or living-related conjunctival limbal allograft segments.…”

Section: Differential Diagnosismentioning

confidence: 81%

“…However, even with appropriate systemic immunosuppression, KLAL may be complicated by antibody-mediated rejection (AMR) 5 6. The incidence of AMR among KLAL patients on systemic immunosuppression has been reported to be as high as 24% 5.…”

Section: Introductionmentioning

confidence: 99%

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Intravenous immunoglobulin for antibody-mediated keratolimbal allograft rejection

2015

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A 33-year-old woman with congenital aniridia presented with decreased vision in her right eye. Slit lamp examination revealed diffuse conjunctivalisation of the ocular surface with mild subepithelial fibrosis consistent with aniridic keratopathy secondary to limbal stem cell deficiency. She underwent limbal stem cell transplantation with cadaver donor tissue (keratolimbal allograft (KLAL) surgery) and received systemic immunosuppression. Despite optimal combination immunosuppressive therapy managed by a renal transplant specialist, 2 weeks after the KLAL, the patient developed intractable eye pain, conjunctival injection, dilation of the KLAL graft blood vessels and limbal haemorrhages. There were no epithelial defects noted. Donor-specific antibody testing was positive, and intravenous immunoglobulin therapy was initiated. There was immediate symptomatic and objective improvement. Fifteen months postoperatively, the patient's vision was 20/400 with a stable corneal epithelium and no evidence of inflammation.

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Section: Discussionmentioning

confidence: 90%

Section: Differential Diagnosismentioning

confidence: 81%

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Intravenous immunoglobulin for antibody-mediated keratolimbal allograft rejection

2015

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“…1–3 Severe deficiency of limbal stem cells (LSC), or dysfunction of their local microenvironment, can be a devastating consequence of diverse pathologic insults including congenital aniridia, chemical injury, and Stevens-Johnson syndrome. 4–7 Once the function of the LSCs is sufficiently diminished, patients present clinically with various degrees of corneal conjunctivalization, otherwise known as limbal stem cell deficiency (LSCD). Ultimately, the development of significant pain and permanently disabling visual loss are the unfortunate results of non-healing epithelial defects, progressive neovascularization, and severe stromal scarring.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, keratolimbal allografts (KLAL) utilize cadaver-derived donor limbal tissue and have demonstrated significantly improved visual acuity in patients with bilateral LSCD over several years of follow-up. 4, 5 …”

Section: Introductionmentioning

confidence: 99%

Late Acute Rejection After Allograft Limbal Stem Cell Transplantation

Eslani

Haq

Movahedan

et al. 2017

Cornea

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Purpose To describe the clinical presentation and management of late (>3.0 years) acute graft rejection in keratolimbal allograft (KLAL) recipients. Methods Multicenter, retrospective observational case series. 6 eyes of 6 patients with ocular surface transplant at a mean age of 36.2 years seen at 3 tertiary referral centers for acute graft rejection between 2007 and 2013. Main outcome measures included strength of systemic immunosuppression (SI) at the time of rejection, time to rejection, and clinical presentation of rejection. Results Preoperative diagnoses included total limbal stem cell deficiency (LSCD) due to aniridia (n = 2) or chemical injury (n = 4). Following an initially successful outcome, patients experienced late acute graft rejection at a mean time of 67.8 ± 24.1 months (range: 41 to 98) after KLAL while receiving suboptimal levels of SI due to medication taper (n = 5) or noncompliance (n = 1). Objective findings included an epithelial rejection line (n = 6), edema (n = 2), corneal epithelial irregularities (n = 2), and neovascularization (n = 1). Anti-rejection management consisted of topical corticosteroids (n = 6) and augmentation of SI therapy (n = 5). Conclusion These cases of late acute graft rejection in KLAL patients support the notion that allodonor cells can persist over the long run and remain at risk for immunologic rejection. It further underscores the fact that long-term success with KLAL may require extension of SI beyond the first few years, albeit at lower levels individualized to each patient.

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Long-Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency

Borderie

Ghoubay

Georgeon

et al. 2019

Stem Cells Translational Medicine

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We aimed to evaluate efficiency and safety of transplantation of limbal stem cells (LSC) cultured on human amniotic membrane with no feeders and to compare cultured LSC with limbal tissue transplantation. Thirty eyes with stage III LSC deficiency were treated with autologous (autoLSC) or allogeneic (alloLSC) cultured LSC transplantation (prospective phase II clinical trial; average follow-up time, 72 months) or autologous (autoLT) or allogeneic (alloLT) limbal tissue transplantation (retrospective control group; average follow-up time, 132 months) between 1993 and 2014. The 5-year graft survival defined by absence of recurrence of the clinical signs of limbal deficiency was 71% for autoLSC, 0% for alloLSC, 75% for autoLT, and 33% for alloLT. Visual acuity improved by 9.2 lines for autoLSC and 3.3 lines for autoLT. It decreased by 0.7 lines for alloLSC and 1.9 lines for alloLT. Adverse events were recorded in 1/7 autoLSC, 7/7 alloLSC, 6/8 autoLT, and 8/8 alloLT patients. Corneal epithelial defect was the only adverse event recorded after autoLSC, whereas severe sight-threatening adverse events were recorded in the remaining three groups. Compared with failed grafts, successful grafts featured greater decrease in fluorescein staining, greater superficial vascularization-free corneal area, lower variability of the corneal epithelial thickness, and higher corneal epithelial basal cell density. Autologous cultured LSC transplantation was associated with high long-term survival and dramatic improvement in vision and was very safe. Autologous limbal tissue transplantation resulted in similar efficiency but was less safe. Cadaver allogeneic grafts resulted in low long-term success rate and high prevalence of serious adverse events. STEM CELLS TRANSLATIONAL MEDICINE 2019;8:1230-1241 LESSONS LEARNED• Transplantation of autologous cultured limbal stem cells was associated with high long-term survival, dramatic improvement in vision, and high safety. • Transplantation of autologous limbal tissue resulted in similar efficiency but lower safety.• Cadaver allogeneic grafts resulted in low long-term success rate and high prevalence of serious adverse events. SIGNIFICANCE STATEMENTAutologous cultured limbal stem cell transplantation was associated with high long-term survival, vision improvement, and safety, whereas limbal grafts featured lower safety and allogeneic grafts featured low success rate and serious adverse events.

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Ocular Surface Stem Cell Transplantation Rejection

Cited by 57 publications

References 24 publications

Intravenous immunoglobulin for antibody-mediated keratolimbal allograft rejection

Intravenous immunoglobulin for antibody-mediated keratolimbal allograft rejection

Late Acute Rejection After Allograft Limbal Stem Cell Transplantation

Long-Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency

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