Risk Factors for Graft Failure After Penetrating Keratoplasty: 5-Year Follow-Up From the Corneal Transplant Epidemiological Study

Purpose In this study, we aimed to evaluate the efficacy and safety of systemic immunosuppression with mycophenolate mofetil (MMF) to prevent corneal graft rejection after highrisk penetrating keratoplasty. Methods One hundred and ninety-six consecutive patients who underwent high-risk penetrating keratoplasty defined as the presence of deep vascularization in more than two quadrants, keratouveitis, emergency keratoplasties, and retransplantations were enrolled in the study. Ninety-eight prospectively followed up patients were treated with MMF [with dose adjustment based on mycophenolic acid (MPA) serum concentration], and 98 patients were in the non-MMF-treated retrospectively assessed control group. Results During a mean of 24 months of observation, immune reactions occurred in eight cases (8 %) and graft rejection with subsequent graft failure occurred in three cases (3 %) in the MMF group. In the control group, graft rejection occurred in 76 cases (78 %) and failure due to graft rejection occurred in 30 cases (31 %). Kaplan-Meier analysis demonstrated that 93 % of the grafts in the MMF-treated group and 47 % in the control group showed no immune rejection (p<0.01, log-rank test) after a year. Cox regression analysis proved that MMF treatment decreased the risk of graft rejection 11 times (RR=11, 95.0 % CI 4.8-25, p<0.0001). Among 98 MMFtreated patients, 13 had gastric discomfort, three developed leucopenia, and two had anemia that resolved after MMF dose reduction. Conclusions MMF treatment after high risk penetrating keratoplasty is safe and reduces the incidence of immune graft rejection and graft failure. Side effects were rare and reversible in all but one case.

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“…The literature shows that about 33 to 46 % of repeated grafts fail in 2 years of follow-up [26,[28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Systemic immunosuppression with mycophenolate mofetil to prevent corneal graft rejection after high risk penetrating keratoplasty: a 2‐year follow‐up study

Major

Izdebska

Lao

et al. 2015

Acta Ophthalmologica

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“…1 Prior surgical intervention or inflammatory disease, including prior rejection and failure, also poses a higher risk for graft rejection. [1][2][3]9 Inflammatory diseases such as herpetic, interstitial, or traumatic keratitis carry a high risk for endothelial rejection. 9 It is thought that these previous inflammatory episodes may alter the distribution of immune competent cells, which then may be present post-transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…1 A 5-year followup of the Corneal Transplant Epidemiological Study reported that allograft rejection caused graft failure in 17.8% of the 107 failed cornea transplants. 2 Thirty years earlier, Arentsen noted that 42.2% of graft failures were caused by allograft rejection, followed secondly by factors related to uncontrolled glaucoma (19.5%). 3 Localized nonocular infections have been anecdotally known to be associated with corneal graft reactions.…”

Section: Introductionmentioning

confidence: 99%

Corneal allograft reaction associated with nonocular inflammation

Vora¹,

Ciolino²

2014

Digit J Ophthalmol

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SummaryCorneal allograft rejection is known to have many risk factors, including ocular infection and inflammation. Although not reported in the literature, local nonocular inflammation may also have the ability to incite a graft reaction. We report 2 cases, one with dental inflammation and the other with a facial abscess, with simultaneous corneal transplant rejection. Possible pathophysiology and a review of the literature are given.

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“…These large goblet cells can induce opacification of the transparent cornea, leading to reduced or total loss of vision (Miri et al, 2012). Surgical procedures to treat LSCD aim to replace the opacified corneal surface; however, complications, such as graft rejection and subsequent poor tissue survival can arise, even when limbal allografting techniques are employed (Fasolo et al, 2011;Han et al, 2011;Huang et al, 2011). Furthermore, surgical treatment can fail to re-establish the resident stem cell population required for wound repair following insults, resulting in complete restoration of corneal function not being achieved.…”

Section: Introductionmentioning

confidence: 99%

Sphere‐forming cells from peripheral cornea demonstrate a wound‐healing response to injury

Huang

Yoon

Ismail

et al. 2015

Cell Biology International

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The cornea is the initial refractive interface of the eye. Its transparency is critical for clear vision and is maintained by stem cells which also act to repair injury inflicted by external insults, such as chemical and thermal burns. Damage to the epithelium compromises its clarity and can reduce or eliminate the stem cell population, diminishing the ability for self-repair. This condition has been termed "limbal stem cell deficiency"; severe cases can lead to corneal blindness. Sphere-forming cells isolated from peripheral cornea are a potential source of stem and progenitor cells for corneal repair. When provided with appropriate substrate, these spheres have the ability to adhere and for cells to migrate outwards akin to that of their natural environment. Direct compression injury and remote scratch injury experiments were conducted on the sphere cells to gauge their wound healing capacity. Measures of proliferation, differentiation, and migration were assessed by immunohistochemical detection of EdU incorporation, α-smooth muscle actin expression and confocal image analysis, respectively. Both modes of injury were observed to draw responses from the spheres indicating wound healing processes. Direct wounding induced a rapid, but transient increase in expression of α-SMA, a marker of corneal myofibroblasts, followed by a proliferative and increasing migratory response. The spheres were observed to respond to remote injury as entire units, with no directional response seen for targeted repair over the scratch injury area. These results give strength to the future use of these peripheral corneal spheres as transplantable units for the regeneration of corneal tissue.

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Risk Factors for Graft Failure After Penetrating Keratoplasty: 5-Year Follow-Up From the Corneal Transplant Epidemiological Study

Abstract: Penetrating keratoplasty shows an overall positive prognosis in the long-term. However, the probability of graft survival is largely dependent on the preoperative clinical condition and the lack of complications during follow-up.

Cited by 78 publications

References 22 publications

Systemic immunosuppression with mycophenolate mofetil to prevent corneal graft rejection after high risk penetrating keratoplasty: a 2‐year follow‐up study

Systemic immunosuppression with mycophenolate mofetil to prevent corneal graft rejection after high risk penetrating keratoplasty: a 2‐year follow‐up study

Corneal allograft reaction associated with nonocular inflammation

Sphere‐forming cells from peripheral cornea demonstrate a wound‐healing response to injury

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