Repeated Penetrating Keratoplasty:Clinical Outcomes And Graft Features

Corneal blindness is one of the leading causes of blindness in the developing world. Since its first introduction in1906by Zirm, allogeneic penetrating keratoplasty (PKP) has been one of the most commonly-used surgical techniques to treat corneal blindness. Notwithstanding the advantages of easy manipulation, wide range of indications and better visual recovery after surgery, immunological rejection is still the major cause of graft failure. In addition, graft dysfunction has close relationship with many other factors such as the quality of donor, the preservation of donor, the primary diseases of host, surgical manipulation, the size of donor tissue, the time duration of surgery, postoperative complications, and mismatching of ABO blood type and HLA system between donor and recipient.With the elongation of life expectancy and increasing demand for better life quality, the number of patients asking for repeated PKP is gradually rising, accounting for22%-41%of total recipients annually by previous reports. However, previous reports were mainly retrospective study, being inevitable with the bias cause by incomplete records or even record loss. Up till now, no prospective study has been published to compare the primary causes, visual and clinical outcome, the incidence of immunological rejection, and postoperative complications between patients undergoing repeated PKP and ones with single surgery. Moreover, issues about graft features after repeated surgery, such as graft thickness and cellular density, and their correlation with graft outcome also require to be addressed. The present study is designed as prospective, controlled, comparative analysis, and is subjected to investigate and compare the clinical outcome of repeated PKP therapy and one-time PKP therapy on the primary disease causes, visual outcome, postoperative complications and levels of various optometric indexes, in order to provide a better theoretic guidance for the repeated PKP recipients.Part ⅠAnalysis of clinical efficacy after repeated PKPObjective:To analyze the clinical features of patients undergoing repeat PKP, and evaluate their clinical outcome.Methods:The patients undergoing repeated PKP from October,2010to January,2013and meeting the inclusion criteria were enrolled. Analysis was performed regarding the primary cause of the first surgery, the size of donor and host bed in the repeated surgery, time duration of repeated surgery, complications during and after operation, and BCVA and optometric status at the last follow-up.Results:49patients(49eyes),29males and20females, were enrolled in the study, with an average age of (47.8+17.7) years old. The range of preoperative VA was LP-FC/BE. The diagnosis before the first PKP surgery included fungal keratitis in11eyes, bullous keratopathy in10eyes, ocular trauma in9eyes, herpes simplex keratitis in8eyes, corneal dystrophy in8eyes, congenital leucoma in2eyes, and iridocorneal endothelial syndrome in1eye. Average size of corneal graft was7.82±0.26mm in the repeated surgery. No complications were encountered during the repeated operation. The average postoperative follow-up time was10.67±months. Postoperative complications included graft rejection in11eyes, graft failure in7eyes, and high ocular pressure in25eyes, among which13eyes developed secondary glaucoma. At the last follow-up, average BCVA, equivalent spherical diopters and cylinder was (0.25±0.17),(-1.47±2.45)D, and (-3.41±1.413)D respectively.Conclusion:Among the patients receiving repeated PKP, those with infectious ocular surface diseases before the first surgery accounts for the largest proportion. High ocular pressure, secondary glaucoma and reject reaction all are the common complication after repeated surgery. Part IIAnalysis on morphological features of corneal graft after repeat PKP by the application of AS-OCT and IVCMObjective:To investigate the morphological features of corneal graft after repeated PKP treatment by the application of AS-OCT and IVCM and explore the cellular variation of graft after surgery.Methods:The patients undergoing repeated PKP from October,2010to January,2013and meeting the inclusion criteria were enrolled. Subjects were required to follow up at lwk,2wks, lmh,2mhs,3mhs,6mhs,9mhs,12mhs,18mhs,21mhs,24mhs after surgery. At each examination time point, AS-OCT and IVCM were performed. The corneal graft thickness and corneal epithelium thickness were measured. Moreover, the morphology and density of corneal epithelial basal layer cells, anterior stroma cells and endothelial cells were analyzed.Results:The study population was the same as the Part I. At lmh postoperatively, the graft thickness was538.67±66.17μm, and it decreased to475.60±60.90μm during1mh to12mhs. However, it increased to509.33±70.29μm during the second year after operation(Χ2=35.21, P=0.000). The changes of corneal epithelium thickness is almost the same (F=2.76, P=0.002). The cellular density of corneal basal epithelium at lmh postoperatively was9072±579cell/mm2, and then it increased to9811±221cell/mm2at12mhs and further decreased to9502±224cell/mm2at24mhs(X2=128.0,P=0.000). In6month after surgery, the regrowth of corneal nerve fibers below the corneal basal epithelium and Bowman’s layer were be observed. The alteration of anterior stromal cell was similar, except that the peak of cellular density after surgery occurred at3mhs (Χ2*=107.69, P=0.000). The density of endothelial cells decreased continuously after surgery, from2765±341cell/mm2at lmh to1302±555cell/mm2at24mhs postoperatively (X2=130.70, P=0.000).Conclusion:The corneal graft thickness increased after one year postoperatively, along with continuously decreased density of corneal endothelial cells, indicating that the graft function tended to decline at one year after repeated PKP.Part ⅢComparison on morphological features of corneal graft between recipients with repeated PKP and those undergoing single PKPObjective:to compare the morphological features of corneal graft after repeated PKP and single surgical treatment by the application of AS-OCT and IVCM, and explore the impact of the second surgery on corneal cellular morphology.Methods:The patients undergoing either repeated PKP or single PKP from October,2011to January,2013and meeting the inclusion criteria were enrolled. Subjects were required to follow up at1wk,2wks, lmh,2mhs,3mhs,6mhs,9mhs and12mhs after surgery. At each examination time point, AS-OCT and IVCM were performed. The same clinical parameters were measured and analyzed, just as those in part Ⅱ.Result:36patients (36eyes) with repeated PKP and47ones (47eyes) with single PKP were included in the present study, with an average age of (43.1±16.7) and (46.3±19.1) respectively. Comparisons on corneal graft thickness, cellular density of corneal basal epithelium and anterior stroma between two groups didn’t show any statistically significant differences at each time point after surgery. The analysis on corneal epithelium thickness presented similar results, except thicker corneal epithelium at lmh and3mhs after repeated PKP. The results demonstrated the regeneration of the never fibers in single PKP group were observed in the first three months after surgery, earlier than the repeated PKP group. However, the reduction of endothelial cell density is far quicker in grafts after repeated PKP than those with single PKP. The comparison between them showed statistical significance from3mhs postoperatively and then on (single PKP:2946±165cell/mm2(3mhs),2948±221cell/mm2(6mhs), 2621±399cell/mm2(9mhs),2664±553cell/mm2(12mhs); repeated PKP:2370±457cell/mm2(3mhs),2127±560cell/mm2(6mhs),1993±449cell/mm2(9mhs),1650±453cell/mm2(12mhs); all P value<0.001.Conclusion:Compared with single PKP, more severe edematous corneal epithelium was found in ones with repeated PKP. Furthermore, the reduction of endothelial cell density in the repeated PKP group is faster, indicating that more intensive attention should be paid on the alteration of endothelial cells in patient with repeat PKP.