Penetrating keratoplasty for keratoconus: complications and long-term success.

A series of 100 penetrating keratoplasties for keratoconus performed between 1968 abd 1986 were reviewed for long-term results. The mean follow-up was 6.1 years with a range of 4-16 years. The systemic associations and the postoperative complications were analysed. Grafting in cases associated with Down's syndrome had a higher incidence of complications. 93% of grafts remained clear and 81% achieved a final corrected visual acuity of 6/12 or better. 21% of eyes developed a homograft reaction, with 50% of rejection episodes occurring in the first year after operation. Factors associated with higher incidence of rejection included loose sutures, traumatic wound dehiscence, and grafts larger than 8.5 mm. Only three grafts with rejection episodes lost graft clarity, while rejection in the rest was successfully reversed with topical steroid therapy. No relationship was found between donor age and long-term graft clarity.     

Schwerwiegende Wund- und Nahtinsuffizienzen nach perforierender Keratoplastik

BACKGROUND: With regard to penetrating keratoplasty methods to culture corneal donor tissues, microsurgical techniques, HLA typing and understanding of basic mechanisms in inflammation and especially graft rejection, and postoperative treatment schedules have been improved in recent years. This now enables successful penetrating keratoplasty in many more patients than previously performed. However, in rare cases relevant problems in wound closure may appear. PATIENTS AND METHODS: A standardized treatment protocol was applied to 1,253 penetrating keratoplasties performed in a single center. Patients were continuously followed up. Simple leakage after corneal grafting was not further analyzed if conservative treatment or additional sutures achieved sufficient wound closure. In 21 cases, however, the causes of large wound dehiscence after corneal grafting were analyzed. RESULTS: During the first week early problems in suturing penetrating keratoplasty in five patients were associated with the instability of the recipients' corneal stroma (stromal thinning in keratoconus or corneal herpes, suture problems in keratomalacia, active herpes keratitis, corneal burns, or rheumatic diseases). Long-term complications in 16 patients were associated with alcoholism, herpes keratitis, rheumatic disorders or traumatic suture defects. Overall, nine patients lost functionally or even anatomically one eye because of wound dehiscence after corneal grafting. CONCLUSIONS: When penetrating keratoplasty is indicated, special attention should be given to (1) the compliance of the patient, (2) sufficient treatment of herpes keratitis or other infections, (3) adequate immunosuppression in autoimmune corneal inflammation, (4) double running continuous sutures as primary suture with sometimes additional single sutures to stabilize the graft, and (5) surgery in time.     

The results of penetrating keratoplasty for pellucid marginal corneal degeneration

Over a 14-year period from 1974 to 1988, 12 eyes of 11 patients with pellucid marginal corneal degeneration underwent penetrating keratoplasty. Peripheral corneal thinning required a large eccentric graft in each case. Follow-up ranged from one to eight years (mean, three years). One graft failed because of a persistent epithelial defect with keratolysis of the wound. Although endothelial allograft rejection was common, occurring in seven of 11 (64%) clear grafts, no graft failed because of rejection. Other complications included retinal detachment and a bacterial corneal ulcer. Suture erosion and vascularization of the graft were not problems. Postoperative spectacle correction was dispensed an average of 11 months after surgery. Visual acuity in seven patients without amblyopia, retinal disease, or a previous corneal ulcer at the time of spectacle correction ranged from 20/20 to 20/40 (mean, 20/30). Average final keratometric astigmatism in these patients was 2.46 diopters (range, 0.00 to 5.25 diopters). We believe that penetrating keratoplasty offers an excellent surgical result for patients with pellucid marginal corneal degeneration.     

Transplantation of Congenitally Opaque Corneas

Nine transparent grafts in fifteen eyes with congenitally opaque corneas with a one- to ten-year follow-up are described. Patients ranged in age at the time of surgery from two to thirty months. Vision in all but two of the eyes with transparent grafts improved. The operative complications included an exaggerated anterior displacement of the lens-iris diaphragm and difficulty obtaining a water-tight wound closure because of the flaccidity of the infant host tissue. The postoperative complications included a peculiar late-developing glaucoma, graft rejection, infection, and early suture loosening.     

穿透性角膜移植治疗外伤性角膜病变的临床观察

目的:探讨穿透性角膜移植术治疗外伤性角膜病变的临床疗效。方法:对17例外伤性角膜病变施行穿透性角膜移植术,2例行穿透性角膜移植术联合小梁切除术,观察术后角膜植片及视力变化。结果:随访6~18(平均11.2)mo,术后临床症状明显缓解或消失,植片透明率为84%。视力较术前提高,其中矫正视力0.05以上16例;术后继发性青光眼5例,内皮型排斥反应4例。结论:穿透性角膜移植术是治疗外伤性角膜病变的一种有效的手术方式,其主要并发症为继发性青光眼和角膜移植排斥反应。     

Adult keratoplasty: has the prognosis improved in the last 25 years?

Adult keratoplasty outcomes have significantly improved in the past quarter century as a result of new pharmaceuticals, advanced surgical devices, better understanding of what causes graft failure, and targeted techniques for selective replacement of only diseased corneal layers. Prevention and treatment of graft rejection, which has long been a leading cause of graft failure, has improved with the development of innovative topical and systemic immuno-suppressants. New methods for preventing and treating ocular surface complications have been devised, and limbal stem cell grafts have significantly improved management of severe ocular surface disease. Improved intraocular lens designs cause less corneal damage and have increased corneal graft survival. Non-steroidal anti-inflammatory (NSAID) eyedrops and more complete vitrectomies have reduced the incidence of chronic cystoid macular edema, which could prevent eyes with clear grafts from regaining useful vision. Patients with keratoconus or corneal scars can now benefit from advanced anterior lamellar keratoplasty techniques, which reduce the risk of immunologic rejection and endothelial failure, while matching the visual outcomes achieved with penetrating keratoplasty. Patients with endothelial dysfunction can now benefit from advanced endothelial keratoplasty techniques, which provide more rapid visual recovery, minimize induced astigmatism and ocular surface problems, and virtually eliminate the risk of wound rupture from minor trauma. Finally, femtosecond lasers now provide transplant surgeons with a precise tool for creating complex, interlocking corneal incisions that may facilitate wound healing.     

Traumatic wound dehiscence following penetrating keratoplasty

BACKGROUND AND PURPOSE: Blunt ocular trauma to a corneal transplanted eye represents a higher risk for wound rupture at the donor-recipient interface. We have evaluated the causes, clinical characteristics, treatment and outcome, particularly the graft's clarity, in patients with traumatic wound dehiscence after penetrating keratoplasty. METHODS: Between March 1996 and April 2006, over a period of 10 years, 4 patients who had previously undergone successful penetrating keratoplasty and subsequently sustained traumatic wound dehiscence were treated at our department. All eyes underwent primary wound closure with interrupted 10-0 nylon sutures. RESULTS: Over the 10-year period, the incidence of traumatic wound dehiscence in which penetrating keratoplasty was performed was 2.35 % (4 of 170 patients). The ages of our patients at the time of injury were 6, 76, 78 and 39 years. The interval between penetrating keratoplasty and trauma varied from 12 through 16 and 17 to 30 months. All corneal dehiscences occurred at the graft-host junction. All dehiscences were at the temporal-superior quadrant (4 of 4 eyes) and at superior-nasal and temporal quadrants in 3 of 4 eyes. Two eyes that were pseudophakic had lost their implants and required anterior vitrectomy. In one of these patients (a 76-year-old women) delayed-onset expulsive choroidal haemorrhage occurred at the end of surgical repair. Visual outcome was correlated with the force of trauma, previous eye conditions and complications during surgery. All of the resutured grafts retained clarity. CONCLUSION: Traumatic wound dehiscence is a serious and not uncommon complication following penetrating keratoplasty. Despite severe trauma, graft transparency was achieved in all cases and there was no need for regrafting.     

Late traumatic intraocular lens extrusion after penetrating keratoplasty

BACKGROUND: Penetrating keratoplasty places a patient at risk for wound rupture from blunt trauma because the graft-host interface remains weakened for years after the surgery. Violent environments, contact sports, and strenuous activity put patients with compromised corneal structural integrity at high risk of traumatic injury. CASE REPORT: This case report presents a 42-year-old penetrating keratoplasty patient with a history of homelessness, polysubstance abuse, and domestic violence. This patient experienced a ruptured globe at the graft-host junction secondary to a direct blow by a fist, which extruded the intraocular lens from the eye. After emergency wound closure, the graft continued to degrade until bullous keratopathy developed. With little visual recovery potential for this graft, a Gunderson conjunctival flap procedure was implemented to decrease chronic ocular pain. CONCLUSIONS: After penetrating keratoplasty, patients should be periodically reminded of the susceptibility of the graft wound to injury from high-risk activity and violence. Constant use of protective eyewear should be recommended to corneal transplant recipients.     

Traumatic wound dehiscence following penetrating keratoplasty.

Four young male patients with keratoconus had traumatic dehiscence of the surgical wound after penetrating keratoplasty. Two were rendered aphakic by the trauma, and in one patient the lens was dislocated posteriorly. In each case the dehiscence was repaired by resuturing the original corneal graft. Despite marked corneal oedema in the immediate postoperative period all four grafts deturgesced and subsequently cleared. The follow-up has been a minimum of 23 months. We recommend therefore primary resuturing of traumatic wound dehiscence after keratoplasty, anterior vitrectomy if the lens dislodged, and prophylactic antibiotics postoperatively. The clearing of the initially oedematous grafts in each case illustrates the resilience of the corneal endothelium.     

Influence of HLA-A, HLA-B, and HLA-DR matching on rejection of random corneal grafts using corneal tissue for retrospective DNA HLA typing

AIM: To establish if coincidental HLA-A, HLA-B, and HLA-DR tissue matching is associated with a reduced likelihood of corneal graft rejection. METHODS: Organ culture preserved random donor corneas were used for penetrating keratoplasty (PKP). Corneal tissue from all graft recipients and donors or blood samples from recipients after repeated transplantation were obtained in order to perform retrospective molecular HLA typing. A group of 21 recipients with a rejection episode (cases) after corneal transplantation was compared with a control group of non-rejectors (n = 43). 31 graft recipients were considered as high risk patients. The influence of HLA-A, HLA-B, and HLA-DR matching on rejection free graft survival time was analysed with Kaplan-Meyer statistics and Cox regression. RESULTS: A prolonged rejection free survival time was observed in graft recipients with one or two HLA-A matches (log rank test, p = 0.034). This effect was also observed in high risk graft recipients with one or two HLA-DR matches (log rank test, p = 0.030). CONCLUSIONS: Coincidental HLA-A and HLA-DR matches were observed and associated with a prolonged rejection free survival time in the total group and in the high risk group, respectively. These results support the beneficial effect of prospective HLA-A and HLA-DR typing upon corneal graft survival.     

Topical Cyclosporin A in the treatment of acute graft rejection: a randomized controlled trial

Background:  Corneal graft rejection is the commonest cause of graft failure. Currently, intensive topical steroid is the treatment for graft rejection. We hypothesized that the use of topical Cyclosporin A (CsA) 0.05%, specifically Restasis (Allergan) in addition to intensive steroids would aid in the reversal and treatment of endothelial graft rejection.
Methods:  In a randomized double masked control study, we recruited 108 patients with acute endothelial graft rejection. They were randomized to two groups. The first group received intensive prednisolone acetate and placebo. The second group received intensive prednisolone acetate and Restasis.
Results:  There was no difference between the baseline characteristics for the two groups. Nine out of 54 in the placebo group and five out of 54 (16.7% vs. 9.2% P  = 0.23) in the treatment group were exited from the study because of worsening signs despite treatment. No significant difference was found between the two groups for time to reversal and resolution. Side-effects of the treatment include increased intraocular pressure and punctate epithelial erosions. These changes most likely relate to the use of intensive prednisolone acetate.
Conclusion:  The use of commercially available CsA as an adjunct to topical steroids does not appear to improve the outcome of graft rejection.     

Effects of penetrating keratoplasty rejection on the endothelium of the donor cornea and the recipient peripheral cornea

PURPOSE: To determine the effects of penetrating keratoplasty rejection on the recipient endothelium. METHODS: Twenty transplanted corneas of 20 keratoconus patients were enrolled in this study. Ten of the corneas had undergone allograft rejection and the other 10 grafts had an uneventful postsurgical course. The endothelium of the donor cornea and the endothelium of the recipient peripheral cornea were evaluated by wide-field specular microscopy. RESULTS: The transplanted corneas that underwent allograft rejection showed a marked decrease in endothelial cell density not only in central donor cornea but also in the recipient peripheral cornea compared with that in the uneventful transplanted corneas. Additionally, the recipient endothelium had significant pleomorphism in the rejection group. There were no morphologic differences in the peripheral donor cornea between the control group and the rejection group. CONCLUSIONS: Our findings indicate that the recipient peripheral endothelium is also affected by allograft rejection, perhaps because of the contribution of recipient endothelium to the wound healing process after allograft rejection.     

Outcome of Corneal transplantation rejection

PURPOSE: To identify predictive factors for reversibility of corneal graft rejection. METHODS: The study design was a prospective cohort study. Among 440 consecutive penetrating keratoplasties performed at our institution, 79 grafts from 79 patients who developed signs of transplant rejection were included. Donor, recipient, surgical, and rejection variables were studied, at both univariate and multivariate levels. RESULTS: The rate of reversibility was 51% (40/79). The average postoperative time of rejection was 10.5 +/- 9.3 months, and the average time of visual acuity recovery in patients with reversible rejection was 2.4 +/- 2.3 months. In logistic regression, only two variables significantly influenced the rate of reversibility. The preoperative diagnosis (p = 0.04) influenced the rate of rejection reversibility; patients with bullous keratopathy or regraft were more likely to experience irreversible rejection than patients with keratoconus or Fuchs' dystrophy. The average graft thickness at the time of rejection diagnosis was 774 +/- 129 microm in patients with irreversible rejection and 681 +/- 118 microm in patients with reversible rejection (p = 0.001). CONCLUSION: Rejection was reversible in half of the cases. Rejection was more likely to be irreversible in patients with marked increase in graft thickness and in patients transplanted for bullous keratopathy or graft failure. Donor variables did not influence rejection reversibility.     

Traumatic wound rupture after penetrating keratoplasty in Africa

AIM: To investigate risk factors, visual outcome, and graft survival for traumatic wound rupture after penetrating keratoplasty. METHODS: A retrospective analysis of 336 patients who underwent penetrating keratoplasty from 1988 to 1995. RESULTS: 19 patients (5.7%) suffered traumatic postoperative wound rupture requiring surgical repair. They were younger (mean age 16.6 years, 95% CI 13.2-20.6) and more frequently keratoconic (p = 0.01) than other patients (mean age 28.9 years, 95% CI 26.-31.0). Mean postoperative follow up was 37.7 (SD 22.9) months and 24.5 (18.9) months for the rupture and non-rupture patients. Mean interval between keratoplasty and rupture was 18 (21) weeks. The lens was damaged and removed in 37% of ruptured eyes. For keratoconics, the probability of graft survival at 5 years was lower (p = 0.03) in the ruptured eyes (75%) than in the non-ruptured eyes (90%). Endothelial failure was a more common (p <0.05) cause of graft opacification in ruptured grafts than in intact grafts. Of the ruptured eyes, 53% achieved a final corrected acuity of at least 6/18 and 63% achieved at least 6/60 compared with 48% and 71% of the intact eyes respectively (both p >0.1). The proportion of keratoconic eyes which achieved at least 6/60 was lower (p = 0.02) in the ruptured eyes (67%) than the non-ruptured eyes (87%). Eyes with wound ruptures of 5 clock hours or greater were less likely (p <0.05) to achieve an acuity of 6/18 and were more likely (p <0.05) to have an associated lens injury. CONCLUSIONS: Graft rupture is relatively common in African practice, particularly in young keratoconics. Visual outcome and graft survival are not significantly worse than for other grafted eyes, but are significantly worse than for other grafted keratoconic eyes.     

INTERRUPTED 10/0 NYLON SUTURES IN PENETRATING KERATOPLASTY

Slow insecure wound healing is a feature of continuous 10/0 monofilament nylon sutures in penetrating corneal grafts. Interrupted sutures of the same type promote more rapid healing but more corneal vascularization occurs; however, if interrupted 10/0 monofilament nylon sutures are removed before blood vessels enter the graft then steroid eye drops can be stopped sooner. No graft displacement or rejection occurred when interrupted monofilament nylon sutures were used in 9 eyes exhibiting a variety of severe corneal diseases.     

Corneal allograft rejection following immunization

Five patients developed corneal allograft rejection after immunization. One patient, a 33-year-old woman, received a tetanus toxoid booster nine months after a corneal transplant for keratoconus. Within four days she developed a graft rejection that required a penetrating keratoplasty two years later. Six months later, after hepatitis B immunization, the patient reported decreased vision and the graft was cloudy, but visual acuity was 20/20. The other four patients developed graft rejection after influenza immunization. Two of these four graft rejection episodes were successfully treated with high-dose corticosteroid therapy; all episodes occurred within several weeks of influenza immunization. Patients should be prudently counseled regarding the possible risks of immunization to corneal allograft survival.     

Corneal transplant allograft reactions in unilateral, double corneal transplants

In support of the idea that the HLA system plays a major role in corneal graft rejection, we report these two unique cases. Both had two penetrating grafts in the same eye. One was a regular graft and the second a patch graft to repair a perforation in the initial one. In the first case, the original graft had an allograft reaction and the patch graft remained unaffected. In the second case, an allograft reaction to the patch graft developed while the regular graft remained completely clear. Both grafts in the two cases cleared following medical therapy. The fact that in these two cases rejection reactions involved one transplant only, even though the other graft was subject to the same conditions, implies that the difference in the antigenicity of the two grafts is an important factor in the chain of events leading to rejection.     

The role of cytotoxic T lymphocytes in corneal allograft rejection

PURPOSE: Immunologic rejection constitutes a major barrier to the success of allogeneic corneal transplants, but the specific mediators and mechanisms of graft rejection are poorly understood. Several studies have implicated cytotoxic T-lymphocyte (CTL) responses, typically associated with CD8(+) T cells, in promoting corneal graft rejection. This study sought to test the hypothesis that CTLs are essential in promoting corneal graft rejection. METHODS: BALB/c donor corneas were grafted orthotopically onto C57BL/6, perforin knockout, or CD8(+) T-cell knockout mice. The tempo and incidence of graft rejection were observed for each group. In separate experiments, donor-specific CTL and delayed-type hypersensitivity (DTH) responses were tested at the time of graft rejection by a standard chromium release assay and an ear swelling assay, respectively. RESULTS: Perforin knockout and CD8(+) T-cell knockout mice were as effective as wild-type C57BL/6 control mice in rejecting BALB/c donor corneas. Furthermore, animals in all three groups were found to develop robust donor-specific DTH, not CTL, responses at the time of graft rejection. Histopathologically, the rejected corneas from all three groups contained a predominantly mononuclear cellular infiltrate. CONCLUSIONS: This study rejects the hypothesis that CD8(+) CTLs are essential in promoting corneal graft rejection and instead further implicates donor-specific DTH reactions as the relevant immune response during graft failure.     

暴露后弹力层的前部深板层角膜移植手术进展

前部深板层角膜移植术（deep anterior lamellar keratoplasty,DALK）是一种新的角膜移植技术,该技术将去除后弹力层和内皮层的供体角膜移植到去除全部基质的植床上,以期望获得与穿透角膜移植术相同的光学效果,同时减少术中和术后并发症.DALK对手术技术要求高,关键步骤是暴露后弹力层.暴露后弹力层的方法经历了直接分离法、基质无菌空气辅助分离法、水分离法、黏弹剂法、大泡技术等,这些技术在不断改进且日趋成熟.DALK的优点是保留了眼球结构和免疫的相对完整性,可减少术后内皮型免疫排斥反应、角膜植片慢性功能失代偿以及角膜植片因外伤哆开的风险.本文就DALK的适应证、手术技术和并发症等进行综述,为其技术改进和广泛临床应用提供思路.     

Tacrolimus (FK506) in the management of high-risk corneal and limbal grafts

OBJECTIVE: To assess the efficacy and side effects of tacrolimus in the management of patients with high-risk corneal and limbal grafts. DESIGN: Noncomparative case series. PARTICIPANTS: Seventeen patients (23 grafts) were treated with tacrolimus; 15 patients (20 host corneas) had two or more quadrants of stromal vascularization, 6 patients had stem cell deficiency, and 6 patients had glaucoma. Seven patients had received one previous graft, six patients had two previous grafts, and four patients had three previous grafts. INTERVENTION: Patients with high-risk corneal and limbal grafts were treated with systemic tacrolimus at a mean optimum dosage of 4.4 mg daily (range, 2-12 mg daily). MAIN OUTCOME MEASURES: Graft survival, visual acuity. RESULTS: No patient has had irreversible graft rejection while receiving tacrolimus. The follow-up period ranges from 12 to 46 months, with a mean of 24 months. Three patients have had reversible graft rejection associated with low tacrolimus levels. Nine patients have stopped treatment; two had reversible rejection within 2 months of stopping, and five grafts remain clear. The other four patients stopped treatment because of graft failure, which was not considered to be rejection related. Eight patients remain on treatment, and all have clear grafts. CONCLUSIONS: Tacrolimus (FK506) is effective in prevention of rejection in patients with high-risk corneal and limbal grafts.