Purpose
To identify patient characteristics influencing treatment outcomes of allograft corneal rejection.
Design
Retrospective case file review.
Methods
Files containing details of first episode of corneal allograft rejections in patients who underwent penetrating keratoplasty at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia from 1991 to 2006 were reviewed. Cases were divided into 2 groups based on the response to treatment for graft rejection: treatment responders and failures. Main parameters evaluated were demographic characteristics, preoperative clinical profile, donor characteristics, surgical technique, presentation, and treatment of rejection episode.
Results
A total of 235 cases of graft rejection were identified, of which 195 cases (83%) were successfully treated and 40 (17%) failed to respond. Age ( P = .08) and gender ( P = .61) were comparable in both groups. On univariate analysis, primary diagnosis of keratoconus ( P = .04) and phakic lens status at the time of surgery ( P = .02) were more common in treatment responders whereas aphakic bullous keratopathy ( P ≤ .01), history of glaucoma ( P < .01), aphakia ( P < .01), and previous grafts ( P < .01) were more common among treatment failures. Multivariate analysis revealed that preoperative corneal neovascularization (adjusted odds ratio [aOR] 3.6, 95% CI: 1.3-9.7, P = .01), a larger (>9 mm) donor size (aOR 5.7, 95% CI: 1.3-24.9, P = .02), and corneal edema at presentation (aOR 4.7, 95% CI: 1.7-13.2, P < .01), were independently associated with failure of treatment of graft rejection.
Conclusions
Treatment failure in cases of corneal allograft rejection is more likely to occur among patients with corneal neovascularization, large donor graft buttons, and corneal edema at presentation.
Corneal diseases are a significant cause of global blindness. When managing patients with severe corneal pathologies, corneal transplantation, which was first performed in 1905, remains one of the most important surgical techniques for restoring vision. The first-year survival rates after corneal transplantation surgery are estimated to be 88%. However, the survival rate steadily falls to about 55% at 5 years, mostly because of allograft corneal rejection. Although the eye is an immunologically privileged site, graft rejection accounts for about one-third of all failures in corneal grafting. Risk factors such as corneal neovascularization and herpetic keratitis, where the eye’s innate immunologic privilege is compromised, have been demonstrated in large multicenter trials to predispose to such an episode of rejection. When a patient presents with an episode of graft rejection, it is important for the clinician to know the likelihood of the rejection episode proceeding to failure, and as such, an appropriate modality of treatment can be chosen. The present study is an endeavor to identify and analyze patient characteristics and clinical features at the time of presentation of a graft rejection episode that are likely to signify an increased risk of graft failure, thus allowing the treating ophthalmologist to tailor treatment more accurately to the circumstances.
Methods
A retrospective case file review was performed of all first-episode corneal graft rejections occurring between 1991 and 2006 at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. Patients were divided into 2 categories: “treatment responders” (successfully treated episode of corneal graft rejection) and “treatment failures” (failed treatment of corneal graft rejection). Patients who were less than 18 years old at the time of corneal grafting and patients who did not undergo a full-thickness keratoplasty were excluded from this study.
Graft rejection was defined as any episode involving the following features: 1) edema in a previously clear graft, 2) presence of keratic precipitates (KP), 3) presence of an epithelial or endothelial rejection line, or 4) presence of cells and flare in the anterior chamber (AC). Treatment of a graft rejection episode was considered successful if there was a decrease in steroid medication, combined with decline in corneal edema, AC activity, and epithelial or endothelial lines, for 2 or more consecutive follow-up appointments. The graft rejection treatment was considered to have failed in the absence of fulfillment of these treatment criteria.
Demographics, preoperative clinical profile, donor tissue details, surgical details of penetrating keratoplasty (PK), details of rejection episode, treatment, and outcome of rejection episode information were all meticulously recorded from patient files.
Statistical Analyses
Univariate analyses using χ 2 statistic for categorical and Mann-Whitney U or 1-way analysis of variance for continuous data were performed to identify factors that differed between treatment responders and treatment failures. A P value of <.05 was used to indicate statistical significance. Binary logistic regression analyses were performed for variables that were statistically significant in the univariate analyses. Data were analyzed using the SPSS statistical software (Version 16, SPSS Science, Chicago, Illinois, USA).
Results
A total of 880 cases of PK performed between 1991 and 2006 were identified. Of these, 235 cases of corneal graft rejection met our inclusion criteria and were included in the final analysis. Cases were enrolled based on the documentation of a combination of any of the characteristic signs of graft rejection in the records. These cases were divided into 2 groups: treatment responders (n = 195, 83%) and treatment failures (n = 40, 17%).
Preoperative Clinical Characteristics
Age (P = .08) and gender (P = .61) were comparable in both groups ( Table 1 ). Keratoconus was more common as the primary indication for surgery in treatment responders (P = .04), whereas the treatment failure group had more patients with aphakic bullous keratopathy (ABK) (P ≤ .01). A history of glaucoma (P < .01) and previous grafts in the ipsilateral eye was more common among treatment failures (P < .01). Corneal neovascularization was significantly more common among treatment failures (P < .01). Lens status among eyes was different between the 2 groups. Among treatment responders, 56% of patients were phakic and only 6% were aphakic, which was significantly different (P = .02 and P < .01) from treatment failures. Other variables studied in this category did not show any significant difference between the 2 groups ( Table 1 ).
| All (n=235) | Treatment Responders (n=195) | Treatment Failures (n=40) | P Value | |
|---|---|---|---|---|
| Gender | ||||
| Male | 55% | 57% | 53% | .61 |
| Female | 45% | 43% | 47% | |
| Age (years) | ||||
| (Mean ± SD) | 60 ± 19 | 60 ± 19 | 64 ± 22 | .08 |
| Indication for graft | ||||
| PBK | 32% | 30% | 38% | .46 |
| Keratoconus | 19% | 21% | 8% | .04 |
| Corneal ydstrophy | 17% | 19% | 13% | .49 |
| Herpetic keratitis | 13% | 13% | 12% | 1.0 |
| Postinfectious keratitis scar | 6% | 7% | 5% | 1.0 |
| Post-traumatic scar | 6% | 5% | 7% | .71 |
| ABK | 6% | 4% | 17% | <.01 |
| Other | 1% | 1% | 0% | 1.0 |
| Previous grafts | ||||
| None | 83% | 85% | 73% | <.01 |
| 1 | 10% | 9% | 12% | |
| 2 | 4% | 4% | 5% | |
| 3 or more | 3% | 2% | 10% | |
| Past ocular history | ||||
| Glaucoma | 19% | 15% | 38% | <.01 |
| HSV | 10% | 10% | 10% | 1.0 |
| Diabetes | 8% | 8% | 5% | .75 |
| Prior retinal surgery | 6% | 5% | 13% | .07 |
| Lens status | ||||
| Phakic | 52% | 56% | 35% | .02 |
| Pseudophakic | 38% | 38% | 40% | .86 |
| Aphakic | 10% | 6% | 25% | <.01 |
| Presence of preoperative clinical signs | ||||
| Corneal edema | 64% | 76% | 62% | .07 |
| Corneal neovascularization | ||||
| −0 quadrant | 75% | 81% | 47% | <.01 |
| −1 quadrant | 6% | 6% | 8% | |
| −≥2 quadrants | 19% | 13% | 45% | |
| Intraocular pressure | ||||
| mm Hg (mean ± SD) | 15 ± 5 | 15 ± 5 | 16 ± 5 | .50 |
Donor Graft Characteristics
Donor graft characteristics were similar between both groups when assessed for donor age, gender, preservative used, storage time, and endothelial cell counts. However, a large donor button, >9 mm in diameter, was more commonly used in the treatment failure group (P = .04) ( Table 2 ).
| All (n=235) | Treatment Responders (n=195) | Treatment Failures (n=40) | P Value | |
|---|---|---|---|---|
| Age (years), mean ± SD | 58 ± 21 | 58 ± 20 | 58 ± 27 | .30 |
| Gender | ||||
| Male | 65% | 74% | 64% | .25 |
| Female | 35% | 26% | 36% | |
| Preservative used | ||||
| McCarey-Kaufman | 32% | 30% | 46% | .08 |
| Optisol | 68% | 70% | 54% | |
| Donor graft size (mm) | ||||
| <8 mm | 22% | 24% | 16% | .51 |
| 8-9 mm | 70% | 70% | 67% | .69 |
| >9 mm | 8% | 6% | 17% | .04 |
| Storage time (hours), mean ± SD | 6 ± 4 | 6 ± 4 | 6 ± 4 | .76 |
| Endothelial cell count (cells/mm 2 ), mean ± SD | 2512 ± 355 | 2515 ± 347 | 2497 ± 396 | .74 |
Surgical Technique
When surgical technique employed was compared, we found that there were no significant differences between the 2 groups ( Table 3 ).
| All (n=235) | Treatment Responders (n=195) | Treatment Failures (n=40) | P Value | |
|---|---|---|---|---|
| Suture type | ||||
| Interrupted | 77% | 75% | 87% | .21 |
| Continuous | 17% | 19% | 8% | |
| Mixed | 6% | 6% | 5% | |
| Associated surgery a | ||||
| Cataract surgery | 20% | 20% | 22% | .67 |
| IOL insertion/exchange | 11% | 12% | 5% | .27 |
| Anterior vitrectomy | 10% | 9% | 15% | .26 |
| Complication (resuturing) | 16% | 15% | 23% | .23 |
a Note that each patient may have had 1 operation, multiple concurrent operations, or none.
Presentation of Rejection Episode
Once a patient developed a rejection episode, the clinical details at presentation were recorded, as shown in Table 4 . Presence of corneal edema occurred in 62% of treatment failures, whereas only 30% of treatment responders showed signs of corneal edema (P < .01) ( Table 4 ).
