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ARTICLE
Effect of Donor Cornea on the Surgical Outcomes of Penetrating Keratoplasty: Imported Cornea Versus Domestic Cornea

Objectives: In this study, we compared the surgical outcomes of penetrating keratoplasty using domestic and imported donor corneas.

Materials and Methods: We retrospectively evaluated 200 eyes and 200 consecutive patients who underwent penetrating keratoplasty by using domestic and imported donor corneas between January 2013 and December 2013. The donor characteristics, preop­erative clinical features, and clinical outcomes at 6, 12, 24, and 36 months were assessed.

Results: No significant differences existed between the 2 groups with respect to age, sex, lateralization, and penetrating keratoplasty indication (P > .05). Donor age was lower (P = .012), the death-to-preservation time and the preservation-to-surgery time were shorter, the rate of epithelial defect was lower, and the endothelial cell count was higher in the domestic group (P < .001). The 2 groups were also similar in terms of developing persistent epithelial defect, glaucoma, keratitis, and graft survival (P > .05).

Conclusions: We observed no significant differences in clinical outcomes during and after penetrating keratoplasty surgery between imported and domestic donor corneas.


Key words : Corneal transplant, Endothelial cell loss, Eye bank, Graft survival

Introduction

Penetrating keratoplasty (PK) is the tissue transplant procedure with the highest success rate.1 The surgical success of PK is positively correlated with graft survival, which is affected by many preoperative, intraoperative, and postoperative factors. Although the first and the foremost step for achieving graft transparency is transplanting a donor cornea with a sufficient endothelial cell count2-5 and maintaining a sufficient endothelial cell count despite aging, surgical operation and all potential complications are important considerations in the long term.2

As with all other countries, donor tissue supply is an important problem in our country (Turkey). Little endothelial cell loss occurs during donor cornea storage in a solution containing 4°C chondroitin sulfate for up to 14 days, allowing international donor cornea sharing to come into effect.6 Although eye banks have certain standards, some prejudices exist toward donor cornea age, death-to-preservation time, preservation-to-surgery time, transport means, and the effects of these factors on endothelial cell count and corneal epithelium.

Several studies have already investigated endothelial cell lifespan and graft survival with imported corneas.2,7,8 The aim of this study was to compare the 3-year surgical outcomes of PK using imported and domestic donor corneas.

Materials and Methods

This study was approved by the ethics committee of Ankara Training and Research Hospital (Ankara, Turkey), and it conforms to the principles of the Declaration of Helsinki (2008) (study approval number: 192). The medical records of 326 patients who underwent PK at our clinic between January 2013 and December 2013 were retrospectively screened; patients who underwent lamellar or bilateral keratoplasty and patients with limbal stem cell deficiency were excluded. All patients were informed about the surgical procedure and possible complications, and all signed the voluntary informed consent form before treatment. Due to the large number of patients waiting for corneal transplant and the legal requirements in our country, an imported or domestic donor cornea was used regardless of patient risk situation.

Patients enrolled in the study (N = 200) were divided into 2 groups on the basis of donor tissue supply. The domestic group consisted of those who underwent PK with domestic donor corneas (100 eyes in 100 patients), and the imported group included those who underwent PK with imported donor corneas (100 eyes in 100 patients).

Preparation of domestic donor cornea
All domestic donor tissues were obtained from the International Eye Bank of Ankara Training and Research Hospital and were retrieved within 6 hours of death and stored in Eusol-C (Alchimia, Ponte San Nicolò, Italy).

Preparation of imported donor cornea
All imported donor corneas were obtained from the Tissue Bank International (Baltimore, MD, USA). Endothelial cell count, donor age, death-to-preservation time, systemic illnesses of donors, previous surgeries, and cause of death were recorded on specific forms for all donor corneas. All corneas were stored in Optisol-GS (Bausch & Lomb, Bridgewater, NJ, USA) and kept at 4°C in a refrigerated container during 22.5 hour air transport from Baltimore to Turkey every Monday. The corneas were approved after the eye bank director examined them under biomicroscope and counted their endothelial cells (Eye Bank Kerato Analyzer EKA-10, Konan, Hyogo, Japan). Donor corneas with an endothelial cell count of 2000 or more were accepted.

All corneas were stored at 4°C in a refrigerator in the eye bank and transferred to a refrigerator at the operating room on the day of surgery. They were used after being thawed to room temperature at approximately 1 hour before the surgery.

Penetrating keratoplasty
The standard microsurgery technique was used in all patients who underwent PK. Donor corneas that were 0.25 to 0.50 mm larger than the recipient bed were resected from the endothelial surface with a punch trepan. The recipient bed was prepared with a vacuum trepan. After placement of 4 cardinal sutures with 10-0 nylon, the graft was sutured with interrupted or continuous sutures or a combination of these, and the knots were embedded into the recipient cornea. We used 1% sodium hyaluronate as a viscoelastic device. At the end of the operation, the anterior chamber was formed by balanced salt solution, and subconjunctival gentamycin (40 mg/0.5 mL) and dexamethasone (4 mg/1 mL) were injected.

Postsurgical treatment
During the postsurgical period, topical 1% prednisolone acetate (Predforte, Allergan, Irvine, CA, USA) was administered 8 times per day, with tapering over 6 to 12 months. Topical 0.5% moxifloxacin (Vigamox, Alcon, Fort Worth, TX, USA) at 6 times per day was administered for the first 2 weeks, and acetazolamide at 3 × 125 mg/day (Diazomid, Sanofi Aventis, Lüleburgaz, Turkey) was administered for the first 3 days. Systemic corticosteroids, topical lubricants, topical antiglaucomatous agents, and topical/systemic cyclosporine A were added to the regimen as necessary. Medication doses were adjusted by the patient's clinical condition.

Follow-up
All patients were regularly monitored at cornea section on day 1 and during week 1 and then every week for the first 2 months; at 3, 6, 9, 12, 18, and 24 months; and then at each year. At each visit, the best corrected visual acuity was checked, intraocular pressure was measured, and anterior and posterior segment examinations were done.

Clinical outcomes were compared in terms of corneal clarity and development of postoperative complications, including persistent epithelial defect, glaucoma, infection, and immunologic rejection. The clinical outcome was assessed by the demographic characteristics of the patients, donor age, time between donor death and preservation and between preservation and surgery, and the number of endothelial cells in the donor cornea.

Statistical analyses
The Statistical Package for the Social Sciences 16.0 (SPSS Inc. Chicago, IL, USA) software program was used, with statistic analyses done with the use of frequency tables, descriptive tables, Pearson chi-square test, t tests, and one-way analysis of variance. P < .05 was accepted as statistically significant. Phi and Cramer V factors were used for correlation analyses.

Results

Demographic properties of patients and indications for penetrating keratoplasty
Our study included 200 eyes and 200 patients who underwent PK with imported or domestic donor corneas. Demographic properties and indications for PK are presented in Table 1. No significant differences were observed between the groups with respect to age (P = .091), sex (P = .569), laterality (P = .671), and indication for PK (P = .553).

Features of the donor
The preoperative donor features are shown in Table 2. The domestic group had a lower donor age (P = .012), shorter donor death-to-preservation time and preservation-to-surgery time (P < .001), lower rate of donor epithelial defects (P < .001), and higher endothelial cell count (P < .001). The preoperative sizes of donor epithelial defects for both groups are shown in Table 3.

Clinical outcomes
Postoperative clinical outcomes are shown in Table 4. Epithelial integrity was achieved at postoperative week 3 in all cases. At postoperative week 1, epithelial integrity was significantly higher in the domestic group (84/100) than in the imported group (72/100) (P = .041). The 2 groups did not show any significant difference with respect to development of persistent epithelial defects at 6 (P = 1.0), 12 (P = .56), 24 (P = 56), and 36 months (P = .56).

The epithelial defect on corneal graft at postoperative week 1 was significantly correlated to the presence of donor epithelial defect preoperatively (P = .002) and not significantly correlated with the size of donor epithelial defect (P = .163). A significant correlation was found between the presence and size of donor epithelial defect preoperatively and development of persistent epithelial defect on corneal graft during follow-up (P = .018 and P < .001).

Although 5 of 6 patients developed persistent epithelial defects in the domestic group and 1 of 9 patients in the imported group responded to medical treatment, other patients received amniotic membrane transplant in addition to medical treatment.

The 2 groups did not show any significant differences with respect to development of glaucoma at 6 (P = .62), 12 (P = 56), 24 (P = 56), and 36 months (P = 1.0). Although 9 of 12 patients who developed glaucoma in the domestic group responded to medical treatment, 2 patients underwent Ahmed glaucoma valve implantation and 1 received a trabeculectomy. Although 6 of 14 patients in the imported group responded to medical treatment, 6 patients underwent trabeculectomy and 2 underwent Ahmed glaucoma valve implantation.

In the domestic group, 5 herpetic incidences (3 recurrent and 2 newly acquired at 6-12 mo) and 1 bacterial incidence (≤ 6 mo) of keratitis were observed. In the imported group, 5 herpetic incidences (3 newly acquired and 2 recurrent at 6-12 mo), 2 bacterial incidences (12-24 mo), and 1 fungal incidence (6-12 mo) were observed. In addition, Pseudomonas aeruginosa endophthalmitis developed in 1 patient 2 years after surgery.

No significant differences were found between the 2 groups in terms of development of keratitis (P = .788) at the last visit. A significant correlation existed between the presence (P = .022) and size (P < .001) of donor epithelial defect on donor cornea preoperatively and development of keratitis on corneal graft.

The domestic group had significantly higher endothelial cell counts at all time points (P < .001, Figure 1).

No significant differences were found between the 2 groups in terms of graft transparency at 6 (P = .65), 12 (P = .83), 24 (P = .25), and 36 months (P = .23). Eleven cases of graft rejection occurred (6 irreversible) in the domestic group. The imported group had 16 cases of graft rejection (8 irreversible). No significant differences were shown regarding graft survival versus patient age, PK indication, donor age, donor death-to-preservation and preservation-to-surgery times, and endothelial cell count (P > .05).

Correlation analyses revealed that, in the domestic group, the presence of donor epithelial defect was significantly correlated with persistent epithelial defect (P = .02, Phi = 0.23), keratitis (P = .02, Phi = 0.23), epithelial defect at week 1 (P = .002, Phi = 0.31), and rejection reaction (P = .019, Phi = 0.23); however, size of donor epithelial defect was significantly correlated with persistent epithelial defect (P < .001, Cramer V = 0.46) and keratitis (P < .001, Cramer V = 0.55), epithelial defect at week 1 (P = .004, Cramer V = 0.36), and rejection reaction (P < .001, Cramer V = 0.24) . In the imported group, on the other hand, the presence of donor epithelial defect was not correlated with any of the parameters, and the size of donor epithelial defect was correlated with persistent epithelial defect (P < .001, Cramer V = 0.24) and keratitis (P = .01, Cramer V = 0.22).

Discussion

One of the most important problems with keratoplasty surgery is an inadequate supply of donor corneas. This causes long wait times for keratoplasty surgery, leading to socioeconomic and psychologic problems. To overcome this problem, international tissue/cornea sharing has been implemented.

Donor age
To date, many studies have investigated the effects of donor age on graft survival, albeit with inconsistent results.2,3,9-13 Wagoner and associates,2 in a study with imported corneas, reported that, as donor age increased, the risk of endothelial failure increased and graft survival decreased. Despite imported corneas retrieved from significantly older donors, we did not find a relationship between donor age and graft survival, as the success rates for both groups were similar, supporting the findings of Ababneh and associates.3

Time between donor death and surgery
Although imported corneas have mitigated shortages in corneas for transplant, new concerns have been raised about the safety and effectiveness of cornea transplant using imported corneas due to the consideration that transport times may deeply affect infection occurrence and endothelial cell count.2,7,8 The absence of transport time shortens the death-to-surgery time for domestic corneas. Yamazoe and associates8 reported that the mean endothelial cell loss in imported and precut corneas for Descemet stripping automated endothelial keratoplasty surgery was 3.79% by overseas transport, which was acceptable. Hu and associates14 reported that the rate of endothelial cell loss was 23.4% with cornea transport, and they stated that a death-to-surgery time of 7 days or longer was correlated to an increased rate of donor graft failure with imported corneas. It was suggested that preservation-to-surgery times of more than 7 days may be associated with decreased survival of major histocompatibility class II positive dendritic cells,2,15 which may result in a compensatory mechanism of decreased endothelial rejection episodes that offset the loss of endothelial viability associated with prolonged storage.2,16 Doganay and associates17 reported that there was no difference between graft survival after PK using imported corneas with a preservation-to-surgery time of 8 days or longer and domestic corneas with a preservation-to-surgery time of 30 hours or shorter. Wagoner and associates2 reported that the preservation-to-surgery time was the factor that least affected graft survival. In agreement with Shimazaki and associates,7 our study provided evidence that significantly shorter death-to-preservation and preservation-to-surgery times with domestic corneas were not coupled with better graft survival.

Epithelial integrity
Another important parameter affecting graft survival with the use of imported corneas is donor epithelial defects occurring during the preservation-to-surgery time and transport. Whereas some studies have reported a positive correlation between prolonged storage time and postoperative epithelial defects,2,14 others have opposed an association between prolonged storage time and reepithelization and graft survival.17,18 Our study demonstrated a significantly lower rate of epithelial defects with domestic corneas than with the imported ones. It has been reported that the epithelial status at postoperative day 1 did not affect ocular surface status at the first month after PK and graft survival.18 In our study, epithelial integrity was achieved in 3 weeks in all cases, and a significant correlation was seen between donor epithelial defect preoperatively and presence of epithelial defects on corneal graft at postoperative week 1. Although there were no statistical differences between the 2 groups in persistent epithelial defect development in later periods, we observed that the imported group was more resistant and less responsive to medical treatment alone. Hu and associates14 reported that "the use of donor cornea over 7 days between death and surgery affected surgical success with the cause of poor reepithelization and upon arrival, the imported donor corneas had unhealthy corneal epithelium with large epithelial defects and diminished endothelial specular reflection with blurred intercellular borders on specular microscopic examination after long-term storage and overseas transportation."

We also determined a significant correlation between the presence and size of donor epithelial defects preoperatively and graft survival, especially the presence of donor epithelial defects in the domestic group and the size of donor epithelial defect in the imported group preoperatively, which were significantly correlated with development of complications.

Keratitis
Our study is in accordance with a previous report7 and did not demonstrate any significant difference between both groups with respect to development of keratitis. Herpes recurrence and newly acquired herpes infection were observed in both groups. Fungal keratitis was observed in the imported group and endophthalmitis in the domestic group. An interesting finding of our study was that there was a significant correlation between the presence and size of donor epithelial defect and development of keratitis in the domestic group, but this correlation was only seen regarding size of donor epithelial defect and development of keratitis in the imported group. These results seemed to be coincidental but may be explained by the development of more epithelial defects in imported corneas than in domestic corneas due to agitation during transport.

Graft survival
Wagoner and associates2 reported a graft survival rate of approximately 86% at 3 years after PK using imported corneas. Our total graft survival was 86.5% at 3 years (89% for the domestic group and 84% for the imported group). Although graft survival rate was higher in the domestic group, this difference was insufficient to produce statistical significance. Endothelial cell count represents the first and foremost parameter affecting graft survival in the early postoperative period, whereas preservation of endothelial cells is the most important factor in the long term.2 Shimazaki and associates7 reported that, although domestic corneas had a significantly greater endothelial cell count, this difference did not produce any benefit for graft survival. Our study indicated that, although domestic corneas had a significantly greater endothelial cell count preoperatively and postoperatively, this difference did not influence graft survival.

Conclusions

Our results showed that imported donor corneas are as safe and efficacious as domestic corneas, although the imported donors were older, had a longer death-to-surgery time, and a greater rate of epithelial defects. An international cornea sharing system seems to be a reliable alternative for countries having difficulties with donor tissue supplies.


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DOI : 10.6002/ect.2018.0056


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From the 1Department of Ophthalmology, Ankara Training and Research Hospital, Ankara, Turkey; and the 2Department of Ophthalmology, A?r? State Hospital, A?r?, Turkey
Acknowledgements: The authors have not received specific grants from any funding agency in the public, commercial, or not-for-public sectors. The authors declare that they have no conflicts of interest.
Corresponding author: Evin Singar Ozdemir, Ankara Training and Research Hospital, Department of Ophthalmology, Sukriye Mahallesi, Ulucanlar Caddesi, No. 89 Alt?ndag, 06340 Ankara, Turkey
Phone: +90 312 595 34 90 E-mail: evinsingar@yahoo.com