EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: In this study, we report the indications and outcomes of repeat penetrating keratoplasty and the reasons for graft failure.

Materials and Methods: We performed a retrospective data analysis of patients who had undergone 2 or more penetrating keratoplasties for the same eye between 1991 and 2016.

Results: Among 1613 penetrating keratoplasties, 149 regrafts of 105 eyes were reviewed. The mean follow-up time after repeat penetrating keratoplasty was 3.2 ± 3.9 (range, 3 months to 17 years) years. The mean number of penetrating keratoplasties was 2.25 ± 0.69 per eye (range, 2-6). The most common primary indication for repeat penetrating keratoplasty was bullous keratopathy (31.4%), which was followed by corneal dystrophy (20.0%). The mean follow-up time was 8.05 ± 5.03 years (range, 8 mo to 24.75 y). At the last follow-up, 62 eyes (59%) had clear grafts and the mean best-corrected visual acuity was 1.26±0.99 (range, 0-3) logMAR. Endothelial failure, especially late endothelial failure (36.9%), and glaucoma-related endothelial failure (18.8%) were the most common reasons for failed grafts. Allograft rejection (17.4%) and graft infection (14.1%) constituted the next most frequent causes.

Conclusions: Graft failure is a common indication among penetrating keratoplasties. Primary indications and reasons for failed grafts affect long-term outcomes. Therefore, a better understanding of the indications for risk, leading causes of failed grafts, and complications could help to determine effective preventive measures.

Key words : Graft failure, Penetrating keratoplasty, Repeat penetrating keratoplasty

Despite the increasing success of penetrating keratoplasty (PK) due to advances in surgical techniques and ocular therapies, graft failure still remains an important problem.^1-3 The risk for a failed graft is closely associated with the primary PK indication.⁴ Repeat PK, which has become an increasing indication after a first PK, has a greater risk of graft failure.⁵ Hence, it is important to understand the indications and outcomes of repeat PKs.

Our department maintains a large corneal transplant database that includes our records of more than 20 years. Here, we retrospectively analyzed the indications and outcomes of repeat PKs at our center and compared our findings with results across the literature.

Materials and Methods

We performed a retrospective data analysis of patients who had undergone repeat PK between 1991 and 2016 at our center. Patient records were reviewed for age, sex, primary PK indication, total number of transplanted grafts (PKs), follow-up time, reasons for graft failure, graft clarity, final postoperative best-corrected visual acuity (BCVA) (as measured with Snellen chart), and conditions leading to reduction in vision in clear grafts.

Primary indications for the first PK were categorized as follows: bullous keratopathy (BK) (aphakic or pseudophakic), corneal dystrophy, keratoconus, herpetic keratitis, fungal keratitis, trauma, nonspecific vascularized scar, chemical injury, descemetocele (± perforation), congenital glaucoma, and keratoglobus. Allograft rejection, endothelial failure with no evidence of allograft rejection (either primary or late), recurrence of previous disease (either herpetic recurrence or recurrence of dystrophy), uncontrolled secondary glaucoma leading to corneal endothelial failure, graft infection, trauma, and ocular surface pathology composed the main reasons for failed grafts. “Allograft rejection” was defined as the presence of one or both endothelial and/or epithelial rejection, corneal edema, and keratic precipitates. “Graft failure” was defined as the presence of an irreversible graft edema. Graft clarity loss detected within 2 weeks after surgery was defined as “primary graft failure,” and graft clarity loss detected 2 weeks after surgery was termed as “late endothelial failure.” Intraocular pressure elevation (≥21 mmHg) on 2 separate examinations was defined as “secondary glaucoma.”Corneal grafts were categorized according to clarity as clear, transparent, or opaque.

We also classified eyes that underwent repeat PK into groups: those with 2 PKs per eye (group 1) and those with more than 2 PKs per eye (group 2).

Statistical analyses were performed using SPSS software for Windows version 15.0 (SPSS Inc, Chicago, IL, USA) and Microsoft Office Excel (Microsoft, Redmond, WA, USA). Statistical analyses were performed by frequency tables and chi-square test. P < .05 was accepted as statistically significant.

The incidence of repeat PK was 9.23% among 1613 PKs. The male-to-female ratio was 70:34 with a mean age of 58.94 ± 19.24 years (range 4-85 y) at the time of repeat PK. The overall mean follow-up time was 8.05 ± 5.03 years (range, 8 mo to 24.75 y). The mean follow-up time after the second PK was 3.2 ± 3.9 years (range, 3 mo to 17 y). The total PK number was 236, with a mean of 2.25 ± 0.69 per eye (range, 2-6).

The most common indication for primary PK was BK with a rate of 30.3% (4 aphakic and 29 pseudophakic). The other indications included corneal dystrophy (20.2%), herpetic keratitis (8.9%), nonspecific vascularized scar (7.9%), keratoconus (5.6%), descemetocele (± perforation) (5.6%), fungal keratitis (4.5%), trauma (4.5%), chemical injury (3.4%), congenital glaucoma (3.4%), and keratoglobus (1.1%) (Table 1). Eighty-nine eyes (84.8%) underwent 2 PKs, 10 eyes (9.5%) had 3 PKs, 3 eyes (2.8%) had 4 PKs, 2 eyes (1.9%) had 5 PKs, and 1 eye (0.9%) had 6 PKs.

The most common reason for primary graft failure was late endothelial failure (36.9%), which was followed by glaucoma-related endothelial failure (18.8%) and allograft rejection (17.4%). Table 2 details the conditions leading to graft failure. The interval between primary PK and the first graft failure ranged from 7 days to 16.9 years, with a mean of 5.8 years. At the last visit, 62 grafts (59%) were clear, 21 (20%) were transparent, and 27 (25.7%) were opaque (Table 3). Among patients with 2 graft failures, repeat PKs were not recommended for 7 patients, due to advanced glaucoma in 4 patients, post-PK endophthalmitis due to fungal infection in 1 patient, maculopathy in 1 patient, and history of vitreoretinal surgery in 1 patient. In addition, 7 patients are still on the cornea wait list for a repeat PK. Three eyes showed phthisis bulbi and 2 eyes underwent evisceration surgery after the second PK (with 1 patient having a painful glaucomatous eye unresponsive to medical intervention and 1 patient requiring prevention of spread of fungal infection in eye). Among those 5 patients who showed phthisis bulbi or underwent evisceration surgery, 2 (1 phthisis bulbi, 1 evisceration) had BK, 2 (1 phthisis, 1 evisceration) had fungal keratitis, and 1 had keratoconus, primarily. The patient with keratoconus, who ended up with phthisis bulbi, had a penetrating eye trauma complicated with retinal detachment; the patient underwent vitreoretinal surgery during follow-up. Other conditions leading to reduction in BCVA in clear grafts are listed in Table 4. The mean preoperative BCVA was 2.08±0.91 logMAR (range, 0.3-3.10). The mean BCVA of the clear grafts was 1.26±0.99 logMAR (range, 0-3).

In our subgroup analysis (Tables 1 and 3), we found no statistically significant differences regarding primary indications, BCVA, and last graft clarity between group 1 and group 2. Clear grafts at last follow-up showed better BCVA than others. Bullous keratopathy was the most prevalent primary indication for clear and opaque grafts, and corneal dystrophy was the most common indication for transparent grafts at last follow-up (P = .033). The most common reason for graft failure was late endothelial failure for clear and transparent grafts; however, glaucoma-related endothelial failure was the most common reason for graft failure for opaque grafts (P = .037).

Graft failure, which is one of the most undesired consequences in PK, has become an increasing indication for repeat PKs.^1-3 The ratio of repeat PKs has been reported to be 6% to 41% among all keratoplasty surgeries.^3,6-15 In the present study, the percentage of repeat PKs among all PKs was 9.23%, which is consistent with the literature. The primary indication for repeat PKs is a key concern for graft outcomes.

Long-term BK is sometimes accompanied by corneal vascularization, which may lead to allograft rejection and then perhaps to graft failure. Additional surgical interventions may also be required during follow-up for eyes with this condition. These further potentiate the risk of endothelial damage and eventual graft failure.¹⁶In this study, the most common indication of repeat PKs was BK, which is in agreement with the literature.^2,13 In subgroup evaluation, BK was also the most common primary indication for clear and transparent grafts. Although corneal dystrophy seemed to be the most prevalent primary indication for transparent grafts, the number of eyes in the subgroups was relatively low for the comparison to be clinically significant. In addition, total follow-up time is an important determinant of the last graft clarity. The eyes having 2 PKs seemed to have shorter total follow-up time. These grafts were also composed of ones that underwent a recent PK (mean regraft follow-up of 2.32 months, with range of 26 days to 4.82 months). For this reason, long-term outcomes cannot be precisely determined from our data.

The primary reason for graft failure is also as critical as the primary indication for repeat PK. Various reasons for failed grafts have been reported in the literature. Although allograft rejection was the most common reason reported by Vail and associates¹⁷ (34%) and Yalniz-Akkaya and associates¹¹ (40%), Vanathi and colleagues¹⁰ reported that 33.9% of the failed grafts were due to ocular surface problems. Both Patel and colleagues¹ (61%) and Rapuano and colleagues9 (34%) attributed endothelial failure as the most common reason for graft failure. In our study, the most common reason for graft failure was late endothelial failure (35.71%); among all types of endothelial failure (primary, late, or glaucoma related), the percentage was 57% among repeat PKs, which is consistent with results from Patel and associates.¹

We found glaucoma-related endothelial failure to be the most common reason for opaque grafts. This can be explained by the chronic effects of glaucoma on subsequent grafts. In addition, underlying glaucoma may affect a clinician’s decision in recommending repeat PKs. Thus, the incidence of failure of opaque grafts was less due to glaucoma, with eventually PK not performed at the end at all. In this study, allograft rejection rate was 17.44% among failed grafts. This relatively lower rate may be explained by several factors such as optimized frequency of topical corticosteroid medications according to the risk for allograft rejection, the use of topical cyclosporine (Restasis, Allergan, Irvine, CA, USA) to increase the quality of the ocular surface, patient education about the warning signs of graft failure, and the significance of compliance with follow-up visits to our clinic. Graft infection also constituted a significant number of failed grafts. This can be explained by the fact that our clinic is a tertiary referral center in which many devastating keratitis cases, including refractory fungal keratitis, are frequently encountered.

Visual outcome is another important issue with regard to repeat PK. A BCVA of ≥ 0.3 logMAR has been reported to be 4.8% to 41% among regrafts.^1,2,12 In the present study, the rate of BCVA of ≥ 0.3 logMAR was 18.09%, which is also consistent with the literature. Graft survival and visual outcomes have been reported to decrease with each transplant.¹¹ However, we observed no statistically significant differences between group 1 and group 2 in terms of BCVA. This may be due to the presence of grafts either with recent PK or presence of sutures in group 1. Therefore, this comparison does not fully reflect the actual visual outcomes and presumably grafts having 2 PKs would have better BCVA in the long run.

In conclusion, BK is the most prevalent primary indication for repeat PKs, whereas endothelial failure, especially late endothelial failure, is the most common reason for failed grafts. These findings emphasize the importance of preventive measures focused on decreasing both the number of graft failures and repeat PKs.

Volume: 19 Issue: 1 January 2021

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