Methods

All penetrating corneal transplants registered by the United Kingdom (UK) Transplant Registry between April 1999 and March 2006, in recipients aged 17 years or above undergoing their first transplant and for whom follow-ups were completed for at least 1 year, were included. These data are held by the National Health Service Blood and Transplant (NHSBT). As in other reports, patients were classified as having glaucoma at the discretion of their treating ophthalmologist based upon 1 or more features of intraocular pressure elevation, optic disc damage, and visual field changes. A breakdown of this information regarding the type of glaucoma was not available to us. Patients were, however, classified according to whether they had 1) been treated by topical or oral glaucoma medication either prior to or following PK or 2) undergone glaucoma surgery at the time of or following PK. Data on recipient eyes and transplants recorded at registration include indication for PK, previous intraocular surgery, transplant diameter, presence of risk factors for rejection (inflammation and vascularization), medications, and previous rejection episodes, as previously described. Follow-up data routinely collected at 1, 2, and 5 years post-transplant include graft failure date, best-corrected visual acuity (BCVA), glaucoma, and steroid medications.

Statistical analyses were performed using SAS v9.1 software (SAS Institute Inc, Cary, North Carolina, USA). χ ² tests and t tests were used, respectively, to investigate differences in categorical and continuous variables. Kaplan-Meier survival curves were used to determine graft survival and a Cox regression model was fitted to investigate the influence of glaucoma on graft survival while adjusting for other known factors. Visual acuity data were converted into logMAR units for analysis, and refractive data were transformed into Long’s matrix formalism and analyzed by the method of Kaye and Harris. The refractive error data are presented in spherocylinder form with the magnitude of the cylinder, treated as a scalar value, also included in square brackets, that is, sphere/cylinder[cylinder] axis.

Results

There were 8249 first PKs for which follow-up was reported to the UK Transplant Registry, of which there were 1994 eyes with glaucoma (24%). The return rate of completed postoperative data within the first 3 years was 85%. The mean ages at PK surgery were 57 years (SD 22 years) for patients without glaucoma (female-to-male ratio: 49:51) and 65 years (SD 19 years) for patients with glaucoma (female-to-male: 47:53).

Graft Survival

Univariate Kaplan-Meier curves showed that 3-year graft survival was lower for patients with glaucoma compared to patients without glaucoma ( Figure 1 ): 72% (95% confidence interval [CI] 70-74) and 86% (95% CI 85-87) respectively (P < .0001). Graft survival was also lower for patients who underwent glaucoma surgery compared to those whose glaucoma was managed by medical therapy alone ( Figure 2 ): 63% (95% CI 51-72) and 73% (95% CI 70-75) respectively ( P < .0001). For patients who had either combined PK glaucoma surgery (n = 32) or post-PK glaucoma surgery (n = 72), graft survival was 68% (95% CI: 45-83) and 60% (95% CI: 46-72), respectively ( P = .5).

Kaplan-Meier survival of penetrating keratoplasty in patients without glaucoma (solid line, n = 6255) and patients with glaucoma (dotted line, n = 1994).

Kaplan-Meier survival of penetrating keratoplasty in patients whose glaucoma was managed by medical therapy alone (solid line, n = 1890) and patients who underwent glaucoma surgery (dotted line, n = 104).

After adjustment for a number of confounding factors, the risk of graft failure was higher for both patients with glaucoma ( Table 2 ). Graft survival, however, was also dependent on the indication for PK, that is, keratoconus (94%), Fuchs dystrophy (91%), PBK (71%), ABK (70%), infection (72%), injuries (69%), ulceration (61%), unknown opacification (85%), and other (78%) (data not shown). Relative to the risk of graft failure for patients with keratoconus, the risk of graft failure was significantly increased for patients with all other indications ( Table 2 ). In terms of other risks factors, ocular surface inflammation and infection/inflammation carried increased relative risks of graft failure of 1.5 and 1.4 respectively.

TABLE 2

Risk-Adjusted Cox Proportional Hazards Model for Penetrating Keratoplasty Failure at 3 Years by Indication for Graft and Presence of Glaucoma and Glaucoma Medication

Factor	No. of Patients	Relative Risk (95% CI)	P
Indication for graft
Keratoconus	2028	1.0
Fuchs dystrophy	1829	1.5 (1.2-2.0)	.002
Pseudophakic bullous keratopathy	1692	3.9 (3.1-5.0)	<.0001
Aphakic bullous keratopathy	230	3.8 (2.6-5.3)	<.0001
Infection	827	3.3 (2.5-4.3)	<.0001
Trauma	242	4.4 (3.2-6.2)	<.0001
Noninfectious ulceration	257	3.7 (2.6-5.3)	<.0001
Unknown opacification	378	2.2 (1.5-3.1)	<.0001
Other	633	2.8 (2.1-3.7)	<.0001
Preoperative glaucoma
No	7309	1.0
Yes	807	1.5 (1.3-1.8)	<.0001
Postoperative glaucoma medication
None	6471	1.0
Topical	1417	1.2 (1.0-1.4)	.02
Oral with/without topical	228	1.5 (1.2-2.0)	.002

CI = confidence interval; PK = penetrating keratoplasty.

Other factors adjusted for: inflammation/infection, recipient trephine diameter, donor-recipient trephine difference, ocular surface disease, donor sex, PK for only visual reasons, and vitrectomy at time of PK

Graft Survival in Patients With and Without Glaucoma According to Indication for PK

For patients undergoing PK for PBK/ABK there was a significant reduction in graft survival between patients with and without glaucoma (63%, n = 809, 95% CI: 59-67 vs 77%, n = 1138, 95% CI: 73-80, P < .0001). The risk of graft failure was higher if on topical or oral antiglaucoma medication ( Table 3 ). Excluding PBK and ABK, for patients who had previous ocular surgery, although there was a reduction in graft survival, there was no statistically significant difference between those with and without glaucoma (62%, n = 62, 95% CI: 50-73 vs 75%, n = 39, 95% CI: 57-87, P = .2) (data not shown).

TABLE 3

Relative Risk of Penetrating Keratoplasty Failure at 3 Years Related to Use of Antiglaucoma Medication in Patients With Fuchs Dystrophy and Pseudophakic Bullous Keratopathy

Factor	No. of Patients	Relative Risk (95% CI)	P
Fuchs dystrophy
Postoperative glaucoma medication
None	1549	1.0
Topical	255	1.9 (1.2-2.8)	.001
Oral with/without topical	25	3.1 (1.3-7.5	.01
Pseudophakic bullous keratopathy
Postoperative glaucoma medication
None	1131	1.0
Topical	474	1.5 (1.2-1.9)	.0003
Oral with/without topical	87	2.0 (1.4-2.9)	.0002

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