Abstract
Aim
To determine graft survival and visual outcome after repeat penetrating keratoplasty (PKP).
Methods
Retrospective review of the medical records patients who underwent repeat PKP at the King Khaled Eye Specialist Hospital (KKESH) between 1 January 1991 and 31 December 2002.
Results
243 repeat PKP performed in 210 eyes of 208 patients, who had also had initial PKP at KKESH, were included in the study. The mean follow up was 43 months (range 1–170). At the most recent examination, 114 (54.3%) grafts were clear. The overall survival rate was 98% at 1 year, 83% at 2 years, and 49% at 5 years. The best graft survival was in eyes with an original diagnosis of keratoconus (93.8%) and the worst was in eyes with Fuchs' dystrophy (23.1%). Overall, 29.6% of eyes achieved a final visual acuity greater than 20/200, while only 4.8% were 20/40 or better. The best visual prognosis was in eyes with an original diagnosis of stromal dystrophy and keratoconus.
Conclusion
Although the prognosis for repeat PKP is poorer than that of initial PKP, reasonable outcomes can be obtained with repeat PKP with careful case selection.
Keywords: corneal transplantation, graft failure, repeat penetrating keratoplasty
Repeat corneal transplantation continues to be an important and increasingly common indication for penetrating keratoplasty (PKP).1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23 In most large eye care centres, repeat PKP is the second leading indication for corneal transplantation, accounting for a mean of approximately 18% (range, 6% to 41%) of cases performed.1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23 In the United States, repeat PKP increased from 6.9% of cases performed in 1992 to 11.3% of cases performed in 1997. At the King Khaled Eye Specialist Hospital (KKESH) in Saudi Arabia, repeat PKP accounted for only 3.2% of cases of keratoplasty performed between 1988 and 1992, but accounted for 11.3% of cases performed between 1998 and 2002, despite a constant total number of corneal transplants.23
The present study provides insights into the contributions of indications for initial keratoplasty to repeat PKP, and provides valuable prognostic information that will assist ophthalmologists and patients in making the decision as to whether or not to proceed with another attempt after graft failure.
Patients and methods
After obtaining approval from the institutional review board, medical records of every patient who underwent repeat PKP at KKESH between 1 January 1991 and 31 December 2002 were retrospectively reviewed. Patients who had their initial PKP at KKESH were included in the study, while patients who had initial keratoplasty (lamellar or penetrating) elsewhere, but were subsequently referred to KKESH for repeat PKP were excluded from the analysis. Patients who had repeat PKP at KKESH after previous lamellar keratoplasty at KKESH were excluded from the analysis.
All cases were performed by members of the anterior segment division of the department of ophthalmology at KKESH utilising donor tissue that fulfilled all requirements of the Eye Bank Association of America. Topical corticosteroids and antibiotics were administered in tapering dosage after surgery. Topical antibiotics were discontinued after approximately 2 weeks, but topical steroid treatment continued for at least the first 6 months. Most patients were evaluated on the first postoperative day, after 2 weeks, after 3, 6, 9, 12, 18, 24 months, and yearly thereafter. The protocol for suture removal varied between ophthalmologists, with some removing all sutures after 12–36 months, and others only selectively removing loosened sutures or tight sutures that induced unacceptable astigmatism.
Data extracted included the original diagnosis responsible for the decision to perform the first corneal transplant, preoperative risk factors, concomitant operative procedures, postoperative complications, graft clarity, and visual acuity. Graft clarity was recorded at the most recent examination in all eyes, as well as just before additional repeat PKP. Graft failure was strictly defined as irreversible loss of central graft clarity, irrespective of the level of visual acuity. The time of graft failure was defined as the visit at which irreversible loss of graft clarity was first documented. Postoperative visual acuity was recorded at the most recent follow up examination. The best corrected visual acuity was used, if available. If the best corrected visual acuity was not available, uncorrected visual acuity was used for purposes of statistical analysis.
All data were entered onto a Microsoft Excel spreadsheet and analysed using two commercial statistical software packages, SPSS g (1998) and Epi‐Info 6 (1994). The χ2 test, the Fisher exact test, and the t test were used for analysis of variance. Nominal p values were used for all comparisons, and the term significance was accepted if the p value was <0.05. Graft survival curves were produced using the standard Kaplan‐Meier methods and the life table. Data were entered and analysed separately for each eye for patients undergoing bilateral repeat PKP.
Results
A total of 473 repeat PKP were performed at KKESH during the study period. Of these, 243 repeat PKP that were performed in 210 eyes of 208 patients after failure of initial PKP done at KKESH were included in the study. The remaining 230 were done after failure of initial keratoplasty performed elsewhere or following failure of lamellar keratoplasty done at KKESH and were not included in the study. Among included cases, mean patient age at the time of surgery was 60.4 (SD 16.3) years (range 14–100). The mean follow up was 43 months (range 1–170).
The initial indications for corneal transplantation at KKESH in eyes that subsequently underwent single or multiple repeat PKP are summarised in table 1. Ten or more cases were performed for six different initial diagnostic categories. The leading indication for repeat PKP was pseudophakic/aphakic bullous keratopathy (PBK/ABK), followed, in order, by corneal scarring, keratoconus, Fuchs' dystrophy, therapeutic/tectonic PKP, and stromal dystrophy.
Table 1 Initial indication v repeat penetrating keratoplasty.
| Initial indication | Eyes | % (eyes) | Repeat PKP 1 | Repeat PKP 2 | Repeat PKP 3 | Repeat PKP 4 | Total cases | % (total cases) |
|---|---|---|---|---|---|---|---|---|
| PBK/ABK | 62 | 29.5 | 62 | 5 | 2 | 0 | 69 | 28.4 |
| Scar | 53 | 25.2 | 53 | 5 | 3 | 1 | 62 | 25.5 |
| Keratoconus | 16 | 7.6 | 16 | 1 | 0 | 0 | 17 | 7.0 |
| Fuchs' dystrophy | 13 | 6.2 | 13 | 3 | 1 | 0 | 17 | 7.0 |
| Therapeutic/tectonic | 12 | 5.7 | 12 | 1 | 1 | 0 | 14 | 5.8 |
| Stromal dystrophy | 12 | 5.7 | 12 | 0 | 0 | 0 | 12 | 4.9 |
| Others | 42 | 20.0 | 42 | 10 | 0 | 0 | 52 | 21.4 |
| Total | 210 | 100.0 | 210 | 25 | 7 | 1 | 243 | 100.0 |
PBK/ABK, pseudophakic/aphakic bullous keratopathy; PKP, penetrating keratoplasty.
The number of eyes in which repeat PKP was done was 4.2% of the total number of primary PKP done in the same period (table 2). This ratio ranged from a high of 12.3% for eyes with PBK/ABK to a low of 1.2% for eyes with keratoconus. Eyes with PBK/ABK were significantly over‐represented as a relative contributing factor to repeat PKP compared to initial PKP (29.5% v 10.6%, p = 0.001), while those with keratoconus were significantly under‐represented (7.6% v 27.9%, p = 0.001). There was no significant difference in the relative contributions of the indications of corneal scars, Fuchs' dystrophy, therapeutic/tectonic, or stromal dystrophy to initial or repeat keratoplasty.
Table 2 Indications for initial and repeat penetrating keratoplasty (1991–2002).
| Initial indication | Repeat PKP (eyes) | Relative contribution (%) | Initial keratoplasty (eyes) | Relative contribution (%) | p Value* | Repeat PKP/ initial keratoplasty (%) |
|---|---|---|---|---|---|---|
| PBK/ABK† | 62 | 29.5 | 506 | 10.6 | <0.001 | 12.3 |
| Scar | 53 | 25.2 | 1577 | 32.9 | NS | 3.4 |
| Keratoconus | 16 | 7.6 | 1339 | 27.9 | <0.001 | 1.2 |
| Fuchs' dystrophy | 12 | 6.2 | 136 | 2.8 | NS | 9.6 |
| Therapeutic/tectonic | 12 | 5.7 | 397 | 8.3 | NS | 3.0 |
| Stromal dystrophy | 12 | 5.7 | 197 | 4.1 | NS | 6.1 |
| Others | 42 | 20.0 | 644 | 13.4 | 0.02 | 6.5 |
| Total | 210 | 100.0 | 4796 | 100.0 | 4.2 |
*Variation in relative contribution as a cause of initial PKP v relative contribution to repeat PKP.
†PBK/ABK, pseudophakic or aphakic bullous keratopathy; PKP, penetrating keratoplasty.
There was a repeat PKP survival rate of 98% at 1 year, 83% at 2 years, and 49% at 5 years. At the most recent examination, 114 (54.3%) grafts were clear after one or more repeat PKP (table 3), ranging from a high of 93.8% in eyes in which the initial PKP was performed for keratoconus to a low of 23.1% in eyes with an initial diagnosis of Fuchs' dystrophy (table 4). The likelihood of survival of a repeat PKP was significantly correlated with the diagnosis leading to the initial PKP (p<0.001). The probability of graft survival was not significantly reduced with multiple repeat PKP compared to the first repeat PKP.
Table 3 Graft clarity v repeat keratoplasty.
| Repeat PKP No | Eyes | Clear | % | Failed | % | Clear grafts (cumulative) | % |
|---|---|---|---|---|---|---|---|
| 1 | 210 | 98 | 46.7 | 112 | 53.3 | 98 | 46.7 |
| 2 | 25 | 13 | 52.0 | 12 | 48.0 | 111 | 52.9 |
| 3 | 5 | 2 | 40.0 | 3 | 60.0 | 113 | 53.8 |
| 4 | 3 | 1 | 33.3 | 2 | 66.7 | 114 | 54.3 |
PKP, penetrating keratoplasty.
Table 4 Survival of repeat penetrating keratoplasty v initial indication for surgery.
| Initial indication | Eyes | After initial repeat PKP | After all repeat PKP | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Clear | % | Failed | % | Clear | % | Failed | % | ||
| PBK/ABK | 62 | 27 | 43.5 | 35 | 56.5 | 30 | 48.4 | 32 | 51.6 |
| Scar | 53 | 23 | 43.4 | 30 | 56.6 | 26 | 49.1 | 27 | 50.9 |
| Keratoconus | 16 | 14 | 87.5 | 2 | 12.5 | 15 | 93.8 | 1 | 6.2 |
| Fuchs' dystrophy | 13 | 2 | 15.3 | 11 | 84.6 | 3 | 23.1 | 10 | 76.9 |
| Therapeutic/tectonic | 12 | 6 | 50.0 | 6 | 50.0 | 8 | 66.7 | 4 | 33.3 |
| Stromal dystrophy | 12 | 11 | 91.7 | 1 | 8.3 | 11 | 91.7 | 1 | 8.3 |
| Others | 42 | 15 | 35.7 | 27 | 64.3 | 21 | 50.0 | 21 | 50.0 |
| Total | 210 | 98 | 46.7 | 112 | 53.3 | 114 | 54.3 | 96 | 45.7 |
PBK/ABK, pseudophakic or aphakic bullous keratopathy; PKP, penetrating keratoplasty.
The relation between associated ocular conditions, concomitant operative procedures, and postoperative complications and graft survival is summarised in table 5. The presence of glaucoma or ocular surface disease was significantly associated with a higher rate of graft failure, while neovascularisation was not. Concomitant glaucoma surgery was a significant risk factor for graft failure, but simultaneous cataract surgery was not. Postoperative complications of endothelial graft rejection episodes, persistent epithelial defects, and microbial keratitis were all significantly associated with an increased risk of graft failure.
Table 5 Survival of repeat keratoplasty v risk factors.
| Risk factors | No | Clear | % | Failed | % | p Value* |
|---|---|---|---|---|---|---|
| Associated ocular conditions | ||||||
| Glaucoma† | 104 | 37 | 35.6 | 67 | 64.4 | <0.001 |
| Ocular surface disease | 96 | 36 | 37.5 | 60 | 62.5 | <0.001 |
| Neovascularisation | 36 | 16 | 44.4 | 20 | 55.6 | 0.20 |
| Concomitant operative procedures | ||||||
| Lens extraction | 29 | 13 | 44.8 | 16 | 55.2 | 0.32 |
| Glaucoma procedure | 14 | 3 | 21.5 | 11 | 78.6 | 0.012 |
| Postoperative complications | ||||||
| Endothelial graft rejection | 53 | 15 | 28.3 | 38 | 71.7 | <0.001 |
| Persistent epithelial defect | 35 | 7 | 20.0 | 28 | 80.0 | <0.001 |
| Microbial keratitis | 30 | 9 | 30.0 | 21 | 70.0 | 0.005 |
*Probability of graft survival v eyes without the same risk factor.
†Includes 68 eyes with pre‐existing glaucoma and 36 eyes with new onset postoperative glaucoma.
The final visual outcome after repeat PKP is summarised in table 6. Overall, 29.6% of eyes achieved a final visual acuity greater than 20/200, while 4.8% were 20/40 or better. The best visual prognosis was in eyes with an original diagnosis of stromal dystrophy and keratoconus, in which a final visual acuity greater than 20/200 was achieved in 75.0% and 68.8% of eyes, respectively, and 25% of eyes achieved a final visual acuity of 20/40 or better. Less than 25% of eyes with an original diagnosis of PBK/ABK, corneal scar, and Fuchs' dystrophy obtained visual acuity better than 20/200 after repeat PKP.
Table 6 Visual outcome v original indication for keratoplasty.
| Visual acuity | All cases | PBK/ABK* | Scar | Fuchs' dystrophy | Keratoconus | Tectonic/therapeutic | Stromal dystrophy | Others | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No | Cum % | No | Cum % | No | Cum % | No | Cum % | No | Cum % | No | Cum % | No | Cum % | No | Cum % | |
| ⩾20/40 | 10 | 4.8 | 2 | 3.2 | 0 | 0 | 0 | 0 | 4 | 25.0 | 1 | 8.3 | 3 | 25.0 | 0 | 0 |
| 20/50–20/160 | 52 | 29.6 | 13 | 24.2 | 10 | 18.9 | 2 | 15.4 | 7 | 68.8 | 5 | 50.0 | 5 | 75.0 | 10 | 23.9 |
| CF‐20/200 | 90 | 68.1 | 28 | 69.4 | 26 | 67.9 | 6 | 61.5 | 3 | 91.7 | 3 | 75.0 | 4 | 100.0 | 20 | 71.4 |
| HM | 36 | 85.2 | 13 | 90.3 | 11 | 88.7 | 5 | 100.0 | 0 | 91.7 | 2 | 91.7 | 0 | 100.0 | 5 | 83.3 |
| LP | 15 | 92.4 | 5 | 98.4 | 2 | 92.5 | 0 | 100.0 | 2 | 100.0 | 1 | 100.0 | 0 | 100.0 | 5 | 95.2 |
| NLP | 7 | 100.0 | 1 | 100.0 | 4 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 2 | 100.0 |
| Total | 210 | 62 | 53 | 13 | 16 | 12 | 12 | 42 | ||||||||
*Pseudophakic/aphakic bullous keratopathy.
Discussion
The ratio of repeat to initial keratoplasty is a function of not only the failure rate of initial grafts, but the willingness to repeat the procedure. Although graft failure rates range from a low of 8% for keratoconus to a high of 57% for therapeutic/tectonic grafts in our patient population,24,25,26,27 the number of repeat PKP did not exceed 12.3% for any surgical indication, and only constituted 4.2% of total cases of initial PKP during the same time period. This low ratio of repeat to initial keratoplasty reflected caution for performing repeat PKP in a setting where the prognosis for successful surgery was often guarded and many patients were on the eye bank waiting list for initial surgery.23
Historically, repeat PKP have had a poorer prognosis for survival than initial keratoplasty. Repeat PKP share the same risk factors for graft failure as the initial keratoplasty with respect to the recipient diagnosis, but additional risk factors have been acquired since the original procedure such as increased age in all cases, and glaucoma escalation, development of neovascularisation, and worsening of ocular surface disease in many cases.2,7,19,21 In a direct comparison of initial and repeat keratoplasty performed on 696 patients by a single surgeon, Weisbrod and associates21 reported a significant difference in 5 year survival (64.6% v 45.6%, respectively; p<0.001). The 5 year Kaplan‐Meier survival rate for all cases in the present series of 49% is comparable to other series in which there was a mean 5 year survival rate of 48%5,7,20,21 (range 30%20 to 66%5). There was considerable variation in overall graft survival between surgical indications in our series, with more than 90% of grafts remaining clear after repeat PKP in eyes with keratoconus and stromal dystrophies, approximately 50% remaining clear in eyes with PBK/ABK and corneal scars, and less than 25% remaining clear in eyes with Fuchs' dystrophy. As in previous studies,2,7,19,21,28 the presence of preoperative ocular surface disease, the performance of simultaneous glaucoma surgery, the presence of postoperative glaucoma, the postoperative development of a persistent epithelial defect or microbial keratitis, or the occurrence of an endothelial rejection episode all contributed to an increased risk of graft failure after repeat PKP in our patients. Conversely, the presence of neovascularisation or simultaneous cataract surgery did not significantly increase the risk of graft failure.
Unfortunately, the prognosis for visual outcome after repeat PKP was poor with less than 5% of eyes achieving a final visual acuity of 20/40 or better, and less than 30% of eyes obtaining vision that was better than 20/200. Our findings are consistent with three major Western studies in which the percentage of eyes with a visual acuity of 20/40 or better ranged from 3.6% to 9.0%, and less than 25% obtained vision that was better than 20/200.2,4,7 As expected, eyes with stromal dystrophy and keratoconus, in which the prognosis for graft survival was excellent and other conditions compromising visual potential are usually absent, had a much better visual prognosis than eyes with diagnoses associated with poor graft survival and other associated conditions, such as macular oedema or optic atrophy, which further compromised the visual prognosis, even if graft clarity could be maintained.
King Khaled Eye Specialist Hospital Cornea Transplant Study Group
Physician members: Ali A. Al‐Rajhi, MD, FRCS; Klaus Teichmann, MD; Abdul‐Elah Al‐Towerki, MD. Data coordination staff: Ritzchie O. Burog, BSSA; Barbara Elias, CEBT; El‐Sayed Gonnah, CEBT; Jamila Al‐Shahrani, BSC; Abid Al‐Talhi, CEBT. Biostatistician: Yaser Shaheen, BSSA.
Abbreviations
ABK - aphakic bullous keratopathy
KKESH - King Khaled Eye Specialist Hospital
PBK - pseudophakic bullous keratopathy
PKP - penetrating keratoplasty
Footnotes
Competing interests: none declared
References
- 1.Cowden J, Kaufman H E, Polack F M. The prognosis of keratoplasty after previous graft failures. Am J Ophthalmol 197478523–525. [DOI] [PubMed] [Google Scholar]
- 2.Robinson C H. Indications, complications, and prognosis for repeat penetrating keratoplasty. Ophthalmic Surg 19791027–34. [PubMed] [Google Scholar]
- 3.Volker‐Dieben H J, Kok‐van Alphen C C, Lambergen Q.et al Different influences on corneal graft survival in 539 transplants. Acta Ophthalmol 198260190–202. [DOI] [PubMed] [Google Scholar]
- 4.Insler M S, Pechous B. Visual results in repeat penetrating keratoplasty. Am J Ophthalmol 198615371–375. [DOI] [PubMed] [Google Scholar]
- 5.MacEwen C J, Khan Z U, Anderson E.et al Corneal re‐graft: indications and outcome. Ophthalmic Surg 198819706–712. [PubMed] [Google Scholar]
- 6.Rapuano C J, Cohen E J, Brady S E.et al Indications for and outcomes of repeat penetrating keratoplasty. Am J Ophthalmol 1990109689–695. [DOI] [PubMed] [Google Scholar]
- 7.Kirkness C M, Ezra E, Rice N S.et al The success and survival of repeat corneal grafts. Eye 1990458–64. [DOI] [PubMed] [Google Scholar]
- 8.Damji K F, Rootman J, White V A.et al Changing indications for penetrating keratoplasty in Vancouver, 1978–87. Can J Ophthalmol 199025243–248. [PubMed] [Google Scholar]
- 9.Sharif K W, Casey T A. Changing indications for penetrating keratoplasty, 1971–1990. Eye 19937485–488. [DOI] [PubMed] [Google Scholar]
- 10.Flowers C W, Chanq K Y, McLeod S D.et al Changing indications for penetrating keratoplasty, 1989–1993. Cornea 199514583–588. [PubMed] [Google Scholar]
- 11.Price J W, Jr, Whitson W E, Johns S.et al Risk factors for corneal graft failure. J Refract Surg 199612134–143. [DOI] [PubMed] [Google Scholar]
- 12.Eye Bank Association of America Corneal transplant recipient diagnosis reports 1992–1997. Washington DC: Eye Bank Association of America
- 13.Liu E, Slomovic A R. Indications for penetrating keratoplasty in Canada, 1986–1995. Cornea 199716414–419. [PubMed] [Google Scholar]
- 14.Lois N, Kowal V O, Cohen E J.et al Indications for penetrating keratoplasty and associated procedures, 1989–1995. Cornea 199716623–629. [PubMed] [Google Scholar]
- 15.Ramsay A S, Lee W R, Mohammed A. Changing indications for penetrating keratoplasty in the west of Scotland from 1970 to 1995. Eye 199711357–360. [DOI] [PubMed] [Google Scholar]
- 16.Cursiefen C, Kuchle M, Naumann G O. Changing indications for penetrating keratoplasty: histopathology of 1,250 corneal buttons. Cornea 199817468–470. [DOI] [PubMed] [Google Scholar]
- 17.Patel N P, Kim T, Rapuano C J.et al Indications for and outcomes of repeat penetrating keratoplasty, 1989–1995. Ophthalmology 2000107719–724. [DOI] [PubMed] [Google Scholar]
- 18.Maeno A, Naor J, Lee H M.et al Three decades of corneal transplantation: indications and patient characteristics. Cornea 2000197–11. [DOI] [PubMed] [Google Scholar]
- 19.Bernudsky V, Blum‐Hareuveni T, Rehany U.et al The profile of repeated corneal transplantation. Ophthalmology 2001108461–469. [DOI] [PubMed] [Google Scholar]
- 20.Cosar C B, Sridhar M S, Cohen E J.et al Indications for penetrating keratoplasty and associated procedures, 1996–2000. Cornea 200221148–151. [DOI] [PubMed] [Google Scholar]
- 21.Weisbrod D J, Sit M, Naor J.et al Outcomes of repeat penetrating keratoplasty and risk factors for graft failure. Cornea 200322429–434. [DOI] [PubMed] [Google Scholar]
- 22.Tuppin P, Poinard C, Loty B.et al Risk factors for corneal regraft in patients on the French waiting list. Cornea 200423704–711. [DOI] [PubMed] [Google Scholar]
- 23.al‐Towerki A, al‐Rajhi A A, Wagoner M D. Changing indications for keratoplasty at the King Khaled Eye Specialist Hospital (1983–2002). Cornea 200423584–588. [DOI] [PubMed] [Google Scholar]
- 24.Wagoner M D, Gonnah E S. Graft survival after prolonged storage in Optisol‐GS. Cornea 2005. (in press) [DOI] [PubMed]
- 25.Mahmood M, Wagoner M D. Penetrating keratoplasty in eyes with keratoconus and vernal keratoconjunctivitis. Cornea 200019468–470. [DOI] [PubMed] [Google Scholar]
- 26.al‐Swailem S A, Al‐Rajhi A A, Wagoner M D. Penetrating keratoplasty for macular corneal dystrophy. Ophthalmology 2005112220–224. [DOI] [PubMed] [Google Scholar]
- 27.Wagoner M D, Al‐Rajhi A A. Ophthalmology in the Kingdom of Saudi Arabia. Arch Ophthalmol 20011191539–1541. [DOI] [PubMed] [Google Scholar]
- 28.Waring G O., III The 50‐year epidemic of pseudophakic corneal edema (editorial). Arch Ophthalmol 1989107657–659. [DOI] [PubMed] [Google Scholar]