- Research article
- Open Access
- Open Peer Review
This article has Open Peer Review reports available.
Indications and outcome of repeat penetrating keratoplasty in India
© Vanathi et al; licensee BioMed Central Ltd. 2005
Received: 27 December 2004
Accepted: 02 November 2005
Published: 02 November 2005
Repeat penetrating keratoplasty is quite often required as there is high chance of failure of the primary graft particularly in the developing world. We planned a study to analyze the indications and outcome of repeat penetrating keratoplasty in a tertiary care centre in India.
A retrospective analysis of all the patients who underwent repeat penetrating keratoplasty, between January 1999 and December 2001 was performed. The parameters evaluated were indication for the primary penetrating keratoplasty, causes of failure of the previous graft, and final visual outcome and clarity of the repeat corneal grafts.
Of fifty-three eyes of 50 patients with repeat penetrating keratoplasty (three patients underwent bilateral corneal regrafts), 37 eyes had undergone one regraft each, 14 eyes two regrafts and two eyes had three regrafts. The follow-up of the patients ranged from one to three years. The most common primary etiologic diagnosis was vascularized corneal scars (66%), of which the scars related to infection were most common (68.5%). Twenty-eight regrafts (52.8%) remained clear at a mean follow-up of 1.54 ± 0.68 years, of which 25 were single regrafts (89.3%). The commonest cause of failure of regraft was infection to the corneal graft (recurrence of herpetic infection in 9 eyes and perforated graft ulcers in 3 eyes). Three (18.6%) of the 16 eyes with multiple corneal regrafts achieved a BCVA of 6/60. Overall, only five eyes (all with single regraft) achieved a BCVA of 6/18 or better at the end of follow-up.
Graft infection is the leading cause of failure of repeat keratoplasty in this part of the world. Prognosis for visual recovery and graft survival is worse in eyes undergoing multiple regrafts.
Corneal graft failure constitutes a common indication for penetrating keratoplasty [1–20]. There are a few studies in literature which have reported the indications and outcome of corneal regrafts [21–27]. The primary indications for repeat corneal transplantation show a changing trend. Aphakic and pseudophakic bullous keratopathy were the common primary indications for regrafts in developed countries in previous studies [22–26], others being, infectious keratitis  and corneal dystrophies [22, 25]. However, a more recent study on the profile of repeat keratoplasty  identified vascularized corneal scar as the most common primary indication for corneal regrafting. The paucity of studies on repeat keratoplasty from developing countries prompted us to evaluate the indications and outcome of repeat keratoplasty at a tertiary eye care referral centre.
We retrospectively reviewed the records of 50 patients of corneal regrafts performed at the Cornea services of Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, during the period from January 1999 to December 2001. Of all these 50 patients, 32 patients (64%) were from rural and peri-urban areas and 18 (36%) were from urban areas.
The parameters evaluated were the patient's age, gender, indication for the primary corneal transplan tation, duration of follow-up, number of regrafts, associated procedures performed and outcome of corneal regrafts. More than one corneal regraft was considered as a multiple regraft. Details of previous grafts in cases of multiple regrafts were collected from old records wherever available. Graft outcome was defined in terms of the clarity over a period of time till last follow-up or graft failure, whichever was earlier. Graft was considered to be clear if the clarity was of grade 3 or grade 4. By grade 4 clarity, we mean an absolutely clear graft with good visualization of the iris details behind it. By grade 3 clarity, we mean a graft with minimal haze but still with reasonably good visualization of the iris details.
Allograft rejection was diagnosed by the presence of endothelial or epithelial rejection line or both and corneal edema with anterior chamber reaction. Corneal graft failure was diagnosed when irreversible graft edema was present with or without vascularization or scarring of the graft. Intraocular pressure greater than 21 mm Hg on two separate occasions was taken as secondary glaucoma.
Postoperatively patients were prescribed topical betamethasone sodium phosphate 0.1% and ciprofloxacin 0.3% QID each and ocular lubricants (polyvinyl alcohol) QID. Patients with healed herpetic keratitis were given oral acyclovir 400 mg twice a day for 1 year after keratoplasty. The follow up schedule after the surgery was daily from day 1 till epithelial healing, 1 week, 1 month, 3 months, 6 months, 1 year and yearly thereafter. The duration of follow-up was taken as the time between the last regraft and the final follow-up. The outcome of the surgery was analyzed statistically using paired 't' test and p-value smaller than 0.05 was considered as statistically significant.
Sixty eight patients had undergone corneal regrafts at our centre during the study period. Of these, 50 patients (73.5 %) (41 males and 9 females) had a regular follow-up with us of which, 3 patients had undergone bilateral corneal regrafts and these were included in the study (N = 53 eyes). The primary keratoplasty was performed at our centre in 39 eyes of 36 patients and 14 patients were referred from other centres after failure of the primary graft.
The mean age of the patients at the time of repeat penetrating keratoplasty was 45.2 ± 16.5 years. The mean follow-up after regraft was 1.54 ± 0.68 years. Of a total of 53 eyes, 37 eyes had one corneal regraft, 14 had two corneal regrafts and two eyes had undergone three regrafts each (i.e. multiple regrafts in 16 eyes). Forty-eight eyes had undergone other associated intraocular procedures such as goniosynechiolysis (32 eyes), iridectomy with pupilloplasty (7 eyes), cataract extraction (7 eyes) and anterior vitrectomy (11 eyes) at the time of regraft.
Indications for primary corneal transplantation in corneal regrafts
No of eyes (%) (n = 53)
Single regraft (n = 37)
Multiple Regraft (n = 16)
Vascularised corneal scars
Healed infectious keratitis (non-herpetic)
Steven Johnson's syndrome
Aphakic Bullous Keratopathy
Pseudophakic Bullous Keratopathy
The failure of primary graft was attributable to poor ocular surface in 18 eyes (33.9%), recurrence of herpetic keratitis in 8 eyes (15%), perforated graft ulcers in 4 (7.5%), scarring due to graft infection in 4 (7.5%), allograft rejection in 7 eyes (13.2%), endothelial decompensation in 8 eyes (15 %) and raised intraocular pressure in 4 eyes (7.5%). Since a high proportion of the grafts failed due to poor ocular surface, all these eyes were put on intensive (1 hourly) preservative free lubricants and repeat grafting was performed only after these eyes attained a reasonably good ocular surface. Two eyes with failed primary graft and ocular surface problems required entropion surgery and in two eyes permanent punctual plugs were inserted before regraft.
After repeat graft, these eyes were prescribed 1 hourly preservative free lubricant for 3 months and QID later along with topical chloramphenicol and topical dexamethasone QID each for 3 months and BD each later.
Outcome of corneal regrafting surgery
No of eyes (n = 53)
1 regraft (n = 37)
2 regraft (n = 14)
3 regraft (n = 2)
Clear regrafts (n = 28)
Failed regrafts (n = 25)
p value (Paired 't' test)
0.001 (statistically significant)
0.006 (not significant)
Visual Acuity of single Vs multiple regrafts at last follow up
Clear regrafts (n = 28)
BCVA 6/18 or better (n = 5)
BCVA Less than 6/18 (n = 23)
Single regrafts (n = 25)
Multiple regrafts (n = 3)
Causes of suboptimal visual outcome (post-refraction) in regrafts that remained clear (grade 3/4) was poor ocular surface (9 eyes), post penetrating keratoplasty astigmatism (6 eyes), macular scarring (5 eyes), treated graft rejection (4 eyes) and post-penetrating keratoplasty glaucoma (4 eyes).
Repeat corneal grafts remain a drain on existing resources for corneal transplantation and the rise in the number of regrafts parallels the rise in number of primary keratoplasties. Several studies [1–20] on the indications for penetrating keratoplasty have cited variable figures comprising the proportion of regrafts varying from 6.6% to 41%. On the basis of these studies it is apparent that corneal regrafts show an increasing trend among indications for penetrating keratoplasty. Dandona et al  studied the indications for penetrating keratoplasty in India and reported regrafts as the second most common indication for penetrating keratoplasty in India (17.1%), next only to corneal scarring of varied etiology.
Different success rates and visual outcome in corneal regrafts have been reported in literature [21–27]. Reported percentages of clear regrafts vary from 51% to 74% in the earlier studies [21, 25–27]. In the present study the outcome of repeat penetrating keratoplasty in terms of graft clarity was comparable (52.8%).
Eyes in which repeat keratoplasty was performed necessitated multiple intraocular manipulations like goniosynechiolysis, iridectomy with pupilloplasty, cataract extraction and anterior vitrectomy. Post-keratoplasty glaucoma resulting due to these manipulations is an important factor that can result in graft failure. In the present study, a higher proportion of eyes developed secondary glaucoma (5 out of 25) resulting in graft failure in regrafts in comparison to primary keratoplasty (4 out of 53). This perhaps can be attributed to the fact that repeated surgeries result in greater development of anterior chamber reaction and multiple synechiae, and multiple intraocular manipulations required in regrafts can further be the compounding factor for the same.
Patients who undergo repeat corneal grafts carry the risk of developing variable amount of corneal neovascularisation as was seen in our cases. Corneal neovascularisation is an independent risk factor that can jeopardize the outcome of a successfully performed keratoplasty by causing episodes of graft rejection. However, in contrast to the studies from the developed countries which report graft rejection and recurrence of dystrophies as the main causes for failure of regrafts [22–25], our study highlights that higher prevalence of graft infection including recurrence of previous infection and secondary glaucoma are the leading causes of failure of repeat grafts. Ocular surface problem was the leading cause of failure of primary graft in this study. These eyes were intensively treated with preservative free lubricants to improve the ocular surface before performing regraft. This improved graft survival in these eyes and very few regrafts failed due to ocular surface problems. However, some amount of ocular surface problem persisted in some eyes resulting in mild haze and hence remained the leading cause for suboptimal best corrected visual acuity in these regrafts in spite of reasonably good graft clarity.
Recent studies [25–27] report a visual acuity of 20/40 or better in only 15% to 41% of clear regrafts. Similarly, the present study reports that among the 28 eyes with clear regrafts, a BCVA of 6/18 or better was seen in five eyes only (17.9%) and less than 6/18 in 23 eyes (82.1%). Contrary to few studies [22, 25, 26] reporting that visual prognosis in multiple regrafts to be comparable to that in single regrafts (these regrafts had been performed mainly for pseudophakic bullous keratopathy), Bersudsky et al  had concluded that graft survival and visual outcome is inversely proportional to the number of corneal regrafts. Similarly our study also demonstrates a poorer visual outcome in eyes undergoing multiple regrafts (Table 3). Though the number of eyes with multiple regrafts was small in our study, 13 eyes (81.3%) out of 16 eyes with multiple regrafts failed in our study suggesting that prognosis for graft survival in multiple regrafts seems to be poorer. Owing to the poor graft survival, permanent keratoprosthesis may be a suitable alternative in eyes with multiple regrafts.
The study demonstrates that visual prognosis for multiple corneal regrafting is suboptimal, owing to high chance of graft infection, secondary glaucoma and allograft rejection. However, repeat penetrating keratoplasty should be considered when required depending upon patient's need and motivation and in the absence of any contraindication.
- Arentsen J, Morgan B, Green WR: Changing indications for keratoplasty. Am J Ophthalmol. 1976, 81: 313-318.View ArticlePubMedGoogle Scholar
- Robin JB, Gindi JJ, Koh K, Schanzlin DJ, Rao NA, York KK, Smith RE: An update for indications of keratoplasty. 1979 through 1983. Arch Ophthalmol. 1986, 104: 87-89.View ArticlePubMedGoogle Scholar
- Morris RJ, Bates AK: Changing indications for keratoplasty. Eye. 1989, 3: 455-459.View ArticlePubMedGoogle Scholar
- Mohamadi P, McDonnell JM, Irvine JA, McDonnel PJ, Rao N, Smith RE: Changing indications for penetrating keratolasty, 1984–88. Am J Ophthalmol. 1989, 107: 550-552.View ArticlePubMedGoogle Scholar
- Brady SE, Rapuano CJ, Arentsen JJ, Cohen EJ, Laibson PR: Clinical indications for the procedures associated with penetrating keratoplasty, 1983–88. Am J Ophthalmol. 1989, 108: 118-122.View ArticlePubMedGoogle Scholar
- Damji KF, Rootman J, White VA, Richards JS: Changing indications for penetrating keratoplasty in Vancouver, 1978–87. Can J Ophthalmol. 1990, 25: 243-248.PubMedGoogle Scholar
- Lindquist TD, McGlothan JS, Rotkis WM, Chandler JW: Indications for penetrating keratoplasty: 1980–1988. Cornea. 1991, 10: 210-216.View ArticlePubMedGoogle Scholar
- Hyman L, Wittpen J, Yang C: Indications and techniques for penetrating keratoplasty, 1985–1988. Cornea. 1992, 11: 573-576.View ArticlePubMedGoogle Scholar
- Mamalis N, Anderson CW, Kreisler KR, Lundergan MK, Olson RJ: Changing trends in the indications for penetrating keratoplasty. Arch Ophthalmol. 1992, 110: 1409-1411.View ArticlePubMedGoogle Scholar
- Vail A, Gore SM, Bradley BA, Easty Dl, Rogers CA: Corneal transplantation in the United Kingdon and Republic of Ireland. Br J Ophthalmol. 1993, 77: 650-656.View ArticlePubMedPubMed CentralGoogle Scholar
- Williams KA, Muehlberg SM, Wing SJ, Coster DJ: The Australian Corneal Graft Registry: 1990 to 1992 Report. Aust N Z J Ophthalmol. 1993, 21 (Suppl): 1-48.Google Scholar
- Price FW, Whitson WE, Collins KS, Marks RG: Five-year corneal graft survival: large, single-center patient cohort. Arch Ophthalmol. 1993, 111: 799-805.View ArticlePubMedGoogle Scholar
- Haamann P, Jensen OM, Schmidt P: Changing indications for penetrating keratoplasty. Acta Ophthalmol. 1994, 72: 443-446.View ArticleGoogle Scholar
- Flowers CW, Chang KY, McLeod SD, Irvine JA, McDonnell PJ, Rao N, Smith RE: Changing indications for penetrating keratoplasty 1989–1993. Cornea. 1995, 14: 583-588.View ArticlePubMedGoogle Scholar
- Liu E, Slomovic AR: Indications for penetrating keratoplasty in Canada, 1986–1995. Cornea. 1997, 16: 414-419.View ArticlePubMedGoogle Scholar
- Lois N, Kowal VO, Cohen EJ, Rapuano CJ, Gault JA, Raber IM, Laibson PR: Indications for penetrating keratoplasty and associated procedures, 1989–1995. Cornea. 1997, 6: 623-629.Google Scholar
- Frucht-Pery J, Shtibel H, Solomon A, Siganos CS, Yassur Y, Pe'er J: Thirty years of penetrating keratoplasty in Israel. Cornea. 1997, 16: 16-20.PubMedGoogle Scholar
- Wong TY, Chan C, Lim L, Lim TH, Tan DT: Changing indications for penetrating keratoplasty: a newly developed country's experience. Aust N Z J Ophthalmol. 1997, 25: 145-150.View ArticlePubMedGoogle Scholar
- Dandona L, Ragu K, Janarthanan M, Naduvilath TJ, Shenoy R, Rao GN: Indications for penetrating keratoplasty in India. Indian J Ophthalmol. 1997, 45: 163-168.PubMedGoogle Scholar
- Chen WL, Hu FR, Wang IJ: Changing indications for penetrating keratoplasty in Taiwan from 1987 to 1999. Cornea. 2001, 20: 141-144. 10.1097/00003226-200103000-00004.View ArticlePubMedGoogle Scholar
- Cowden KJ, Kaufman HE, Polack FM: The prognosis of keratoplasty after previous graft failures. Am J Ophthalmol. 1974, 78: 523-555.View ArticlePubMedGoogle Scholar
- Robinson CH: Indications, complications and prognosis for repeat penetrating keratoplasty. Ophthalmic Surg. 1979, 10: 27-34.PubMedGoogle Scholar
- Insler MS, Pechous B: Visual results in repeat penetrating keratoplasty. Am J Ophthalmol. 1986, 102: 371-375.View ArticlePubMedGoogle Scholar
- MacEwen Cj, Khan Zuh, Anderson E, Macewen CG: Corneal re-graft; indications and outcome. Ophthalmic Surg. 1988, 19: 706-712.PubMedGoogle Scholar
- Rapuano CJ, Cohen EJ, Brady SE, Arentsen JJ, Laibson PR: Indications for and outcomes of repeat penetrating keratoplasty. Am J Ophthalmol. 1990, 109: 689-695.View ArticlePubMedGoogle Scholar
- Patel NP, Kim T, Rapuano CJ, Cohen EJ, Laibson PR: Indications for and outcomes of repeat penetrating keratoplasty, 1989–1995. Ophthalmology. 2000, 107: 719-724. 10.1016/S0161-6420(00)00003-8.View ArticlePubMedGoogle Scholar
- Bersudsky V, Blum-Hareuveni T, Rehany U, Rumelt S: The profile of Repeated Corneal Transplantation. Ophthalmology. 2001, 108: 461-469. 10.1016/S0161-6420(00)00544-3.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2415/5/26/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.