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Abstract
Aims: To investigate the major shifts in the ratio of lamellar keratoplasty (LKP) to penetrating keratoplasty (PKP) and in the preoperative indications for each procedure.
Methods: Medical records of patients who received LKP and/or PKP at Shandong Eye Institute between 1996 and 2007 were categorised and reviewed. The time period was divided into intervals of 1996–8, 1999–2001, 2002–4 and 2005–7.
Results: A total of 4346 patients (5316 eyes) with integrated clinical records were included in the study. LKPs and PKPs were performed on 1558 eyes (29.3%) and 3758 eyes (70.7%), respectively. Within the first 3-year interval, the top three indications for LKP were chemical burns, keratoconus and corneal dermoid; the top reasons for PKP were viral keratitis, suppurative keratitis and corneal scarring. Within the last interval, suppurative keratitis, keratoconus and viral keratitis became most common indications for LKP and suppurative keratitis, viral keratitis and bullous keratopathy for PKP. The ratio of LKP to PKP operations tended to increase.
Conclusion: Following proper indications, the use of LKP has increased in number in north China and has become particularly frequent in the management of corneal infections, keratoconus, corneal degeneration, and stromal dystrophy.
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Corneal transplantations are the main procedures performed to treat corneal blindness. Traditionally, penetrating keratoplasty (PKP) has been the procedure selected for corneal diseases such as suppurative keratitis, keratoconus and corneal stromal dystrophy. However, immune rejection, which can lead to graft opacity, remains a major problem after PKP. Even “normal” graft may have chronic corneal allograft dysfunction.1 With the accumulation of knowledge on corneal diseases, corneal endothelia and corneal surgery procedures, as well as the development of microsurgical technology, lamellar keratoplasty (LKP) has become more valued. Although today it is well accepted that LKP should be preferred over PKP in as many cases without major problems with the corneal endothelia as it is possible to prevent endothelium-related problems such as immune rejection and chronic corneal allograft dysfunction, we have not yet seen a clinical report with a large number of cases to support the existence of this shift. To track this spontaneous change in procedure preference, we retrospectively reviewed the corneal transplantation cases from Shandong Eye Institute over 12 years and evaluated procedural shifts and indications for each operative procedure.
Methods
Medical records of patients who received corneal transplantation at Shandong Eye Institute, including Qingdao Eye Hospital and Shandong Eye Hospital, from January 1996 to December 2007 were reviewed. Shandong Eye Institute is an important clinical centre for corneal diseases in north China, with patients mainly from across the northern provinces. The corneal diseases were categorised into suppurative keratitis (fungal, bacterial and amoebic infections), viral and other keratitis (viral infection, Mooren ulcer and stromal keratitis), corneal degeneration, dystrophy and congenital anomaly, keratoconus, corneal injury and others.2
All data were divided into four time intervals according to the admission date: January 1996 to December 1998, January 1999 to December 2001, January 2002 to December 2004 and January 2005 to December 2007. Clinical features of patients, preoperative diagnosis and surgical procedure were collected. Proportions of LKP versus PKP within each interval and major preoperative diagnoses were analysed.
The χ2 test was used for statistical analysis with SPSS10.0. A p value of less than 0.05 was considered statistically significant.
Results
A total of 4346 patients (5316 eyes) were included. They were 1312 women and 3034 men, aged from 6 months to 91 years. LKP and PKP were performed on 1558 eyes (29.3%) and 3758 eyes (70.7%), respectively.
Changes in procedural preference
There were 982 corneal transplantations including 236 LKPs (24.0%) and 746 PKPs (76.0%) during the period 1996–8, 1300 transplantations including 352 LKPs (27.1%) and 948 PKPs (72.9%) during 1999 and 2001, 1641 transplantations including 438 LKPs (26.7%) and 1203 PKPs (73.3%) during 2002 and 2004, and 1393 transplantations including 532 LKPs (38.2%) and 861 PKPs (61.8%) during 2005 and 2007 (χ2 = 74.79, p = 0.00). The proportions of LKP to PKP increased (figs 1, 2).
Proportions of lamellar keratoplasty (LKP) and penetrating keratoplasty (PKP).
Number of lamellar keratoplasties (LKP) and penetrating keratoplasties (PKP) by year.
Trends in major preoperative diagnoses
Over the 12 years, 1631 eyes with suppurative keratitis underwent corneal transplantation, including 1046 eyes (64.1%) with fungal keratitis, 563 (34.5%) with bacterial keratitis and 22 (1.3%) with amoebic keratitis. Across the four time intervals, LKP was given in 7.5%, 33.7%, 29.9% and 36.9% of eyes with fungal infection (χ2 = 47.70, p<0.01), 7.6%, 32.3%, 30.8% and 27.1% of those with bacterial infection (χ2 = 23.57, p<0.01) and 0%, 0%, 11.1% and 75.0% of those with amoebic infection (χ2 = 9.34, p = 0.009), respectively (table 1, figs 3–6).
Number of lamellar keratoplasties performed for major corneal problems.
Number of penetrating keratoplasties performed for major corneal problems.
Proportions of lamellar keratoplasties (LKP) and penetrating keratoplasties (PKP) for fungal keratitis.
Number of lamellar keratoplasties (LKP) and penetrating keratoplasties (PKP) for fungal keratitis.
Percentage of lamellar keratoplasty performed among eyes with varied corneal problems
In addition to suppurative keratitis, there were also 756 eyes with viral and other types of keratitis that were treated by corneal transplantation, including 630 eyes (83.3%) with viral keratitis, 105 eyes (13.9%) with Mooren ulcers and 21 eyes (2.8%) with stromal keratitis. Across the four time intervals, LKP treatment accounted for 3.0%, 6.1%, 3.2% and 26.6% in eyes with viral infection (χ2 = 70.29, p = 0.000), 100%, 100%, 97.4% and 92.3% in eyes with Mooren ulcers (χ2 = 3.40, p = 0.33) and 0%, 11.1%, 20.0% and 42.9% in eyes with stromal keratitis (χ2 = 2.24, p = 0.326), respectively.
Among the 351 eyes undergoing corneal transplantation for corneal dysfunctions, 130 eyes (37.0%) had corneal degeneration, 128 (36.5%) had corneal dystrophy (30 eyes with endothelial dystrophy and 98 with stromal dystrophy), and 93 (26.5%) had corneal dermoid. Across the four time intervals, 63.3%, 71.4%, 73.8% and 86.7% of eyes with corneal degeneration (χ2 = 4.355, p = 0.226), 0%, 3.8%, 37.8% and 36.7% of eyes with corneal stromal dystrophy (χ2 = 27.26, p = 0.00) and 100%, 100%, 100% and 78.3% of eyes with corneal dermoid (χ2 = 11.15, p = 0.011) were treated by LKP, respectively. All corneal endothelial dystrophy cases received PKP.
Moreover, 674 eyes with keratoconus underwent keratoplasty including epikeratophakia. LKP was performed in 62.4%, 23.8%, 24.2% and 61.4% of the keratoconus eyes in the four intervals, respectively (χ2 = 97.83, p<0.00; figs 7, 8).
Proportions of each corneal transplantation procedure for keratoconus. EP, epikeratophakia; LKP, lamellar keratoplasty; PKP, penetrating keratoplasty.
Numbers of each corneal transplantation procedure for keratoconus. EP, epikeratophakia; LKP, lamellar keratoplasty; PKP, penetrating keratoplasty.
Regarding the 1904 eyes with corneal injury and other disorders, 411 eyes (21.6%) had corneal burns (mostly chemical burns), 162 (8.5%) had mechanical injury, 353 (8.5%) had bullous keratopathy, 394 (20.7%) had corneal scarring, 246 (12.9%) had graft opacity, and 338 (17.8%) had other problems. Across the four time intervals, 62.2%, 60.2%, 57.7% and 44.1% of eyes with corneal burns (χ2 = 6.16, p = 0.10), 13.3%, 2.0%, 10.3% and 13.6% of eyes with mechanical injury (χ2 = 4.68, p = 0.197), 9.1%, 3.7%, 2.5% and 11.9% of eyes with bullous keratopathy (χ2 = 9.88, p = 0.02), 2.9%, 7.6%, 14.5% and 24.1% of eyes with corneal scarring (χ2 = 9.88, p = 0.02), 11.6%, 22.2%, 10.7% and 27.7% of eyes with graft opacity (χ2 = 9.04, p = 0.03) and 29.5%, 19.1%, 6.8% and 28.0% of eyes with other corneal problem (χ2 = 17.77, p = 0.00) were treated by LKP, respectively.
Trends in indications for LKP
Among the 236 LKPs performed between 1996 and 1998, the four leading preoperative diagnoses were corneal burns (61 eyes, 25.8%), keratoconus (58 eyes, 24.6%), corneal dermoid (23 eyes, 9.7%) and Mooren ulcer (13 eyes, 5.5%). Between 1999 and 2001, the leading preoperative diagnoses in 352 eyes treated by LKP became fungal keratitis (91 eyes, 25.9%), corneal burns (62 eyes, 17.6%), bacterial keratitis (43 eyes, 12.2%) and kerotoconus (40 eyes, 11.4%). Of the 438 LKPs between 2002 and 2004, the major indications were fungal keratitis (98 eyes, 22.4%), corneal burns (82 eyes, 18.7%), bacterial keratitis (57 eyes, 13.0%) and keratoconus (48 eyes, 11.0%). Of the 532 LKPs between 2005 and 2007, keratoconus (132 eyes, 24.8%) ranked first in the indications, followed by fungal keratitis (106 eyes, 19.9%), viral keratitis (41eyes, 7.7%) and bacterial keratitis (38 eyes, 7.1%; fig 3).
Discussion
In our current study, we surveyed the spontaneous trend in procedural preference of corneal transplantation in north China over a 12-year time period and analysed the reasons for the trend. It appeared that the proportion of LKPs kept increasing. Important changes occurred in the indications for corneal transplantation.
Trends in procedural preference
The proportion of LKPs performed for corneal diseases presenting with no major problems in the endothelial cells, such as fungal keratitis, bacterial keratitis and stromal dystrophy, kept increasing, especially for fungal keratitis with the percentage from 7.5% in 1996–8 to 34.9% in 2005–7. This trend was mainly due to changes in our knowledge of fungal keratitis. We used to believe that LKP should not be used in the treatment of fungal keratitis for fear that the fungal hyphae would grow vertical to the corneal stroma, through the Descemet membrane, and into the anterior chamber. We previously reported a pathological study on 108 corneal buttons obtained during PKP for fungal keratitis and found that different fungal species had different infection features and growth patterns,3 which was supported by animal studies.4 Based on these ideas, more LKPs were performed for fungal keratitis not controlled with medications. Vision achieved after LKP was similar to that after PKP, yet with the obviously lower risks from potential complications and rejection.567
The proportion of LKPs (including epikeratophakia) for keratoconus decreased in early years and then increased significantly in this study. The reasons for the decrease may be related to vision-reducing graft–host interface problems after LKP, which made patients choose PKP to regain good vision as soon as possible. Meanwhile, we knew little about chronic corneal allograft dysfunction and assumed that the graft would survive as long as no rejection was observed. Since the risk of rejection was lower for keratoconus patients, surgeons favoured PKP. Moreover, LKP in early years was actually epikeratophakia, which carried a high risk of complications, such as secondary glaucoma. Later, the increased knowledge of chronic corneal allograft dysfunction turned our attention to LKP. Chronic dysfunction was first reported in renal allografts and other solid organ transplants. Chronic corneal allograft dysfunction was a phenomenon in corneal allografts displaying a gradual deterioration of graft function months to years after PKP for no particular reason, eventually leading to graft failure, with characteristic image and histological changes.8 Although PKP presented better short-term results than LKP, its long-term survival rate was not satisfying due to immune rejection and chronic corneal allograft dysfunction. Armitage et al1 established a model that chronicled endothelial cell loss. According to this model, if the density of the graft endothelial cells was 2500 cells/mm2 after PKP, graft opacity caused by the loss of endothelial cells would occur in about 28 years. Pramanik et al9 investigated 84 patients (112 eyes) with keratoconus treated by PKP and observed graft opacity in 6.3% of the eyes in the follow-up of 13.8 years. In a report of 22 cases with PKP for keratoconus and a follow-up of 13.3 years, the mean density of the graft endothelial cells was only 695 cells/mm2 at the last visit, which might lead to graft opacity and failure.10 Fortunately, LKP has a low risk of rejection and chronic corneal allograft dysfunction. Meanwhile, the development of microsurgical techniques, such as deep anterior LKP, enables patients to achieve favourable vision after surgery.1112 In this study, the corneal lamellae were removed as deep as possible until there was little stromal tissue left with the endothelia. The vacuum trephine was a key device for controlling the pealing depth during the LKP procedures, and no perforation occurred. Therefore, the long-term influence of chronic corneal allograft dysfunction should not be neglected. It is recommended that deep anterior LKP be performed, when necessary, as early as possible for keratoconus patients to save their own endothelia.
Trends in indications for keratoplasty
The leading two indications for LKP in south China from 1965 to 1985 were Mooren ulcer and chemical burns.13 In the current study, suppurative keratitis was the top reason for LKP in north China in the recent 12 years, and the indications expanded. Between 1996 and 1998, LKP was performed for chemical burns, keratoconus and corneal dermoid, and very few for other corneal problems. Since that time period, increasing numbers of fungal keratitis and bacterial keratitis patients were treated by LKP. Between 2005 and 2007, LKP was also used to treat stromal dystrophy and amoebic keratitis. The changes in the reasons for LKP are related to the improved understanding of the preoperative diseases and the development of microsurgical technology.14
The “dramatic” increase in LKP for Acanthamoeba keratitis was simply due to the small number of cases. Only 22 eyes were diagnosed as amoebic keratitis in this study. We are still trying to figure out why there are so few such cases in north China, and a more reasonable curve may be found after a longer investigation.
Furthermore, the findings of viral latency led to more LKPs. Herpes simplex virus 1 stayed latent not only in the trigeminal ganglia but also in the corneal stroma,15 which indicates that removing the stroma would be a way to prevent viral recurrence. Therefore, we started to perform LKP in carefully chosen cases and obtained satisfying results. Recently, it was reported that corneal stroma, as well as the trigeminal ganglia, was neuro-derived tissue,1617 which gives a strong support to our previous finding.15
Over the past 12 years, there has been a trend of increased LKP preference in north China. Since PKP is associated with short- and long-term problems, such as immune rejection and chronic corneal allograft dysfunction, LKP appears to be prosperous in corneal transplantations, as it can preserve autologous corneal endothelia, produce few complications and result in improved visual acuity.
Acknowledgments
We would like to thank P Lin, for her editorial assistance.
REFERENCES
Footnotes
Funding Supported by the National Natural Science Foundation of China (30630063 & 30271394), Department of Science and Technology of Shandong Province (2004GG2202154) and Qingdao Municipal Science and Technology Bureau (02KGYSH-01).
Competing interests None.
Provenance and Peer review Not commissioned; externally peer reviewed.
Ethics approval Ethics approval was provided by Shandong Eye Institute.
Patient consent Obtained.