National Survey on Corneal Transplantation in Japan

Supplemental Digital Content is Available in the Text.

Abstract

Purpose:

To report the results of a national survey on corneal transplantation in Japan.

Methods:

The Japan Cornea Society and the Keratoplasty Society of Japan conducted a national survey on corneal transplantation performed from 2017 to 2019. Data from various institutions were collected through an online database and subsequently analyzed.

Results:

In total, 4951 cases from 44 facilities were documented. The leading cause of corneal transplantation was corneal edema (CE), which accounted for 39.3% of cases, followed by repeat keratoplasty at 27.7%. Among CE cases, postcataract surgery was the most prevalent (25.1%), followed by postglaucoma surgery (20.8%) and laser iridotomy–induced CE (18.2%). Fuchs endothelial corneal dystrophy was the fourth most common cause (10.9%). Regarding surgical methods, Descemet stripping automated endothelial keratoplasty was the most common, used in 41.3% of procedures, followed by penetrating keratoplasty at 37.1%. Deep anterior lamellar keratoplasty and Descemet membrane endothelial keratoplasty were used in 8.1% and 2.6% of cases, respectively. One year after transplantation, graft clarity was maintained in 80.5% of cases, and regrafting was necessary in 15.2% of instances.

Conclusions:

The national survey reveals that CE is the most frequent indication for corneal transplantation in Japan. Increases in cases from glaucoma surgery and Fuchs endothelial corneal dystrophy were noted among patients with CE. Endothelial keratoplasty, especially Descemet stripping automated endothelial keratoplasty, is now the preferred surgical technique for these transplants.

In recent decades, significant advancements have been made in corneal transplantation techniques. Notably, the development of component lamellar surgeries, such as deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK), has facilitated less-invasive procedures. A prior study from a tertiary referral hospital in Japan indicated a decline in corneal scars secondary to keratitis, in contrast to an increase in endothelial dysfunction following intraocular surgeries.¹ This landscape in corneal transplantation was further evidenced by the large-scale national survey conducted by the Japan Corneal Society (JCS), an open academic society with over 1200 members. The national survey studied cases with corneal edema (CE) that underwent corneal transplantation between 1999 and 2001. The findings published in 2004 highlighted the predominance of postcataract surgery CE and laser iridotomy–induced CE, primarily treated through penetrating keratoplasty (PKP).² To further explore contemporary trends, the JCS and the Keratoplasty Society of Japan (KSJ) recently conducted another comprehensive national survey that examined demographic data, causative diseases, surgical techniques, and early postoperative outcomes. In this study, we report the results of this national survey and compare them with those of previous reports.

METHODS

The study protocol was approved by the Institutional Review Board of Osaka University Hospital (approval no: 21262) and by the review board of participating hospitals or clinics when required. This study was conducted in compliance with the principles of the Declaration of Helsinki. The Japan Corneal Transplantation Study Group in the JCS and the KSJ distributed a questionnaire to each hospital/clinic where JCS members worked. The contents of the questionnaire are shown in Supplemental Digital Content 1 (see Supplemental Table 1, http://links.lww.com/ICO/B774) and Supplemental Digital Content 2 (see Supplemental Table 2, http://links.lww.com/ICO/B775). Members electing to participate were required to record data on each corneal transplant case treated between January 2017 and December 2019. Only corneal transplants that used donor corneas were included. The participating hospitals/clinics are listed in the Supplemental Table 3 (see Appendix, http://links.lww.com/ICO/B773) and include 32 university hospitals, 9 ophthalmic hospitals or clinics, and 3 general hospitals. The patients’ data included demographic characteristics, causes of corneal transplantation, preoperative conditions, associated disorders, types of surgery performed, and postoperative outcomes. The data were recorded electronically and sent to the Research Electronic Data Capture system³ hosted at Osaka University. To the Research Electronic Data Capture is a secure web application for building and managing online surveys and databases. Access to servers and systems is restricted by user accounts and passwords, with a complete audit trail recorded.

RESULTS

Demographic Profile

We received responses from 4951 cases across 44 facilities. The demographic breakdown included 2609 men (52.8%) and 2333 women (47.2%), with a mean age of 67.7 ± 16.5 years (range: 3–97 years). Data for sex and age were missing for 9 and 12 cases, respectively. Preoperative visual acuity ranged from nonlight perception to 20/15, with a median value of 20/200. Distribution of the preoperative visual acuity was as follows: less than 20/2000 (n = 1001, 20.2%), 20/2000–20/200 (n = 1392, 48.3%), 20/200–20/40 (n = 1225, 24.7%), 20/40–20/25 (n = 264, 5.3%), equal or better than 20/20 (n = 43, 0.9%), and not available (n = 26, 0.5%). Most common causative disease of those who had equal or better than 20/20 vision was limbal dermoid (n = 26), followed by noninfectious peripheral keratitis (n = 8). Most such eye received either anterior lamellar keratoplasty (ALK) or DALK (n = 36). Concurrent disorders were present in 46.1% of cases, including cataract (n = 771, 15.6%), postglaucoma surgery (n = 626, 12.7%), medically treated glaucoma (n = 574, 11.6%), and post vitreoretinal surgery (n = 273, 5.5%).

Causative Diseases for Corneal Transplantation

Figure 1 shows the causative diseases for corneal transplantation. CE was the most common, accounting for 39.3% (n = 1941) of cases, followed by repeated keratoplasty (n = 1368, 27.7%). Corneal ectatic diseases (n = 286, 5.8%), predominantly keratoconus (n = 274), and corneal scars secondary to keratitis (n = 327, 6.6%) were also noted.

FIGURE 1.

Causative diseases for corneal transplantation. Data for 10 cases were not available. GVHD, graft-versus-host disease; OCP, ocular cicatricial pemphigoid; SJS, Stevens–Johnson syndrome.

Transforming growth factor beta induced dystrophy was prevalent in corneal dystrophy cases, including lattice (n = 100) and granular corneal dystrophy (n = 26), which makes up 64.1% (n = 127) of cases, followed by other forms of stromal corneal dystrophies such as macular corneal dystrophy and Schnyder corneal dystrophy (n = 42, 21.2%). Infectious keratitis led to transplantation in 279 patients (5.6%), with herpetic keratitis being the most common (n = 102, 36.6%), followed by fungal (n = 76, 27.2%) and bacterial keratitis (n = 63, 22.6%). In eyes with noninfectious keratitis (n = 178), corneal transplantation was performed for peripheral disorders in 122 eyes (68.8%), in which Mooren ulcer and rheumatoid ulcer were common [81 eye (45.4%) and 39 eyes (21.8%), respectively].

Causes of CE

Table 1 presents the analysis of CE causes. Postcataract surgery CE was the most frequent (n = 488, 25.1%), followed by postglaucoma surgery CE (n = 404, 20.8%) and laser iridotomy–induced CE (n = 353, 18.2%). Fuchs endothelial corneal dystrophy (FECD) was the fourth most common cause (n = 212, 10.9%). Among original glaucoma types in CE cases following glaucoma surgery, primary open-angle glaucoma, including normal tension glaucoma, was most common (n = 140, 34.9%), followed by pseudo-exfoliation syndrome (n = 121, 30.2%), and secondary glaucoma (n = 71, 7.7%).

TABLE 1.

Causes of CE

Cause	Number	%
Cataract surgery	488	25.1
Glaucoma surgery	404	20.8
Laser iridotomy	353	18.2
FECD	212	10.9
Vitreoretinal surgery	70	3.6
CMV endotheliitis	55	2.8
Trauma	52	2.7
Uveitis	35	1.8
Other endotheliitis	27	1.4
Forceps injury	26	1.3
Sato surgery*	6	0.3
Other/unknown	213	11.0

^*Anterior–posterior radial keratotomy.

CMV, cytomegalovirus.

Surgical Methods for Corneal Transplantation

The surgical methods employed are shown in Figure 2. Descemet stripping automated EK (DSAEK) was the most common surgical method, accounting for 2041 cases (41.3%). PKP was performed in 1834 cases (37.1%). These 2 methods accounted for ∼78% of all cases. DALK and Descemet membrane endothelial keratoplasty (DMEK) were performed in 8.1% (n = 401) and 2.6% (n = 127), respectively. Epithelial transplantation (ET) using donor corneas was performed in 62 eyes. Femtosecond laser was used in 113 cases (2.3%). The laser was used for DALK (n = 75) or PKP (n = 29) in most cases. PKP was performed most commonly for CE (n = 632), followed by regraft (n = 564), ectatic diseases (n = 114), infectious keratitis (n = 107), and noninfectious keratitis (n = 100).

FIGURE 2.

Types of corneal transplantation performed. Data for 9 cases were not available.

Combined surgery occurred in 23.3% of cases. Cataract surgery was the most common combined procedure (n = 526, 10.6%), followed by lysis of anterior synechiae (n = 178, 3.6%), pupilloplasty (n = 127, 2.6%), intraocular lens implantation (n = 116, 2.3%), vitreoretinal surgery (n = 115, 2.3%), and amniotic membrane transplantation (n = 110, 2.2%).

Table 2 details the surgical methods used for each diagnostic category, showing only those with >100 cases. In cases of CE, >80% underwent EK. In eyes undergone regrafting, PKP was performed in 77.9% of eyes that had previous PKP. EK was performed in eyes that had previous EK and PKP in 74.3% and 21.2%, respectively. Approximately two-thirds of cases involving scars and ectasia were treated with PKP. ALK or DALK was performed in >60% of cases in both dystrophy and noninfectious keratitis categories.

TABLE 2.

Rates of Surgical Methods Used in Each Disease Category

Diseases	PKP (%)	EK (%)	ALK/DALK (%)	ET (%)	Others (%)
CE	15.9	83.9	0.3	0	0
Regraft for previous PKP	77.9	21.2	0.9	0	0
Regraft for previous EK	25.7	74.3	0	0	0
Scar	63.6	0	36.1	0	0.3
Ectasia	68.5	1.7	29.7	0	0
Infectious keratitis	58.1	0.7	37.6	0	3.6
Dystrophy	34.3	3.0	62.1	0.5	0
Noninfectious keratitis	27.5	0.6	68.5	4.5	4.5
Burn/injury	56.6	6.6	25.5	6.6	4.7

Complications

Surgical complications were observed in 217 patients (4.4%). As intraoperative complications, hyphema (n = 58, 1.2%), iris damage (n = 46, 0.9%), vitreous loss (n = 37, 0.7%), graft damage (n = 23, 0.5%), and posterior capsule rupture (n = 16, 0.3%). Early postoperative complications most frequently involved increases in intraocular pressure (n = 45, 9.1%), double chamber formation (n = 285, 5.8%), primary graft failure (n = 122, 2.5%), and infection other than endophthalmitis (n = 85, 1.7%). Graft dislocation and wound dehiscence were noted in 285 (5.8%) and 43 (0.9%) cases, respectively. Immunological rejection occurred in 237 cases (4.8%), with endothelial rejection making up 178 cases. Epithelial and stromal rejection were observed in 17 and 37 patients, respectively.

Graft Conditions 1 Year After Surgery

One year after transplantation, graft status was reported for 4477 cases. Of these, 3604 grafts (80.5%) remained clear. Repeated grafting was necessary in 749 cases (15.2%) during the observation period. There were notable differences in the rates of clear grafts among different surgical methods. Although DALK, DMEK, DSAEK, and PKP showed relatively high clarity rates (90.0%, 85.8%, 86.8%, and 80.4%, respectively), ALK and ET had comparatively lower clarity rates (62.1% and 50.0%, respectively).

DISCUSSION

We gathered data from nearly 5000 cases of corneal transplantation over 3 consecutive years in Japan. The exact number of keratoplasties conducted during this period is unknown; however, data on the number of procedures performed with domestic donors or those provided by the Eye Bank Association of America are available. Considering potential additional sources, such as eye banks outside the Unites States, it is estimated that ∼10,000 corneal transplants were performed during this period. Consequently, our data represent about half of the procedures performed, underscoring that this study reflects recent trends in corneal transplantation in Japan. Notably, the study period was prepandemic, ensuring that the results were not influenced by the disruptions caused by COVID-19.

Globally, numerous studies have examined trends in corneal transplantation, encompassing both hospital-based and national data. National registries of corneal transplantation particularly provide insights into real-world practices. To the best of our knowledge, there are 11 national corneal transplantation registries, including the Australian Corneal Graft Registry,⁴ the United Kingdom Transplant Registry,⁵ the Singapore Eye Bank Registry,⁶ the Netherlands Organ Transplantation Registry,⁷ the Swedish Corneal Transplant Register,⁸ and the European Cornea and Cell Transplantation Registry.^9,10 Eye Bank Association of America^11–14 also provided annual statistics that covers large number of corneal transplants on tissue recovered and used. Four different national surveys, along with our current data, that reported on the incidence of causative diseases for corneal transplantation and surgical procedures are summarized in Table 3.

TABLE 3.

National Corneal Transplantation Surveys

Country/Region	Year	Number	Causative Diseases for Corneal Transplantation (%)
			First	Second	Third
Eye Bank Association of America14	2023	49,110	FECD (36)	Regraft (13)	Other CE (12)
European Cornea and Cell Transplantation Registry13	2021	12,913	FECD (41)	Regraft (16)	PCE (12)
Australian Corneal Graft Registry15	2022	17,065	Keratoconus*	Regraft*	FECD*
Singapore Eye Bank Registry16	2012	NA	PCE (52)	Regraft (14)	FECD (13)
Current study	2025	4951	Regraft (28)	PCE/ACE (10)	Corneal scar (7)

^*Incidence not available.

ACE, aphakic CE; NA, not available; PCE, pseudophakic CE.

In the present study, CE and regrafting were the 2 most common causative diseases of corneal transplantation, accounting for approximately two-thirds of all cases in our series. Several reports have indicated that the incidence of CE is on the rise in various countries, including the United States and Japan.^1,17 This trend is likely because of the increase in intraocular surgeries, such as those for cataract,¹⁸ glaucoma,¹⁹ and vitreoretinal diseases. The trend may be attributable to both evolution of safer surgical techniques and an aging population.

Regarding the causes of CE, we reported 20 years ago that postcataract surgery CE was the most common (44.4%), which was similar to the present study but accounted for somewhat fewer incidences as the cause of CE (25.1%).² Postcataract surgery CE remains a leading cause of corneal transplantation in Asian countries but not in Western countries.¹⁶ Postglaucoma surgery has seen a dramatic increase as a cause of CE in our data, increasing from 5.3% to 20.8%. Although the precise reasons for this sharp increase have not been fully explored, it likely reflects the increase in glaucoma surgeries. Iwasaki et al reported an increasing incidence of shunt tube surgery,¹⁹ a type of procedure that tends to cause more corneal endothelial damage than nonfiltering surgeries.²⁰ Higashide et al also reported accelerated endothelial cell loss following mitomycin C trabeculectomy, particularly in eyes with exfoliation syndrome and uveitic glaucoma.²¹ Price et al²² further identified preoperative glaucoma, particularly when surgically managed, as a primary risk factor for late endothelial failure following DSAEK.

Another notable change in the causative diseases for corneal transplantation is the increase in the incidence of FECD. This disease accounted for only 1.7% of CE causes in our earlier study but has risen to 10.9% in the current survey. The reasons for this increase are not entirely clear but may be partly because of improved diagnostic tools, such as the widespread use of specular microscopy. The aging of our society may also have contributed to the increase in FECD cases. Alternatively, environmental factors, such as exposure to oxidative stress, may play a role.²³ This hypothesis warrants further epidemiological investigation. Although FECD is the most common reason for corneal transplantation in the United States and Europe, it is less prevalent in other world regions. In Singapore, postcataract surgery CE, postinfectious corneal scarring, and keratoconus are the most common indications for PKP, with FECD accounting for 9%.⁶ In Australia, keratoconus and failed grafts are prevalent causes of corneal transplantation.¹⁵

In surgical procedures, we observed a dramatic increase in EK. Whereas all eyes with CE were treated with PKP in the previous national survey,² EK has now become the predominant procedure for corneal transplantation in the current study. EK was also performed in 21.2% of eyes that had previous PKP, presumably because EK has been recognized as safe procedure especially in grafted eyes without stromal opacity or high degree of astigmatism. According to the 2019 Eye Bank Association of America Statistical Report, the number of EKs performed was 1.76 times greater than that of PKP (30,650 vs. 17,409).¹³ Within EK, DSAEK was performed slightly more frequently than DMEK (117,428 and 13,215 cases, respectively), and the numbers for both methods have become similar in the most recent report.¹⁴ It is noteworthy that in the United States, 56.8% of the EKs were performed for FECD, and postcataract surgery CE accounted for only 15.5%.¹⁴ Although EK continues to evolve in Japan, DSAEK remains the standard technique, a situation similar to that in Europe.^9,10 The relatively small percentage of DMEK in our EK cases may be attributed to the lower incidence of FECD compared to Western countries. Other attributable factor for low rate of DMEK in EK may be lack of Japanese eye banking system that prepare DMEK grafts.

ALK and DALK were performed in 8.3% and 8.1%, respectively, of the corneal transplantation in this study (Fig. 2). Interestingly, more than half of the cases with dystrophy and noninfectious keratitis were treated with ALK/DALK, and approximately one-third of cases with ectatic disease, corneal scar, and infectious keratitis were treated with these techniques (Table 3). The preferred surgical procedure for ectatic diseases (mainly keratoconus) seems to differ across regions; although PKP remains the most common technique in Europe¹⁰ and the United States, a Singapore study reported better outcomes with DALK than PKP.²⁴ This discrepancy warrants further investigation. It seems that further advances in surgical techniques may enhance the adoption of these methods.

We also evaluated the short-term (1-year) graft survival rate. The overall survival rate was relatively good (80.5%). Although the survival of DALK and EK grafts was worse than that of PKP grafts performed for the same indications over the same time frame in Australia,⁴ we did not observe such a difference in our study. However, it is important to note that the preoperative conditions may vary.

In summary, this national survey on corneal transplantation in Japan indicates increases in postglaucoma CE and FECD as causative diseases. EK, particularly DSAEK, has become the leading surgical method.