Penetrating Keratoplasty: Indications and Graft Survival by Geographic Region

Abstract

Corneal transplantation, or penetrating keratoplasty (PK), is the most common form of solid-organ transplantation performed world-wide. Here, we evaluated the indications for PK and rates of transplant survival around the world by geographic region. We conducted a literature search of PubMed, MEDLINE and Google Scholar databases and identified 155 relevant studies from 41 countries published between 1987 and 2021. The most common indications for PK were keratoconus in Europe, Africa, the Middle East, Australia and New Zealand and Central and South America, bullous keratopathy in North America, and corneal scarring in Asia. The overall global mean graft survival rates at 1-, 2-, 3-, 5-, and 10-years were 88.6%, 81.2%, 78.9%, 72.8%, and 61.2%, respectively. Through this systematic analysis of PK by region, we hope to bring a new perspective to the corneal transplantation literature and to potentially highlight global differences and unmet needs in patient care.

Introduction

Penetrating keratoplasty (PK) is the full-thickness removal of the cornea and replacement by donor tissue. This surgery was first successfully performed by Zirm in 1906, in Olmutz, Czech Republic (1), and today it is the most common type of solid organ tissue transplantation performed worldwide (2, 3). Broadly speaking, PK is performed in the setting of corneal blindness, which represents a significant public health problem for the global community, (4, 5) as acquired corneal blindness is the second most common cause of visual disability worldwide (6–8). The specific indications for PK are varied and can include corneal dystrophies and degenerations, congenital opacities, bullous keratopathy (BK), trauma, keratitis, and immune rejection and/or failure of a previous corneal transplant (9).

The prevalence and causes of corneal blindness vary around the world and we know that PK outcomes, including graft survival and complication rates, can be influenced by multiple factors including indication for transplantation, preoperative comorbidities, donor tissue quality, access to cornea-trained surgeons, and follow-up care, all of which can differ by region. The purpose of the current study was to review the global corneal transplantation literature in order to examine the indications for PK and graft survival outcomes by geographic region. Individual publications can challenge the reader to extract and compare relevant information; our goal in the present report is to add to the penetrating keratoplasty literature by synthesizing this information and placing it in a global context. Thus, we have compiled a region-by-region analysis of i) the indication for PK and ii) graft survival rates following transplantation.

Methods

Literature Search

We performed a systematic review of published journal articles reporting on indications of PK and/or graft survival according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (10). PubMed, MEDLINE and Google Scholar databases were used to conduct a search of articles published from 1985 through December 2021. Search parameters were any field(s) containing: “keratoplasty” or “penetrating keratoplasty” or “corneal transplant” or “corneal graft” or “indication” or “graft survival.” Studies for PK indications were included if they represented peer-reviewed manuscripts that evaluated at least 35 transplants with either a clinical or histopathological diagnosis/indication for surgery. Studies for graft survival were included only if follow-up extended at least one year after time of transplantation and included two or more of the indications listed below in their cohort of PKs followed over time. A spreadsheet was used to standardize data extraction. Although studies varied significantly, common indications for PK that we evaluated included keratoconus (KCN), bullous keratopathy (combining aphakic and pseudophakic), corneal scarring/leukoma (including trachoma, burn, and trauma), herpetic keratitis, regraft, corneal dystrophy, and infectious ulcers. “Dystrophy” included Fuchs’ endothelial corneal dystrophy (FED) as well as stromal dystrophies that represented less than 1-3% of total PKs in any of the included studies. Other data collected included total number of PKs, number per indication, country, region, and period under review. Graft survival was evaluated at 1-, 2-, 3-, 5-, and 10-years post-transplantation when possible and mean survival was calculated at each time point for each geographic region, as well as for all studies. Only primary graft survival rates were included in these graft survival analyses. Additionally, studies in the following selective patient populations were excluded from these analyses: bilateral PK, pediatric PK, emergent PK, therapeutic PK, and repeat PK.

Surgical Technique

Full thickness penetrating corneal transplantation in the included studies were performed by a cornea-trained ophthalmologist. Donor corneas were prepared using vacuum or non-vacuum trephines, while trephination of recipient corneas was undertaken with vacuum trephine. The donor cornea size exceeded the recipient by 0.25-0.50 mm and was sutured to the recipient using sixteen 10-0 nylon interrupted sutures, a single 10-0 nylon running suture, or a combination of interrupted and running sutures. Most patients received a combination of subconjunctival steroid and antibiotic at the conclusion of the surgery.

Results

Literature Search

155 studies from 41 countries published between 1987 and 2021 were identified in our literature search and included in our analysis. These included 29 studies from North America, 37 studies from Europe, 36 studies from Asia, 7 from Africa, 16 from the Middle East, 11 from Australia and New Zealand, and 19 from Central and South America.

Indications for Penetrating Keratoplasty and Graft Survival by Region

North America

In more than 500,000 grafts performed in the United States (US) and Canada between 1967 and 2009, bullous keratopathy (pseudophakic bullous keratopathy (PBK) and aphakic bullous keratopathy (ABK)) was the leading indication for corneal transplantation (11–28). One study from 1991 found KCN to be the most common indication for PK (29). Two Canadian studies identified repeat corneal transplantation (30, 31) and FED (32) as the most common indications for PK. A review of the Eye Bank Association of America’s annual reports between 2005 and 2014 showed a significant shift in the indications for corneal transplantation with a steady decrease in bullous keratopathy and FED (33), and by 2014 the most common indication for PK was KCN (33).

In terms of graft survival, one single center study with nearly 2000 patients found graft survival rates at 1-, 2-, 3-, and 5-years to be 97%, 95%, 94%, and 91%, respectively (34), with a higher 5-year survival rate for patients with KCN (98%) and FED (98%) as compared to PBK (91%) and ABK (79%) (34). A cohort of consecutive PKs performed by one surgeon found survival rates of 93%, 70%, 61%, 48%, and 30% at 1-, 3-, 5-, 10-, and 15-years, respectively (14, 35). The Cornea Donor Study, which included 105 surgeons from 80 sites across the US, found graft survival rates of 86% and 77% at 5 and 10 years, respectively, but only included patients with bullous keratopathy and FED (36, 37). This is similar to another study’s reported survival rate of 90% at 5 years in a homogenous population of mostly Caucasians with KCN, PBK/ABK and FED (38). One group reported a 30% cumulative probability of developing graft failure at 20 years (39). A recent study evaluating graft survival through a large commercial insurance database found 3, 5 and 7 year graft survival rates of 78%, 76%, and 73%, respectively (40). Two and five-year graft survival in Canada was 79% and 65%, respectively (41). Compared to the survival rates of primary grafts above, second grafts showed lower survival rates with a 2- and 5-year graft survival rate of 64% and 46%, respectively (42) in one study and a 5- and 10-year graft survival rate of 53% and 41%, respectively, in another study (38).

Europe

As in the US, corneal transplantation is the most common type of transplantation surgery performed in the United Kingdom (UK). Studies from the 1980s into the early 2000s showed that the most common indications for PK were corneal ectasia, PBK/ABK, and repeat corneal transplantation (9, 43–48). Similar indications for PK were identified in Ireland (49, 50) and Denmark (51, 52). The mean overall 5-year graft survival for any indication was 82%, with survival rates of 93% and 89% for KCN and corneal dystrophies, respectively (47). The average time for graft failure was 28 months from surgery. One year graft survival in the Corneal Transplant Follow-up Study was 89% (53) and more recent data from the United Kingdom Transplant Registry found a 2-year graft survival rate of 93% in patients with PBK and FED (54). One study with a high percentage of regrafts (40%) reported a 5-year overall graft survival rate was 66% (55)

In Italy the Corneal Transplant Epidemiologic Study (CORTES) collected long-term graft survival data on thousands of PKs performed at 174 clinical centers from 2001-2004 (56). Keratoconus was the most common indication for surgery (47%), followed by regraft (14%) and PBK/ABK (14%). 1-, 2-, and 3- year graft survival was estimated to be 95%, 88% and 75%, respectively (56). Graft survival in patients with KCN showed a stable survival rate of 98% for the duration of the study, whereas for patients with other indications, the survival rate steadily decreased over time: with survival of 92%, 74%, and 52% after 1, 2, and 3 years, respectively (56). An update to CORTES showed a 5-year graft survival rate of 83% (57).

In Greece (58, 59) and Sweden (60), the most common indications for PK were BK and KCN, followed by dystrophies and repeat transplantation. Ten year graft survival in Sweden for any indication was 71%, with KCN (88%) having the highest survival rate and PBK/ABK (48%) the lowest (60). Similarly, in three French studies the most common indication for PK was bullous keratopathy followed by KCN (61–64). A different study from France found KCN to be almost three times as prevalent as bullous keratopathy as an indication for corneal transplantation (65). In Scotland, the leading indication for PK has been reported to be KCN (66).

In one of the previously mentioned French studies, graft survival rates after 1-, 2-, 5- and 10 years were 79%, 73%, 59% and 50%, respectively (62). Graft survival rates again differed significantly based on indication, with 95% survival for KCN, 57% for herpetic keratitis and 33% for pseudophakic bullous keratopathy. In another study from the Netherlands, patients undergoing PK for FED and PBK had 2- and 5- year graft survival rates of 96% and 90%, respectively (67).

Three studies from Spain between 2001 and 2018 included more than 10,000 PKs and identified KCN, bullous keratopathy, and stromal/endothelial dystrophies as the primary indications for transplantation (68–70). A study from the neighboring country of Portugal showed repeat transplantation as the primary indication for PK during a similar timespan, followed by corneal scarring, KCN, and PBK/ABK (71). The overall 1-, 3-, 5- and 10-year graft survival rates in Spain were 85%, 71%, 67% (70) and 65% (68), respectively. As expected, patients with KCN showed the best 10-year survival rate (95%), followed by endothelial and stromal dystrophies (both 55%). Patients receiving a first corneal transplant had a better 10-year survival rate (81%), then those receiving a second transplant (33%) or more than two transplants (16%) (68).

One of the earliest studies (in our period of literature review) on indications for PK in Germany showed corneal scars, KCN and bullous keratopathy as the leading three diagnoses for surgery (72). Subsequent histopathologic studies including over 4,500 corneal buttons found KCN to be the leading indication for PK, followed by corneal dystrophies, corneal scarring, and PBK/ABK (73–75). In Hungary (76), Slovenia (77), Poland (78, 79), and the Netherlands (80)the most common indications for PK were corneal scarring and PBK/ABK. Finally, a recent multinational registry study of 12,913 corneal transplants including 3,886 PKs (30%) from 10 European Union member states, the UK and Switzerland found an overall 2-year graft survival rate of 88%, with significantly different survival rates among indications: KCN (98%), FED (97%), PBK (87%), trauma (85%), repeat transplantation (84%), and infectious keratitis (74%) (81).

Asia

In a 1997 report on PK survival rates in India, 1, 2, and 5 year cumulative graft survival rates were reported to be 80%, 69%, and 47%, respectively (2). As with studies from other regions, the 5-year survival rate was highest for transplants performed for KCN (95%) and lowest for re-grafts (21%) (2). Factors associated with a higher relative risk of transplant failure included younger age at time of transplantation, lower socioeconomic status, and corneal neovascularization. Two other groups reported significantly lower graft survival rates at 1 (65-67%) and 2 (53-59%) years, potentially owing to the large number of high risk transplants performed in these studies and the quality of donor tissue (82, 83). The most common reported indications were PBK/ABK, corneal scarring and repeat transplantation (2). Subsequent studies spanning 1990-2012 from northern, (84–86) southern, (87, 88) and western (82, 89) India identified corneal scarring as the most common indication for PK followed by either infectious keratitis or PBK/ABK. In two studies from neighboring Pakistan, the most common indication for PK was also corneal scarring (90, 91), with comparable graft survival rates of 80%, 76% and 51% at 1, 2 and 5 years, respectively (91). The highest rate of graft survival was again in patients with KCN. The probability of survival at 30 months among KCN grafts was 90% as compared to 75% in non-KCN grafts (91).

In Nepal, Taiwan, China, and Vietnam, corneal scarring and infectious keratitis are leading indications for PK (92–102). One Nepalese study showed that 41% of all grafts performed were therapeutic PKs, with the majority being perforated corneal ulcers (93). In China, one study has reported overall graft survival rates of 94% and 80% at 1 and 2 years, respectively (99). This is similar to another study out of China reporting graft survival of 95%, 88%, and 76%, at 1, 2 and 3 years, respectively (103). Eyes with KCN had the highest graft survival rate (100%) whereas post-infectious corneal scars and repeat grafts had the lowest (<70%) (103). Unlike other countries in Asia, in Turkey the most common indication for PK was KCN (104, 105).

In several studies published between 1987 and 2013, bullous keratopathy has been reported to be the leading indication for PK in Japan, Singapore, Thailand, and the Philippines (106–112). Two other analyses from Japan and one from Thailand found corneal scarring to be the leading indication for PK (113–115). The overall rate of graft survival at 10 years and 12 years was 72% (106) and 60% (114), respectively. Graft survival rates again differed by indication: KCN (99-100%), herpetic keratitis (87%), corneal dystrophy (77-100%), corneal ulcer (59%), PBK/ABK (51%) and repeat graft (32-62%) (106, 114). Interestingly, graft survival rates were statistically higher in eyes that underwent PKP only versus PKP plus cataract surgery or anterior vitrectomy. Graft survival and rejection-free graft survival rates were statistically higher in first-time transplant recipients as compared to repeat transplants and in avascular recipient corneas as compared to vascularized corneas. Grafts performed for optical purposes had a graft survival rate of 87-94%, 72-76%, 63-80%, and 45-72%, 52%, and 44% at 1, 3, 5, 10, 15, and 20 years, respectively (109, 110, 115–117). Graft survival rates for therapeutic grafts were 57-78%, 44-58%, 36-60% and 16-52% at 1, 3, 5, and 10 years, respectively (109, 110, 115). Another group from Japan found a 12-year graft survival rate of 65% for the first PK, and 43% for the second PK (114).

Africa

In Africa, corneal disease is responsible for at least 25% of all blindness as compared to, for example, 2% in the UK, (118) with a high prevalence of diseases such as vitamin A deficiency, trachoma-associated corneal disease, and measles (119, 120). Between 2001-2006, post-inflammatory corneal opacification and KCN were the leading causes for PK in Ethiopia (121). In that study, two-year graft survival for any indication was 77% (121). In a more recent study from the same group, 44% of PKs transplanted between 2000-2013 in Ethiopia were performed for trachoma or leukoma, followed by KCN (14%), corneal dystrophies (14%), and PBK (9%) (122). In this study, graft survival for all indications was 89% and 80% at 1 and 2 years, respectively (122). 2-year graft survival rates for the two most common indications, leukoma (78% survival) and KCN (100% survival), were significantly different (122). In a paper from 2000 from Zimbabwe, KCN and post measles scarring were the two most common indications for PK (123). In addition, four studies spanning 1987 to 2014 (118, 124–126) found KCN to be the leading indication for PK in 50% or more cases. 1-year graft survival in one of these studies (Kenya) was 85.8% for all indications and 90% for KCN grafts (126). 1-year graft survival ranged from 65-68% for non-KCN grafts (118, 124) and 87-90% for KCN grafts (118, 124).

Middle East

In a 2004 paper, Al-Towerki et al. reviewed the indications for keratoplasty at a single center in Saudi Arabia between 1983 and 2002. They found that early in this time period, scarring was the leading indication for surgery, however this changed (presumably with improved health awareness and socioeconomic conditions) such that KCN became the leading indication for surgery in 2002; corneal scarring remained the second most common indication for surgery in 2002 (127). Studies from Saudi Arabia, Iran, Bahrain, Israel, and the Palestinian territories have identified KCN as the most common indication for corneal transplant in the Middle East between 1996-2019 (127–140), with a dramatic increase in the number of transplants performed for KCN from the early 1980s to the early 2000s (approximately 400% increase) (127). Genetic and environmental factors have been implicated as contributing factors to the high KCN prevalence in the Middle East (141, 142). One recent study from a specific region in Iran with a high percentage of farmers and an increased prevalence of infectious keratitis found corneal scarring to be the most common indication for PK (143).

Graft survival probabilities for any indication in Saudi Arabia have been reported to be 97%, 90%, 86-91%, and 81-84% at 1, 2, 3, and 5 years, respectively (128, 129). The overall graft survival time was 89 months (129). Similar graft survival rates were seen in a study from Israel (2008-2015), which reported 94%, 90%, 88%, and 81% survival at 1, 2, 3, and 5 years, respectively (144). One group found a 2-year graft survival rate of 96% for grafts performed for KCN and 49% for all other indications (140). As has been seen in other regions, one of the most important variables affecting graft survival is the indication for transplantation. In these studies, compared with keratoconus, there was a significantly higher risk of graft failure in eyes that underwent PK for corneal edema, stromal scarring or stromal dystrophies. The overall survival rate for a second PK performed after graft failure was 98%, 83%, and 49%, at 1, 2, and 5 years, respectively (145).

Australia and New Zealand

The Australian Corneal Graft Registry and the New Zealand Eye Bank (NZNEB) were established in 1985 and 1991, respectively. The Australian registry collects data on over 75% of all corneal grafts performed in the country (146) and the NZNEB provides donor tissue for more than 85% of all transplants performed and maintains a comprehensive prospective database (147). These two resources have been instrumental in facilitating both patient care and data analysis, and have identified KCN, followed by PBK/ABK, as the leading indications for PK in most studies over the past 35 years in this region (147–154). Two studies from 1989 (155) and 2007 (156), found herpetic keratitis and previous graft failure as the most common indications for PK, respectively. Using the Australian Corneal Graft Registry, Williams et al. reported that the 1-, 3-, 5-, 10- and 15-year graft survival rates for any indication were between 86-91%, 79%, 72-73%, 60-62%, and 46-55%, respectively (149, 150, 157, 158) The 2004 Australian Corneal Graft Registry report from the same group noted a 1-year graft survival rate of 85% in keratoplasties combined with IOL insertion or exchange, and 90% for keratoplasty alone (159). A comparable 1-year survival rate (94%) for either PK alone or in combination with cataract extraction was found by another group (156). In another study, 3-year graft survival for KCN, FED, and PBK/ABK was 96%, 93% and 76%, respectively (160). Indications for grafting other than keratoconus and corneal dystrophy as well as a history of a previously failed graft were noted to be statistically significant predictors of graft failure (152). Anterior segment inflammation, corneal vascularization, elevated IOP, aphakia or the presence of an anterior chamber intraocular lens, as well as grafts smaller than 7.0 mm or larger than 7.9 mm were all associated with subsequent corneal graft failure (149). In New Zealand, a 2011 study found the 1-year graft survival rate for all indications to be 87% and differed by indication: KCN or FED (95% survival), trauma (77%), and infection (70%) (153).

Central and South America

In 2017, 15,242 PKs were performed in Brazil, with the most transplants performed in the state of São Paulo (4,462) (161, 162). Several studies on PKs performed in Brazil and Colombia between 1988 and 2011 identified KCN as the leading indication for transplantation (161, 163–171). In contrast, two Brazilian studies along with three from Colombia found PBK/ABK to be the most common indication for PK (172–176). Two studies, one from Minas Gerais (177) and another from the Pernambuco region of Brazil (178) found ulcerative keratitis to be most prevalent diagnosis in patients undergoing PK. In the study from Pernambuco, the authors hypothesized that this may be attributable to the higher incidence of corneal ulcers in the region, an agricultural lifestyle, as well as other socioeconomic factors. Another common indication for corneal transplantation in Brazil was corneal scarring/leukoma (22% in Pará, Brazil, 33% in Pernambuco Brazil, and 23% in São Paulo) (179–181). Graft survival in Central and South America has been reported by only one group in Colombia (171). In this study, the percentage of transparent grafts at 1, 2 and 5 years was 83%, 81%, and 80%, respectively (171).

Discussion

In the present review we report global indications and graft survival rates for PK that were published in the peer-reviewed literature between 1987-2021. This study builds on a previous comprehensive systematic review on the changing indications of PK (182) and to our knowledge is the first report to compile graft survival rates over several decades and to compare this data across geographic regions. Rates of corneal blindness vary worldwide, with the prevalence of corneal disease, type of pathology and transplantation outcomes influenced by each country and region’s unique circumstances, particularly with respect to healthcare infrastructure, socioeconomic status and environmental and geographic factors (32, 174, 183). While no single report can untangle these complex variables, here we have performed a comprehensive review of indications for and outcomes of corneal transplantation to evaluate differences and also, potentially, unmet needs across different geographic regions.

Overall, the most common indication for PK worldwide was KCN. In relatively higher-income countries, the leading indications for PK tended to be KCN (73, 147), PBK/ABK (19), and a previous failed graft (9, 184). Studies from the US and Canada have documented PBK/ABK to be the leading indication of PK (19%-43% of cases) (19, 21, 32, 38) whereas some European countries and Australia have KCN as their most common indication (29%-48%) (47, 60, 65, 147, 152). Rates of KCN may be declining secondary to the introduction and widespread implementation of crosslinking in developed counties. FED was not found to be a leading cause of PK in most countries, likely owing to the introduction of endothelial keratoplasty in the early 2000s, first with Descemet’s stripping automated endothelial keratoplasty (DSAEK) and more recently with Descemet’s membrane endothelial keratoplasty (DMEK). As endothelial keratoplasty becomes more popular and available worldwide, we will likely see a further decline in PK for pathologies that primarily affect the posterior layers of the cornea such as PBK/ABK and FED.

In the Middle East and Africa, KCN was the leading indication for PK. In both regions, high rates of KCN were seen and may be attributed to the hot and arid climate, a higher rate of vernal keratoconjunctivitis (185–187) and atopic disease (188), and specifically in the Middle East, a higher prevalence of KCN due to genetic predisposition. Additionally, the ubiquitous burden of ocular disease in desert climates (189, 190) may contribute to contact lens intolerance, thus increasing the rate of PK for KCN. In Asia, corneal scarring tended to be the leading indication for PK with rates ranging from 14% to 61% (2, 95, 123). Endemic trachoma and cases of resolved infectious keratitis are possible causes of nonspecific corneal scars and opacities in these countries. It is also possible that pathologies with a higher degree of urgency and associated co-morbidities (such as infectious keratitis) may receive preferential surgical treatment over other non-urgent etiologies, such as KCN, due to donor tissue availability in these regions (98, 139). As a comparison, in other regions we found that corneal scarring was responsible for approximately 7% of PKs in the US, 6% in the UK, and 8% in France, compared with 40% in India, 32% in Nepal, and 26% in China.

Based on the data in the articles reviewed, we determined overall global mean graft survival rates at 1, 2, 3, 5, and 10 years to be 88.6%, 81.2%, 78.9%, 72.8%, and 61.2%, respectively. Although these numbers are derived from a heterogenous mix of individual studies, some broad conclusions can still be made. The highest 1-year graft survival rates were reported in North America, the Middle East, and Australia. In addition, keratoconus and FED were identified as the preoperative diagnoses associated with the best overall graft survival rate at various time points in multiple studies. In contrast, noninfectious keratitis, bullous keratopathy, and trauma were all found to have consistently lower rates of graft survival (2, 60, 150, 191).

Primary graft survival in North America ranged from 60-98% at 5 years, with the indication for surgery contributing to this large range of success. In Europe, graft survival rates ranged from 59-90% at 5 years and similarly varied predominantly based on surgical indication and percentage of high-risk grafts. The higher overall rates of graft survival seen in the Middle East and Australia may be due in part to KCN being the leading indication for PK in these regions, with approximately 40% and 33% of grafts being performed for KCN, in the Middle East and Australia, respectively. The lowest overall 1-year graft survival rates were seen in Asia (86.4%) and South America (83%). Five-year graft survival rates in Asia were 47-67%; this lower rate of success compared to the US and Europe may be accounted for by the higher rate of infectious keratitis and corneal ulcer as indications for surgery, which are known to correlate with higher graft failure rates.

Corneal blindness is the second most common cause of vision impairment worldwide and disproportionately affects economically developing countries (6–8). Over the past forty years, multiple innovations have led to progress in addressing corneal blindness, including the implementation of preventive and ameliorative treatments for trachoma, vitamin A supplementation, and improved nutrition and public sanitation, among others (192). However, there still exists an imbalance between corneal blindness and access to corneal transplantation, with an overall ratio of patients undergoing PK to those waiting for PK of 1:70 (3). More than 50% of the world’s population has no access to corneal transplantation, (3) and the areas with the greatest need for this procedure often also have the fewest resources available, such as eye banks, adequate surgical facilities and sub-specialty-trained surgeons (193). By reporting the indications for PK and graft survival outcomes by geographic region, it is our goal to bring a new perspective to the corneal transplantation literature and highlight differences and potential disparities throughout the world. We hope that this can contribute to the identification of unmet needs with respect to corneal blindness and transplantation, and also encourage the global community to undertake initiatives and expand modern practices to improve quality of care for all.

Table 1.

Indications for Penetrating Keratoplasty per Geographic Region and Country

Indications (%)	KCN	PBK/ABK	Scarring	Herpetic	Regraft	Dystrophy†	Infectious*	Number of PKs	Study Period	Reference
NORTH AMERICA
Canada	16	19	3	6	18	10	3	6222	1964-1997	Maeno et al (27)
Canada	17	22	14	9	12	8		659	1978-1987	Damji et al (26)
Canada	12	38		19				539	1982-1990	Boisjoly et al (24)
Canada	10	35	3	4	22	8	4	904	1986-1995	Liu et al (25)
Canada	11	52		7		14	5	696	1986-1993	Sit et al (41)
Canada	17	20	14	4	21	10	4	4156	1995-2005	Sheldon et al (31)
Canada	12	26			27	13	4	794	1996-2004	Dorrepaal et al (30)
Canada	14	30	1	4	22	18	3	7100	2000-2009	Boimer et al (28)
Canada	16	17	13	3	17	19	5	4843	2002-2011	Tan et al (32)
United States	21	36		3		27		500	1976-1986	Ing et al (14)
United States	19	25	11		13	14		502	1978-1986	Foulks (11)
United States	24	21	14	5	8	13		1594	1980-1988	Lindquist et al (29)
United States	15	20			11	14		>500000	1980-2004	Darlington et al (22)
United States	24	28	8	3	13	8	6	999	1981-1990	Mamalis et al (15)
United States	10	51	6	1	7	20		1819	1982-1990	Price et al (34)
United States	11	40	11		9	23		4217	1982-1996	Dobbins et al (19)
United States	15	37	2	4	10	18	3	2299	1983-1988	Brady et al (13)
United States	7	37	14	5	18	5	3	1019	1984-1988	Mohamadi (12)
United States	13	33	12		17	13		3941	1985-1988	Hyman et al (16)
United States	7	31	11		21		6	1104	1989-1993	Flowers et al (17)
United States	13	34	2	4	18	18	3	2442	1989-1995	Lois et al (18)
United States	13	25	1	1	12	13	5	30962	1990-2000	Sugar et al (20)
United States	15	27	8	1	18	16	3	1529	1996-2000	Cosar et al (21)
United States	16	28	5	3	22	12	4	1162	2001-2005	Ghosheh et al (23)
United States	21	13			16	7	3	275698	2005-2014	Park et al (33)
EUROPE
Denmark	7	38		14	11	14		180	1984-1993	Haamann et al (51)
Denmark	18	24		6		37		63	1995-2001	Jacobsen et al (52)
France	29	10	7	11	10	9		3736	1980-1999	Legeais et al (65)
France	20	28	9	19	10			103	1981-1988	Muraine et al (62)
France	13	28	8	7	11	8		1540	1982-2000	Leger et al (61)
France	18	41	11		10	14		1209	1992-2010	Guilbert et al (63)
France	19	24			14	15		34187	2004-2015	Ricouard et al (64)
Germany	21	17	20		16	17	5	1250	1992-1996	Cursiefen et al (73)
Germany	26	15	14	13	7	21		1200	2001-2010	Wang et al (74)
Germany	22	11	17		17	9	18	2123	2011-2018	Pluzsik et al (75)
Greece	26	29	8	5	12	5	8	2233	1982-2006	Siganos et al (58)
Greece	10	38	12		18	11	6	960	1999-2015	Droutsas et al (59)
Hungary	19	12	28	5	19	6	1	4778	1946-2009	Modis et al (76)
Ireland	34	8		26		16		133	1975-77, 85-86	Collum et al (49)
Ireland	45	23	16		9	5		37	2001-2005	Guerin et al (50)
Italy	47	14		6	14			4415	2001-2004	Fasolo et al (56)
Netherlands	25	28	5	14		7		2156	1991-1992	Beekhuis et al (80)
Poland	13	22	24	9	11	13		1375	1988-2014	Jankowska-Szmul et al (78)
Poland	18	25	15		8	11		517	2000-2004	Wylegala et al (79)
Portugal	13	12	14		37			506	2011-2016	Bernardes et al (71)
Scotland	29	10			19	14		921	2001-2010	Ting et al (66)
Slovenia	21	23	21		9	15		290	1985-2004	Pahor et al (77)
Spain	38		8			25	20	895	2001-2006	Barraquer et al (68)
Spain	12	32	10	3		24		432	2001-2017	Montesel et al (70)
Spain	11	21	5		14	18	8	9457	2011-2018	Sabater-Cruz et al (69)
Sweden	29	21			3	18		1957	1997-2000	Claesson et al (60)
UK	20	5	9	19	16	12	2	96	1981-1986	Claoue et al (44)
UK	50	3		41	16	25		175	1980-1988	Kervick et al (43)
UK	17	8	5	12	41	9		3555	1971-1990	Sharif et al (45)
UK	20	25		11		18		4560	1987-1991	Vail et al (46)
UK	15	8		6	41	13		1096	1990-1999	Al-Yousuf et al (9)
UK	24	22		9	20	14	5	203	2000-2003	Rahman et al (47)
UK	21	34			15		7	17400	1999-2009	Keenan et al (48)
ASIA
China	6	12	36	19	11	4	12	229	1994-2003	Zhang et al (96)
China	11	9	14	15	6	2	28	3758	1996-2007	Xie et al (97)
China	14	11	27	24	3	9	12	203	1999-2009	Pan et al (99)
China	11	9	5	19	7	3	37	875	2005-2010	Wang et al (98)
China	12	9	3	15	12	5	39	1405	2010-2017	Sun et al (101)
China	5	3	25	5	7	9	25	19896	2014-2018	Gao et al (100)
India	7	25	23		20	10		1725	1987-1995	Dandona et al (2)
India	10	30	31		12	13		1927	1990-2000	Sangwan et al (87)
India		15	38		11	4	28	2022	1997-2003	Sony et al (84)
India	5	30	56	3	14	3		181	2005-2007	Joshi et al (82)
India	5	9	61		13		3	102	2002-2012	Dasar et al (88)
India	4	20	40		8		23	311	2006-2008	Kumari et al (89)
India	1	27	33		12	3	21	145	2012-2014	Raj et al (85)
India	1	10	42		9		16	102	2015-2017	Singh et al (86)
Japan	28	11	38		14	6		698	1971-1992	Yamagami et al (113)
Japan	21	24	2	12	17	7	18	396	1987-1997	Inoue et al (106)
Japan	7	27	42		16		5	509	1998-2014	Ono et al (114)
Japan	14	37	25		6	2	6	319	2003-2018	Nishino et al (107)
Nepal	4	9	37				35	472	1994-1995	Tabin et al (92)
Nepal	7	9	27		11	2	41	645	2005-2010	Bajrachharya et al (93)
Nepal	3	3	31		14		44	36	2014-2015	Singh et al (94)
Pakistan	17	6	50		13	6	7	672	1998-2010	Chaudhry et al (90)
Pakistan	17	8	37		13	10		437	2005-2014	Chaudhry et al (91)
Philippines	2	25	24	4	10	8	18	2131	1996-2004	Padilla et al (112)
Singapore	10	26	10		12	10		327	1991-1995	Wong et al (108)
Singapore	10	23	20		12			1130	1991-2006	Tan et al (109)
Singapore	12	35	16			14		1050	1991-2010	Anshu et al (110)
Taiwan	3	17	28		21	5	18	770	1987-1999	Chen et al (95)
Thailand		29	22		9	20	18	45	1996-1999	Chaidaroon et al (111)
Thailand	4	16	25		14	25	9	704	2000-2013	Reinparyoon et al (115)
Turkey	34	14	20	12	6	12		1330	1995-2014	Altay et al (105)
Turkey	28	23	19		13	12		815	2004-2014	Bozkurt et al (104)
Vietnam	2	5	24		8	10	48	1390	2002-2014	Dong et al (102)
AFRICA
Ethiopia	14	9	44		6	14	3	321	2000-2013	Ayalew et al (122)
Ethiopia	23		48					111	2001-2006	Tilahun et al (121)
Kenya	50		11	8	7	7		216	1987-1993	Yorston et al (118)
Kenya	49	18						174	2001-2011	Hydara et al (124)
Kenya	66		22					118	2012-2014	Chen et al (126)
South Africa	64	6			3	10		104	2011-2014	Khan et al (125)
Zimbabwe	27	13	29	11					1992-1998	Mkanganwi et al (123)
MIDDLE EAST
Bahrain	33	13	27	4	7	3	6	298	1996-2015	Al-Yousuf et al (135)
Iran	40	19	16		8	5	5	66539	1991-2017	Javadi et al (134)
Iran	35	15	19		5	6		19668	1994-2004	Kanavi et al (132)
Iran	38	12	13	4	11	1	10	1859	2004-2009	Zare et al (133)
Iran	3	29	30		12		21	115	2017-2019	Eidizadeh et al
Israel	22	7	7	9	11		7	1018	1961-1990	Frucht-Pery et al (136)
Israel	28	8	7	7	13		7	1681	1961-2000	Yahalom et al (138)
Israel	51	17			20	22		154	2001-2002	Claesson et al (137)
Palestinian territories	38	2	17	11	7	6	14	416	1988-1992	De Cock et al (139)
Palestinian territories	49							161	2001-2002	Claesson et al (140)
Saudi Arabia	40	8	20		11	7	10	8318	1983-2002	Al-Towerki et al (127)
Saudi Arabia	51		19			9		910	1997-2001	Wagoner et al (128)
Saudi Arabia	39	13	18		12	18		85	2000-2008	Omar et al (129)
Saudi Arabia	50	13			9	16	3	244	2005-2010	Arfaj et al (130)
Saudi Arabia	53	14	11		9	7	2	570	2008-2013	Al-Arfai et al (131)
AUSTRALIA AND NEW ZEALAND
Australia	37	8	2	12	16	3	4	511	1982-1986	Brooks et al (148)
Australia	33	23	12	3	13	6	3	1483	1985-1989	Williams et al (157)
Australia	30	25	11		18	7		4499	1985-1995	Williams et al (158)
Australia	32	26	7	1	20	7	3	18686	1985-2007	Williams et al (150)
Australia	30	23	2	4	21	11	2	17301	1985-2012	Keane et al (151)
Australia	22	21		26	16	3		37	1987-1988	Collie et al (155)
Australia	20	8	13		22	21		107	2001-2003	Green et al (156)
New Zealand	45	18	6	7	9	8	3	1308	1991-1999	Edwards et al (147)
New Zealand	45	17	5	7	7	9	3	1820	1994-2003	Patel et al (153)
New Zealand	41	14		4	17	11	3	2205	2000-2009	Cunningham et al (154)
CENTRAL AND SOUTH AMERICA
Brazil	29	21	13	3	11	4	4	507	1988-1997	Cattani et al (165)
Brazil	35	26					10	91	1990-1998	Fabris et al (164)
Brazil	22	10		4	17	9	1	249	1991-1995	Nishiwaki-Dantas (163)
Brazil	17	13	4	5	15	8	12	836	1991-2005	Sano et al (168)
Brazil	9	42		7	4	9	6	85	1995-1997	Florence et al (172)
Brazil	19	20	18				21	814	1998-2002	Amaral et al (178)
Brazil	24	23	7		6	12	11	205	1999-2000	Endriss et al (166)
Brazil	50	8	3		10	7	17	857	1999-2003	Flores et al (161)
Brazil	16	16	14		8	3	35	887	1999-2005	Neves et al (177)
Brazil	14	39	23		8		6	320	2000-2002	Araujo et al (173)
Brazil	16	19	23	5	13	3	7	1085	2000-2009	Barbosa et al (180)
Brazil	7	28	29		13	3	15	1261	2001-2009	Almeida Sobrinho et al (179)
Brazil	65	21	11			3		171	2003-2003	Calix Netto et al (167)
Brazil	51	6	4	13	15	5	3	100	2006-2011	Zeschau et al (169)
Brazil	22	18	33		10	16		871	2011-2012	Almeida et al (181)
Colombia	13	35	16		8	8	14	403	2004-2011	Galvis et al (174)
Colombia	37	17	21		12			712	2010-2017	Mora et al (171)
Colombia	16	30		21	7	9	9	1104	2012-2014	Gonzalez Perez et al (175)
Colombia	5	46				9	22	346	2012-2016	Galvis et al (176)

Abbreviations: Keratoconus, KCN, pseudophakic bullous keratopathy/aphakic bullous keratopathy, PBK/ABK, penetrating keratoplasty, PK

^†Including stromal and endothelial dystrophy (and Fuchs endothelial dystrophy)

^*Non-herpetic

Table 2.

Graft Survival Rate at 1-, 2-, 3-, 5-, and 10-year After Penetrating Keratoplasty per Geographic Region^†

Graft Survival Rate	Year After Transplant					Reference
	1	2	3	5	10
Global Average	88.6	81.2	78.9	72.8	61.2
NORTH AMERICA
Canada		79		65		Sit et al (41)
United States	97	95	94	91		Price et al (34)
United States			78	76		Ahmad et al (40)
United States				86	77	Dunn et al (37)
United States				90	82	Thompson et al (38)
United States	93		70	61	48	Ing et al (14)
United States	92		70	60	46	Patel et al (35)
Regional Average	94	87	78	76	63
EUROPE
Europe		88				Dunker et al (81)
France	79	73		59	50	Muraine et al (62)
Italy	95	88	75			Fasolo et al (56)
Italy				83		Fasolo et al (57)
Netherlands		96		90		Dickman et al (67)
Spain					65	Barraquer et al (68)
Spain	85		71	67		Montesel et al (70)
Sweden					71	Claesson et al (140)
UK	89					Vail et al (53)
UK				82		Rahman et al (47)
UK		93				Figueiredo et al (54)
UK	90		81	66		Beckingsale et al (55)
Regional Average	88	88	76	75	62
ASIA
China	94	80				Pan et al (99)
China	95	88	76			Li et al (103)
India	80	69		47		Dandona et al (2)
India	65	53				Joshi et al (82)
India	67	59				Arya et al (83)
Japan					72	Inoue et al (106)
Pakistan	80	76		51		Chaudhary et al (91)
Singapore	87		72	64	52	Tan et al (109)
Singapore				67		Ang et al (116)
Singapore	91			67	55	Anshu et al (110)
Singapore	94			80	72	Arundhati et al (117)
Thailand	92		76	63	45	Reinprayoon et al (115)
Regional Average	85	71	75	63	59
AFRICA
Ethiopia	89	80				Ayalew et al (122)
Ethiopia		77				Tilahun et al (121)
Kenya	86					Chen et al (126)
Kenya		82				Hydara et al (124)
Kenya		65				Yorston et al (118)
Regional Average	88	76
MIDDLE EAST
Israel	94	90	88	81		Sternfeld et al (144)
Saudi Arabia	97	90	86	81		Wagoner et al (128)
Saudi Arabia			91	84		Omar et al (129)
Regional Average	96	90	88	82
AUSTRALIA
Australia		81		65		Bishop et al (194)
Australia	91		79			Williams et al (157)
Australia	91		79	72		Williams et al (158)
Australia	86			73	62	Williams et al (149)
Australia	87			73	60	Williams et al (150)
Australia	94					Green et al (156)g
New Zealand	87					Patel et al (153)
Regional Average	89	81	79	71	61
CENTRAL AND SOUTH AMERICA
Colombia	83	81		80		Mora et al (171)

^†Graft survival rates included are for primary grafts only