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. 2020 Oct 15;15(10):e0239939. doi: 10.1371/journal.pone.0239939

Survey report on keratoplasty in China: A 5-year review from 2014 to 2018

Hua Gao 1,2, Ting Huang 2,3, Zhiqiang Pan 2,4, Jie Wu 2,5, Jianjiang Xu 2,6, Jing Hong 2,7, Wei Chen 2,8, Huping Wu 9, Qian Kang 10, Lei Zhu 2,11, Lingling Fu 12, Liqiang Wang 2,13, Guigang Li 2,14, Zhihong Deng 15, Hong Zhang 2,16, Hui Xu 17, Qingliang Zhao 18, Hongshan Liu 19, Linnong Wang 2,20, Baihua Chen 2,21, Xiuming Jin 2,22, Minghai Huang 23, Jizhong Yang 24, Minghong Gao 2,25, Wentian Zhou 26, Hanping Xie 2,27, Yao Fu 2,28, Feng Wen 29, Changbo Fu 30, Shaozhen Zhao 2,31, Yanning Yang 2,32, Yanjiang Fu 33, Tao Yao 34, Chaoqing Wang 35, Xiaonan Sun 36, Xiaowei Gao 2,37, Maimaitiming Reziwan 38, Yingping Deng 2,39, Jian Li 40, Limei Liu 41, Bo Zeng 42, Lianyun Bao 43, Hua Wang 2,44, Lijun Zhang 2,45, Zhiyuan Li 46, Zhijian Yin 47, Yuechun Wen 48, Xiao Zheng 49, Liqun Du 50, Zhenping Huang 51, Xunlun Sheng 52, Hui Zhang 2,53, Lizhong Chen 54, Xiaoming Yan 2,55, Xiaowei Liu 56, Wenhui Liu 57, Yuan Liu 58, Liang Liang 59, Pengcheng Wu 60, Lijun Qu 61, Jinkui Cheng 62, Hua Zhang 63, Qige Qi 64, Yangkyi Tseten 65, Jianping Ji 3, Jin Yuan 2,3, Ying Jie 4, Jun Xiang 6, Yifei Huang 2,13, Yuli Yang 2,27, Ying Li 2,56, Yiyi Hou 1, Tong Liu 1, Lixin Xie 2,66,*,#, Weiyun Shi 1,2,*,#
Editor: Yu-Chi Liu67
PMCID: PMC7561196  PMID: 33057425

Abstract

To provide the general information on corneal transplantation (CT) in China, China Cornea Society designed a questionnaire on CT from 2014 to 2018 and entrusted it to 31 committee members for implementation of the survey nationwide. This article presents the results of the survey and compares the indicators used in the survey and those in the annual statistical report released by the Eye Bank Association of America (EBAA). The number of corneal transplantations completed by the 64 hospitals from 2014 to 2018 was respectively 5377, 6394, 7595, 8270 and 8980, totally 36,616 (22,959 male and 13,657 female). The five largest hospitals by the number of corneal transplantations completed 15,994 surgeries in total, accounting for 43.68% of all the surgeries performed in the 64 hospitals. The most common indication for corneal transplantations was corneal leukoma (7683, 20.98%), followed by bacterial keratitis (4209, 11.49%), corneal dystrophies (4189, 11.44%), keratoconus (3578, 9.77%) and corneal perforation (2839, 7.75%). The main surgical techniques were penetrating keratoplasty (PK) (19,896, 54.34%), anterior lamellar keratoplasty (ALK) (13,869, 37.88%). The proportion of PK decreased from 57.97% in 2014 to 52.88% in 2018 while the proportion of ALK increased from 36.04% in 2014 to 37.92% in 2018. The geographical distribution of keratoplasties performed in China is unbalanced. PK and ALK were the main techniques of CT and corneal leukoma, bacterial keratitis and corneal dystrophies were the main indications for CT in China.

Introduction

According to the World Health Organization, corneal diseases are one of the leading causes of blindness globally [1]. Approximately 180,000 cases of corneal transplantations are performed worldwide each year [2], of which 40,000 to 50,000 cases are in the United States, restoring vision for patients with corneal blindness [3,4]. China is the largest and most populous developing country in the world and corneal diseases are the second leading causes of blindness [57]. According to the multi-center study on infectious keratitis in China conducted by Song et al. in 2010, the number of people with corneal blindness in at least one eye in China was estimated to be about 3 million at that time [8].

Eye Bank Association of America (EBAA) is the only accredited organization in America that distributes donated eye tissues and collects information on the utilization of the tissues in all its member banks. Two articles based on the statistical reports of EBAA has been published, reporting the trends of penetrating keratoplasty (PK) from 1980 to 2004 and the condition of keratoplasty in the United States from 2005 through 2014 respectively [3,4]. All these data can provide information for ophthalmologists to understand the general situation of corneal transplantation (CT), and play a positive role in promoting the development of CT and the improvement in surgical techniques.

Although several single center based articles about keratoplasties have been published these years [914], currently, there is no national eye bank association or eye bank union in China, therefore, no exact data is available for the total number of corneal transplantations each year, the main indications for CT, surgical techniques of CT, etcetera, which limits the formulation and implementation of corneal blindness-related policies and then the process of restoring vision for the blind in China. To get an overview of keratoplasties in China, the Corneal Disease Group of Ophthalmological Society of Chinese Medical Association (China Cornea Society) designed a questionnaire on CT (S1 Table) and entrusted the questionnaire to its 31 committee members for the implementation of the survey in hospitals. 64 hospitals participated in the survey and returned the questionnaire. The results of the survey show that there are many differences in surgical techniques of CT, indications, and other aspects between China and America. The survey data are now available for reference.

Materials and methods

The China Cornea Society entrusted the questionnaire to its 31 committee members for the implementation of the survey in China. A total number of 64 hospitals were involved in the survey and asked to fill in the questionnaires. This study was approved by the Institutional Review Board of Shandong Eye Institute and adhered to the tenets of the Declaration of Helsinki.

Indicators of the survey included the number of keratoplasties performed between January 2014 to December 2018, general conditions of each patient, geographical distribution of surgeries, indications for surgeries, surgical techniques. Detailed data of each case was collected.

Indications for corneal transplantation

Indications for CT mainly include 1) fungal keratitis, 2) bacterial keratitis, 3) herpes simplex virus keratitis, 4) Acanthamoeba keratitis), 5) corneal dystrophies (granular dystrophy, lattice dystrophy, macular dystrophy, Fuchs’ dystrophy, and other dystrophies), 6) trauma (acid burns, alkali burns, thermal burns, and other burns), 7) immune-related keratitis (Mooren's Ulcer, rheumatoid arthritis-associated peripheral ulcerative keratitis, and Stevens–Johnson syndrome), 8) corneal degeneration, 9) keratoconus, 10) pseudophakic bullous keratopathy (PBK), 11) corneal tumor, 12) corneal leukoma, 13) corneal perforation, 14) corneal staphyloma, 15) exposure keratitis, 16) pterygium-related corneal opacity, and 17) graft opacity.

Corneal transplantation techniques

Corneal transplantation techniques mainly include 1) PK, 2) lamellar keratoplasty (LK), in the form of anterior lamellar keratoplasty (ALK) and endothelial keratoplasty (EK), 3) keratoprosthesis, and 4) keratolimbal allograft.

Statistical method

The data were analyzed using SPSS Statistics version 25 (IBM, Armonk, NY). P values less than 0.05 were regarded as statistically significant.

Results

64 tertiary hospitals in China returned the questionnaires. According to the detailed information the hospitals provided, the number of CT performed in the five years was 5377, 6394, 7595, 8270, and 8980 respectively, totally 36,616.

Number of corneal transplantations in hospitals and geographical distribution

The five largest hospitals by number of corneal transplantations performed from 2014 through 2018 are Shandong Eye Institute (including Eye Hospital of Shandong First Medical University and Qingdao Eye Hospital of Shandong First Medical Univeristy) (4001), Zhongshan Ophthalmic Center (3837), Beijing Tongren Hospital (3079), No. 1 Hospital of Xi’an City (2569), Eye and Ear, Nose, Throat Hospital of Fudan University (2508) and totally conducted 15,994 keratoplasties, accounting for 43.68% of the totally reported keratoplasties (Fig 1).

Fig 1. Number of corneal transplants performed in each involved hospital.

Fig 1

1: Shandong Eye Institute 2: Zhongshan Ophthalmic Centre, Sun Yat-sen University 3: Beijing Tongren Hospital, Capital Medical University 4: No.1 Hospital of Xi’an City 5: Eye and Ear, Nose, Throat Hospital, Fudan University 6: Peking University Third Hospital 7: Eye Hospital of Wenzhou Medical University 8: Affiliated Xiamen Eye Center of Xiamen University 9: Chengdu AiDi Eye Hospital 10: Henan Eye Institute, Henan Eye Hospital 11: Hefei Puri Ophthalmological Hospital 12: Chinese PLA General Hospital, Medical School of Chinese PLA 13: TongJi Hospital, Tongji Medical College, Huazhong University of Science and Technology 14: The Third Xiangya Hospital of Center South University 15: The First Affiliated Hospital of Harbin Medical University 16: The First Hospital of Jilin University 17: Suzhou Lixiang Eye Hospital 18: Henan Eye Institute, Henan Eye Hospital 19: Nanjing First Hospital, Nanjing Medical University 20: Department of Ophthalmology, Second Xiangya Hospital, Central South University 21: Affiliated Second Hospital, School of Medicine, Zhejiang University 22: Nanjing Aier Eye Hospital 23: Shanxi Eye Hospital 24: General Hospital of Northern Theater Command Hospital 25: Affiliated Eye Hospital of Nanchang University 26: The First Hospital Affiliated to Army Medical University 27: Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine 28: Ningbo Eye Hospital 29: Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University 30: Tianjin Medical University Eye Hospital 31: Renmin Hospital of Wuhan University 32: Daqing Ophthalmologic Hospital 33: Shenyang He Eye Hospital 34: Jinan Mingshui Eye Hospital 35: The 4th People's Hospital of Shenyang 36: 474 Hospital of PLA 37: Urumqi City Ophthalmology and Otolaryngology Hospital 38: West China Hospital of Sichuan University 39: The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital 40: Weifang Eye Hospital 41: General Hospital of the Central Theater of the Chinese People’s Liberation Army, Wuhan, Hubei Province 42: Nanjing Ningyi Eye Center 43: Department of Ophthalmology, Xiangya Hospital, Central South University 44: The People’s Third Hospital of Dalian, Dalian Medical University, The third People's Hospital of Dalian 45: The People's No.1 Hospital of Chenzhou 46: The First Affiliated Hospital of Dali University 47: The First Affiliated Hospital of University of Science and Technology of China, Anhui Provincial Hospital 48: The Army Characteristic Medical Center 49: Qilu Hospital of Shandong University 50: Jinling Hospital, Nanjing University School of Medicine 51: Ningxia Eye Hospital, The People’s Hospital of Ningxia Hui Autonomous Region 52: First Affiliated Hospital of Kunming Medical University 53: Lunan Eye Hospital 54: Peking University First Hospital 55: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College 56: Wuxi Second People's Hospital 57: Guizhou Jinglang Eye Hospital 58: Yichang Central People's Hospital 59: Lanzhou University Second Hospital 60: The Second Affiliated Hospital of Harbin Medical University 61: Jingzhou First People's Hospital 62: Shijiazhuang No.1 Hospital 63: Hulunbuir People's Hospital 64: Tibetan Traditional Tibet Medical Hospital of Tibet Autonomous Region.

According to the location of the hospitals reported, 30 provincial-level administrative units were included. The total number of CT performed in the five years in each administrative unit is as follows (Table 1).

Table 1. Total number of CT performed in the five years in each provincial-level administrative unit.

Number* %
Provincial-level administrative unit Beijing 6077 16.60
Shandong 4427 12.09
Guangdong 3976 10.86
Shanghai 2791 7.62
Zhejiang 2 640 7.21
Shaanxi 2 569 7.02
Fujian 1 671 4.56
Jiangsu 1 650 4.51
Sichuan 1 540 4.21
Hunan 1 371 3.74
Henan 1 043 2.85
Hubei 985 2.69
Anhui 917 2.50
Liaoning 825 2.25%
Heilongjiang 787 2.15
Jilin 554 1.51
Hainan 505 1.38
Guangxi 392 1.07
Chongqing 384 1.05
Shanxi 379 1.04
Jiangxi 325 0.89
Xinjiang 313 0.85
Tianjin 241 0.66
Yunnan 134 0.37
Ningxia 53 0.14
Guizhou 34 0.09
Gansu 15 0.04
Hebei 8 0.02
Inner Mongolia 8 0.02
Tibet 2 0.01

* in descending order.

The five largest provincial-level administrative units by number of CT have completed 19 911 cases (54.38%), while the five smallest units have only completed 67 cases (0.18%).

Age and gender distribution of cornea transplant recipients

Among the 36,616 patients who underwent CT, 22,959 (62.70%) were male and 13,657 (37.30%) were female. The distribution of age is as follows (Table 2).

Table 2. Age distribution of cornea transplant recipients.

Age (year)
<1 1–10 11–20 21–30 31–40 41–50 51–60 61–70 71–80 >80
Number (%) 538 (1.47) 3123 (8.53) 2846 (7.77) 3607 (9.85) 3427 (9.36) 6053 (16.53) 7067 (19.30) 6438 (17.58) 2851 (7.79) 666 (1.82)

Indications for corneal transplantation

The 5 leading indications for CT in China were corneal leukoma (7683, 20.98%), bacterial keratitis (4209, 11.49%), corneal dystrophies (4189, 11.44%), keratoconus (3578, 9.77%), and corneal perforation (2839, 7.75%) (Fig 2).

Fig 2. Indications for corneal transplantation.

Fig 2

Surgical techniques

According to the data we collected, the number of PK accounts for 54.34% of all the keratoplasties performed in the five years, ALK 37.88%, EK 6.87%, keratoprosthesis 0.72%, and keratolimbal allograft 0.19% (Fig 3).

Fig 3. Tendency of preferred surgical techniques.

Fig 3

ALK = anterior lamellar keratoplasty; PK = penetrating keratoplasty; EK = endothelial keratoplasty.

The most common surgical technique was PK, although decreasing from 57.97% in 2014 to 52.88% in 2018. ALK increased from 36.04% to 37.92% in the five years (P<0.001) and EK increased from 5.52% to 7.75% (P<0.001). The indications for ALK are shown in Table 3 and the indications for PK are shown in Table 4.

Table 3. Indications for anterior lamellar keratoplasty from 2014 through 2018.

Year, Number (%)
Indication 2014 2015 2016 2017 2018
Corneal leukoma 280(14.45) 338(15.23) 387(12.86) 591(17.93) 455(13.36)
Keratoconus 255(13.16) 297(13.38) 459(15.25) 547(16.59) 531(15.59)
Corneal tumor 217(11.20) 245(11.04) 370(12.29) 468(14.19) 536(15.74)
Bacterial keratitis 223(11.51) 232(10.46) 406(13.49) 391(11.86) 458(13.45)
Corneal degeneration 164(8.46) 151(6.80) 245(8.14) 323(9.80) 296(8.69)
Corneal dystrophies 88(4.54) 158(7.12) 211(7.01) 154(4.67) 283(8.31)
Corneal perforation 126(6.50) 144(6.49) 199(6.61) 176(5.34) 167(4.90)
Immune-related keratitis 103(5.31) 161(7.26) 185(6.15) 121(3.67) 141(4.14)
Fungal keratitis 108(5.57) 49(2.21) 129(4.29) 202(6.13) 222(6.52)
Trauma 107(5.52) 129(5.81) 157(5.22) 104(3.15) 98(2.88)
Herpes simplex virus keratitis 94(4.85) 131(5.90) 122(4.05) 77(2.34) 92(2.70)
Graft opacity 32(1.65) 47(2.12) 56(1.86) 84(2.55) 85(2.50)
Pseudophakic bullous keratopathy 93(4.80) 74(3.33) 43(1.43) 9(0.27) 4(0.12)
Pterygium-related corneal opacity 16(0.83) 25(1.13) 20(0.66) 26(0.79) 19(0.56)
Acanthamoeba keratitis 23(1.19) 27(1.22) 10(0.33) 11(0.33) 10(0.29)
Corneal staphyloma 7(0.36) 8(0.36) 8(0.27) 13(0.39) 8(0.23)
Exposure keratitis 2(0.10) 3(0.14) 3(0.10) 0(0) 0(0)

Table 4. Indications for penetrating keratoplasty from 2014 through 2018.

Year, Number (%)
Indication 2014 2015 2016 2017 2018
Corneal leukoma 942(20.22) 1043(28.04) 1064(26.30) 1238(29.03) 1194(25.14)
Bacterial keratitis 289(9.27) 348(9.35) 492(12.16) 555(13.01) 710(14.95)
Corneal perforation 214(6.87) 315(8.47) 360(8.90) 518(12.15) 600(12.63)
Corneal dystrophies 285(9.14) 347(9.33) 406(10.04) 330(7.74) 449(9.45)
Fungal keratitis 257(8.25) 196(5.27) 382(9.44) 456(10.69) 466(9.81)
Keratoconus 296(9.50) 387(10.40) 342(8.45) 247(5.79) 213(4.49)
Graft opacity 208(6.67) 250(6.72) 271(6.70) 285(6.68) 313(6.59)
Corneal degeneration 142(4.56) 164(4.41) 166(4.10) 201(4.71) 276(5.81)
Herpes simplex virus keratitis 117(3.75) 107(2.88) 141(3.49) 177(4.15) 230(4.84)
Pseudophakic bullous keratopathy 145(4.65) 111(2.98) 136(3.36) 105(2.46) 136(2.86)
Trauma 71(2.28) 100(2.69) 101(2.50) 85(1.99) 85(1.79)
Corneal tumor 92(2.95) 129(3.47) 78(1.93) 30(0.71) 33(0.69)
Immune-related keratitis 39(1.25) 65(1.75) 65(1.68) 24(0.56) 28(0.59)
Pterygium-related corneal opacity 1(0.03) 144(3.87) 8(0.20) 0(0) 2(0.04)
Corneal staphyloma 9(0.29) 13(0.35) 18(0.44) 7(0.16) 8(0.17)
Acanthamoeba keratitis 10(0.33) 1(0.03) 9(0.22) 7(0.16) 6(0.13)
Exposure keratitis 0(0) 0(0) 3(0.07) 0(0) 0(0)

Discussion

Corneal diseases are a leading cause of blindness worldwide, second to cataract [1,15]. Due to the unbalanced global economy and ethnic differences, the causes of blindness, the proportion of the causes, the preferred surgical techniques of CT and the indications for surgery are not the same or even quite different in different countries and regions [1618]. Currently, China does not have a national eye bank union, so it is not easy to collect exact information on CT from all the hospitals and eye banks. Therefore, the general data on CT in China is unavailable now. The Chinese Ophthalmological Society is the most authoritative academic association in ophthalmology in China and its Corneal Disease Group (China Cornea Society) is the most authoritative group in the cornea disease field in China, whose members are experts on cornea-related clinical work and academic research. The members are very familiar with the hospitals in their own administrative unit, so they were entrusted to collect information from the hospitals in their own administrative units. The survey has covered most of the qualified hospitals in performing keratoplasties in the recent five years and it is estimated that the cases included in the survey accounted for more than 90% of all the corneal transplantations, so the results can represent the condition of keratoplasties in China.

According to our survey, the four leading indications for CT in China from 2014 through 2018 were corneal leukoma, bacterial keratitis, corneal dystrophies, and keratoconus, while the four leading indications for CT in America from 2005 to 2014 were PBK, keratoconus, Fuchs’ dystrophy, and repeat CT [4]. Analyses of the results show that there are both similarity and difference on the indications for CT between China and America.

Similarity: In both countries, keratoconus is among the top four indications of CT. Reason: Keratoconus occurs in all ethnic groups and it is related to heredity, therefore, the incidence rate of keratoconus in different countries is slightly different or comparable [1922].

Difference: In America, endothelial dysfunction (including PBK and Fuchs' dystrophy) is the main indication for CT, while in China, corneal leukoma, and infectious keratitis are the most common indications. Reasons: 1) The difference may be related to the economic development levels of the two countries. China is a developing country with an agricultural population of 800 million. The economic level and geographical conditions limit the promotion and application of agricultural machinery and the people still lack occupational safety awareness and protection measures. As a result, the risk of infectious keratitis caused by trauma in farming is high [23], therefore, corneal leukoma and infectious keratitis become the most common indications for CT in China. 2) America has a relatively long history in performing cataract surgeries and the total number of surgeries is large. The wide application of anterior chamber intraocular lenses in the 1980’s has accelerated the loss of endothelial cells after surgery, resulting in a large amount of PBK, which was one of the most common indications for CT from 2005 through 2014 [4]. Although the incidence rate of PBK has decreased worldwide these years with the development of facilities for cataract surgeries, the absolute number of people receiving cataract surgeries is still growing. According to the latest data, the cataract surgery rate in the United States was up to 10,000 in 2018, while in China, the rate was only 2000 to 3000 [2426].

The main surgical technique in the United States from 1980 to 2004 was PK. However, in the following 10 years, PK dramatically decreased from 95% in 2005 to 42% in 2014 and has been surpassed by various LK techniques (in the form of EK and ALK) in 2011 [4]. Analyzing the results of our survey, we found that from 2014 to 2016 the proportion of PK decreased by 4.71% while LK increased by 4.71%, and then in 2017 and 2018, the proportion of the techniques were relatively stable. In addition, to find the long-term trend of preferred techniques, the authors analyzed a single center study conducted by Shandong Eye Institute, covering 5316 cases of CT from 1996 to 2007 and found that in the twelve years, PK decreased from 76.0% to 61.8% while LK increased from 24.0% to 38.2% [27]. Therefore, it can be seen that the trend of preferred techniques of CT in China and America was similar in the past twenty years, with a decrease in PK and an increase in LK. The change of preferred technique from full thickness PK to LK can reduce the risk of surgery and the risk of immune rejection after surgery. In addition, the application of the new LK technique, such as deep anterior lamellar keratoplasty (DALK) and Descemet's membrane endothelial keratoplasty (DMEK), has made it possible for one or more people to share one donor cornea [28], which can reduce the burden of corneal blindness under the worldwide shortage of donor corneas.

Although in both China and America, the number of LK increased gradually, the respective proportion of ALK and EK and the indications were quite different. According to the statistical report of EBAA in 2014, ALK only accounted for 3.4% of various LK techniques while EK accounted for 96.6%. However, the results of our survey showed that ALK accounted for 83.03% while EK only accounted for 16.97% in China in 2018. The differences may be related to the establishment of eye bank association, the different indications in the two countries and the development of surgical techniques. 1) PK and EK require corneal tissue with high quality. In America, benefiting from the oversupply of donor corneas and the professional management by EBAA, the techniques can be performed with qualified corneas or even pre-cut grafts [29]. However, in China, there is a severe shortage of corneas nationwide [30,31]. No doubt that some eye banks may have corneas more than they need, but due to the lack of a unified management and distribution by a national eye bank association, the spare corneas in one eye bank can not be transferred to another bank for the maximum utilization in time. These corneas are usually dehydrated for a long period of preservation in the eye bank. After dehydration, the corneas can only be used for ALK. 2) In China, the indications for CT are mainly corneal leukoma and bacterial keratitis, which are not good indications for EK, while in America, the main indications for CT, PBK, and Fuchs’ dystrophy, are good indications for EK. 3) Due to the lamellar interface created during conventional LK, the postoperative visual acuity may be not as good as that after PK. The technical progresses have made it a reality for new techniques of LK to achieve a comparable visual acuity to PK [32]. In addition, for some diseases that were not typical indications for LK, such as chemical or thermal burns, herpes simplex keratitis scar, and bacterial keratitis scar, DALK is also applicable now, which contributes to the high proportion of LK [33,34].

Additionally, we noticed that the only common indication among the top four indications for CT in China and America was keratoconus, but the preferred techniques for it were quite different. Although there was an increase in ALK for keratoconus in America, PK remained the main surgical method, performed in 6224 patients while ALK only performed in 757 patients in 2014 [4]. In our survey, the proportion of ALK for keratoconus increased from 46.28% in 2014 to 71.37% in 2018 while PK decreased from 53.72% to 28.63%. The common practice of flattening the recipient bed in the process of ALK, which can affect the postoperative visual recovery due to the recipient bed wrinkles, may be a limiting factor for the application of ALK for patients with keratoconus in the past. With proper measures in surgery, the wrinkles can be avoided in the pupil area. Together with the application of DALK, the patients with keratoconus can obtain visual acuity comparable to PK [35]. Benefiting from improvements in techniques, even for cases with acute keratoconus, ALK can be performed before stroma scarring occurs. All these factors have contributed to the high proportion of ALK for keratoconus in China [36].

Due to immune rejection, chronic allograft dysfunction and late graft failure, the average survival time for graft after PK is only about 17 years. However, ALK can significantly lower the risk of chronic graft dysfunction and the graft can survive for about 49 years [37]. As most of the patients with keratoconus are teenagers, an early allograft dysfunction can affect their life. Therefore, ALK (including DALK), should be gradually popularized and applied worldwide for patients with keratoconus.

In our survey, information of CT from 2014 through 2018 in 64 hospitals were included. According to the data collected, the five largest hospital by number of CT surgeries completed 43.68% of the total number of CT surgeries in China and the five largest administrative units by number of CT surgeries performed 54.38% of the total number of CT surgeries in China. Except for No.1 Hospital of Xi’an City, the other 4 hospitals are in eastern China.

The geographical distributions of CT may correlate with the regional economy. The administrative units in eastern China have advantages over the units in central and western China. The rapid development of economy has opened people’s mind and increased their health needs. They are more willing to seek medical attention and more active in organ and tissue donation. In addition, the high economy level is the foundation of better transportation and medical level, which can benefit the patients and the cornea procurement.

Conclusions

In our survey, the data of CT in China from 2014 to 2018 were collected and analyzed to provide information for ophthalmologists at home and abroad to understand the condition of keratoplasty in China and then to conduct further studies. Although we have tried to contact as much hospitals as possible to collect information on CT, it is estimated that about 10% of the CT cases in China were not included. In addition, as this is the first time that a questionnaire has been designed to collect the general information of CT in China, limitations of the questionnaire exist inevitably. In the following five years, the questionnaire will be modified to collect more complete information (including the graft survival time) and use more standardized diagnoses and classification of indications to reflect the condition of CT in China comprehensively.

Overall, in China, the geographical distribution of keratoplasties and the number of keratoplasties performed in each hospital are quite unbalanced. To better serve the patients in central and western China, training for ophthalmologists, development of medical facility and popularization of donation knowledge at these regions are required. PK and ALK are the main surgical techniques for CT in China. Corneal leukoma, bacterial keratitis, and corneal dystrophies are the main indications for keratoplasties. These differences between China and America relate to the national conditions, economic development level, and ethnic characteristics.

Supporting information

S1 Table. Questionnaire of keratoplasty in China (Chinese and English version).

(PDF)

Acknowledgments

We sincerely thank all the hospitals and doctors who have contributed to the collection of the data.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

Funding: This study was supported by National Natural Science Foundation of China, grant number: 81570821 (HG), 81870639(HG); Key Project of National Natural Science Foundation of China, grant number: 81530027 (WS); Taishan Scholar Program, grant number: 20150215 (WS), 201812150(HG); and the Innovation Project of Shandong Academy of Medical Sciences (HG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Yu-Chi Liu

18 May 2020

PONE-D-20-09119

Keratoplasty in China: a 5-year review from 2014 to 2018

PLOS ONE

Dear Dr. Shi,

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Ting Huang2,3, Zhiqiang Pan2,4, Jie Wu2,5, Jianjiang Xu2,6, Jing Hong2,7,

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Tseten65, Jianping Ji3, Jin Yuan2, 3, Ying Jie4, Jun Xiang6, Yifei Huang2,13, Yuli

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**********

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**********

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**********

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**********

5. Review Comments to the Author

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Reviewer #1: This is a very extensive study with valuable information. The paper is well written. I have the following comments/suggestions to improve the scientific content.

The information of donor cornea preservation is incomplete. The authors should elaborate this aspect by providing specific information about the type of corneal storage medium and describe what is meant by the dry method.

The survey was based on a questionnaire. More details of the methodology of obtaining the information and the questions asked and collection of the responses can be provided.

Reviewer #2: Thank you for the opportunity to review this manuscript. It has the potential to be an important paper, as this is the first time such a comprehensive survey of keratoplasty in China has been attempted.

The current paper is a good draft, but I think there are multiple clarifications that need to be made before it can be published.

Background

1) many readers outside of China will not be familiar with the geography and the classification of provinces in China, so may I suggest that you explain

- how provinces and cities in China are categorised into "tiers"

- if possible, a map to show where the various participating hospitals are located - you may not be able to place all 64 hospitals on the map, but perhaps you can list the hospitals by geographical location?

Methods

2) Some detail needs to be provided on how corneas in China are obtained.

- I understand that use of foreign or imported tissue is highly restricted?

- the use of bio-engineered tissue is very interested, could you elaborate on how these tissues are engineered?

- proportion of fresh, versus frozen, versus bio-engineered tissue would give readers some context

3) a copy of the questionnaire used will be important, and included as an annex. An English translation would be appropriate for most readers.

4) Was there also information collected on graft survival, at least in the first year?

5) Information on the number of surgeries done - lines 276 to 296 - is best summarised in a table rather than written in the text. Similarly with the gender and age distribution.

6) Indications for surgery

- unfortunately, cornea leukoma is a rather rather term, unless there is a specific-definition used by the Chinese Cornea Society? Usually there is an underlying cause - congenital, trauma, infection. Would the authors be able to give further details?

- similarly, cornea perforation is very common, but it would be better to further tell readers if this is due to trauma or infection, ot other causes

- I am surprised bacteria keratitis is such a common indication, but fungal keratitis is not, even though fungal infections are as high as bacterial keratitis in China. Is this practice pattern (meaning that surgery is not done for fungal keratitis), or is it because it is classified under other indications - eg perforations?

7) ALK indications

- curious to see small numbers of corneal perforation - are these patch grafts?

- similarly I see ALK for pseuophakic bullous keratopathy

8) Discussion

- Could the authors comment how the availability of tissue also affects practice patterns?

for example, there could be much more ALK done in China vs the USA because of the lack of healthy fresh tissue for PK and EK

- could authors also comment on what more can be done to improve the CT situation - what this paper shows is that much more CT needs to be done to have any hope of helping the 3 million in China with cornea blindness - is bioengineered cornea a good option? what about training and facilities - 64 hospitals perform transplants, but many are done in smaller units and do much fewer transplants than the top 5 hospitals

Reviewer #3: This paper aims to analyze the trend of corneal transplants in China, focusing in particular on the diffusion of lamellar techniques and surgical indications and to compare the results with the trend in United States (US).

I found the manuscript interesting and original, since few data are available about corneal transplant in China.

I suggests the authors to include the survey as supplemental material.

Moreover, I suggest to include in the discussion the results of similar studies conducted in other countries, in addiction to the US situation.

The sentence at page 21 ,lines 377-328, should be corrected, since only EK surpassed the number of PK in US since 2011 (ALK is still inferior to PK).

**********

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Reviewer #1: Yes: Dr Radhika Tandon, MD, FRCOphth, FRCSEd; Professor of Ophthalmology, Co-Chairperson National Eye Bank, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. Also immediate past president Eye Bank Association of India (EBAI) and immediate past Vice President Association of Eye Banks of Asia (AEBA).

Reviewer #2: No

Reviewer #3: No

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PLoS One. 2020 Oct 15;15(10):e0239939. doi: 10.1371/journal.pone.0239939.r002

Author response to Decision Letter 0


1 Jul 2020

Dear editors and reviewers,

We are grateful to you for your time and constructive comments on our manuscript entitled "Survey report on keratoplasty in China: a 5-year review from 2014 to 2018". The comments and suggestions are very valuable and useful for improving the manuscript. We have carefully implemented the comments and suggestions and wish to submit this revised version for further consideration in the journal. Below, we also provide point-by-point responses explaining how we have addressed each of the comments.

Looking forward to hearing from you soon.

Thank you and with kindest regards.

Yours Sincerely,

Weiyun Shi

On behalf of co-authors

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

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Answer: We have modified the manuscript according to the templates.

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

Answer: We have included a copy of the questionnaire in both Chinese and English as supporting information.

3. Please modify the title to ensure that it is meeting PLOS’ guidelines (https://journals.plos.org/plosone/s/submission-guidelines#loc-title). In particular, the title should be "specific, descriptive, concise, and comprehensible to readers outside the field" and in this case it is not informative and specific about your study's scope and methodology.

Answer: We have modified the title to “Survey report on keratoplasty in China: a 5-year review from 2014 to 2018” according to the guidelines. If the title should be further changed, would you please give us some suggestion? Thank you very much.

4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

Answer: The ORCID ID of the corresponding author has been added. Thank you.

5. Please amend the manuscript submission data (via Edit Submission) to include authors:

Ting Huang2,3, Zhiqiang Pan2,4, Jie Wu2,5, Jianjiang Xu2,6, Jing Hong2,7,

Wei Chen,2,8, Huping Wu9, Qian Kang10, Lei Zhu2,11, Lingling Fu12, Liqiang Wang2,13,

Guigang Li2,14, Zhihong Deng15, Hong Zhang2,16, Hui Xu17, Qingliang Zhao18,

Hongshan Liu19, Linnong Wang2,20, Baihua Chen2,21, Xiuming Jin2,22, Minghai

Huang23, Jizhong Yang24, Minghong Gao2,25, Wentian Zhou26, Hanping Xie2,27, Yao

Fu2,28, Feng Wen29, Changbo Fu30, Shaozhen Zhao2,31, Yanning Yang2,32, Yanjiang

Fu33, Tao Yao34, Chaoqing Wang35, Xiaonan Sun36, Xiaowei Gao2,37, Maimaitiming

Reziwan38, Yingping Deng2,39, Jian Li40, Limei Liu 41, Bo Zeng42, Lianyun Bao43, Hua

Wang 2,44, Lijun Zhang2,45, Zhiyuan Li46, Zhijian Yin47, Yuechun Wen 48, Xiao Zheng

49, Liqun Du 50, Zhenping Huang 51, Xunlun Sheng 52, Hui Zhang2,53, Lizhong Chen 54,

Xiaoming Yan 2,55, Xiaowei Liu 56, Wenhui Liu 57, Yuan Liu 58, Liang Liang 59,

Pengcheng Wu 60, Lijun Qu61, Jinkui Cheng62, Hua Zhang63, Qige Qi64, Yangkyi

Tseten65, Jianping Ji3, Jin Yuan2, 3, Ying Jie4, Jun Xiang6, Yifei Huang2,13, Yuli

Yang2,27, Ying Li2,56, Yiyi Hou1, Tong Liu1, Lixin Xie.

Answer: Thank you very much. Information of all the authors has been added to the submission system.

6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Answer: Thank you very much. We have included the caption for the supporting information at the end of the manuscript and updated the in-text citation.

Reviewers' comments:

Comments to the Author

Reviewer #1: This is a very extensive study with valuable information. The paper is well written. I have the following comments/suggestions to improve the scientific content.

The information of donor cornea preservation is incomplete. The authors should elaborate this aspect by providing specific information about the type of corneal storage medium and describe what is meant by the dry method.

Answer: Thank you very much for raising this point. Limited by the requirements on article length, we have not given comprehensive information of donor cornea preservation in the manuscript that we submitted. In fact, there is much information that should be reported, so after careful discussion, in this revised manuscript, we decided to delete all the information about donor cornea preservation and in the near future, we will write an article reporting the survey results on cornea preservation and compare them with those in America.

The survey was based on a questionnaire. More details of the methodology of obtaining the information and the questions asked and collection of the responses can be provided.

Answer: Thank you very much for your suggestion. In the revised manuscript, we have added the questionnaire as supporting information.

Reviewer #2: Thank you for the opportunity to review this manuscript. It has the potential to be an important paper, as this is the first time such a comprehensive survey of keratoplasty in China has been attempted.

The current paper is a good draft, but I think there are multiple clarifications that need to be made before it can be published.

Background

1) many readers outside of China will not be familiar with the geography and the classification of provinces in China, so may I suggest that you explain

- how provinces and cities in China are categorised into "tiers"

- if possible, a map to show where the various participating hospitals are located - you may not be able to place all 64 hospitals on the map, but perhaps you can list the hospitals by geographical location?

Answer: Thank you very much for your suggestion. We agree with you on your opinion that many foreigners are not familiar with the classification of provinces in China, so in the manuscript, to avoid confusing the readers, we use “provincial-level administrative units” instead of terms like “province” and “municipality directly under the central government”.

Methods

2) Some detail needs to be provided on how corneas in China are obtained.

- I understand that use of foreign or imported tissue is highly restricted?

- the use of bio-engineered tissue is very interested, could you elaborate on how these tissues are engineered?

- proportion of fresh, versus frozen, versus bio-engineered tissue would give readers some context

Answer: Thank you very much for raising this point. As you said, the use of foreign and imported tissue is highly restricted. In China, the procurement, management and use of cornea tissue are more standardized in recent years. However, there is still a huge shortage of corneas in China, so ophthalmologists are making efforts to look for alternatives. Prof. Weiyun Shi and his team have made breakthrough in the field of bio-engineered cornea and published articles about decellularized porcine cornea (Shi, W, Zhou, Q, Gao, H, Li, S, Dong, M, & Wang, T, et al. (2019). Protectively decellularized porcine cornea versus human donor cornea for lamellar transplantation. Advanced Functional Materials, 29(37), 1902491.1-1902491.12. Dong, Muchen & Zhao, Long & Wang, Fuyan & Hu, Xiaoli & Li, Hua & Liu, Ting & Zhou, Qingjun & Shi, Weiyun. (2019). Rapid porcine corneal decellularization through the use of sodium N-lauroyl glutamate and supernuclease. Journal of Tissue Engineering. 10. 204173141987587. 10.1177/2041731419875876.). In our study, the main preservation methods of donor corneas were mid-term preservation (29 252, 79.89%), preservation by dehydration (5 864, 16.01%) and preservation in moist chamber (1 500, 4.10%). We found that there is much information that can be reported based on the results of the survey, so we decided to delete all the information about cornea procurement and preservation in this article and write an article thoroughly reporting the information.

3) a copy of the questionnaire used will be important, and included as an annex. An English translation would be appropriate for most readers.

Answer: Thank you very much for your suggestion. We have added a copy of questionnaire as supporting information.

4) Was there also information collected on graft survival, at least in the first year?

Answer: Thank you very much for raising this point. To be honest, we have not collected information on graft survival. In the future, when we do this survey, we will improve the questionnaire and collect information on CT.

5) Information on the number of surgeries done - lines 276 to 296 - is best summarised in a table rather than written in the text. Similarly with the gender and age distribution.

Answer: Thank you very much for your suggestion. We have expressed the information in a table.

6) Indications for surgery

- unfortunately, cornea leukoma is a rather rather term, unless there is a specific-definition used by the Chinese Cornea Society? Usually there is an underlying cause - congenital, trauma, infection. Would the authors be able to give further details?

Answer: Thank you very much for raising this point. According to the survey results collected from the hospitals, we can not give detailed information on the underlying causes. We have called the hospital and they said that for some patients, the underlying causes were hard to diagnosed, so cornea leukoma was the indication for their surgeries. The cases whose causes of cornea leukoma were diagnosed have been included in the corresponding indications.

- similarly, cornea perforation is very common, but it would be better to further tell readers if this is due to trauma or infection, ot other causes

Answer: Thank you very much for raising this point. According to the survey results collected from the hospitals, we can not give detailed information on the underlying causes. We have called the hospital and they said that for some patients, the underlying causes were hard to diagnosed, so cornea perforation was the indication for their surgeries. The cases whose causes of cornea perforation were diagnosed have been included in the corresponding indications.

- I am surprised bacteria keratitis is such a common indication, but fungal keratitis is not, even though fungal infections are as high as bacterial keratitis in China. Is this practice pattern (meaning that surgery is not done for fungal keratitis), or is it because it is classified under other indications - eg perforations?

Answer: Thank you very much for your question. In the survey, fungal keratitis was not classified under other indications.

7) ALK indications

- curious to see small numbers of corneal perforation - are these patch grafts?

- similarly I see ALK for pseuophakic bullous keratopathy

Answer: Thank you very much for raising this point. The main reason for ALK performed for patients with corneal perforation and pseuophakic bullous keratopathy was the shortage of fresh cornea tissue in China, so ALK was used as an alternative to save the patients’ eyes. Besides, for patients with pseuophakic bullous keratopathy, PK and EK are the preferred methods, but without qualified corneas, ALK can be performed to alleviate their pain.

8) Discussion

- Could the authors comment how the availability of tissue also affects practice patterns?

for example, there could be much more ALK done in China vs the USA because of the lack of healthy fresh tissue for PK and EK

Answer: Thank you very much for raising this point. The cornea types that are available do influence the surgery types the ophthalmologists selected. Benefiting from the questions and suggestions from the reviewers, we realized that we need to reporting more valuable information on cornea procurement and preservation, which influences the surgery patterns selected. We should not waste the hard-won information from the survey, so in addition to this article, we decided to write another article reporting this aspect comprehensively.

- could authors also comment on what more can be done to improve the CT situation - what this paper shows is that much more CT needs to be done to have any hope of helping the 3 million in China with cornea blindness - is bioengineered cornea a good option? what about training and facilities - 64 hospitals perform transplants, but many are done in smaller units and do much fewer transplants than the top 5 hospitals

Answer: Thank you very much for raising these points. Measures should be taken to improve the CT situation in China. For example, the society can pay more attention to the publicity of cornea donation and the government and professional organizations can carry out more training. A course on corneal transplantation led by Prof. Weiyun Shi has training more than 200 ophthalmologists.

Bio-engineered cornea is a good option, which can ease the situation of cornea shortage in China. Bio-engineered corneas do not need to be stored in eye banks, so it is more convenient to use.

To narrow the gap between the hospitals, we think that developing economy is of great importance.

Reviewer #3: This paper aims to analyze the trend of corneal transplants in China, focusing in particular on the diffusion of lamellar techniques and surgical indications and to compare the results with the trend in United States (US).

I found the manuscript interesting and original, since few data are available about corneal transplant in China.

I suggests the authors to include the survey as supplemental material.

Moreover, I suggest to include in the discussion the results of similar studies conducted in other countries, in addiction to the US situation.

The sentence at page 21 ,lines 377-328, should be corrected, since only EK surpassed the number of PK in US since 2011 (ALK is still inferior to PK).

Answer: Thank you very much for your careful review. We have added the questionnaire as supporting information.

Comparing the results in China with the results in other countries can better reflect the differences and provide more information for readers, but this survey was designed referring to the EBAA report, so we only compared the results with those in America. At the beginning of the study, we have compared reports and articles of different countries in this field. EBAA was the one who reported comprehensively and annually, so we decided to compare the situation in China with the situation in America.

In the sentence at page 21, lines 377-378, “various LK” means ALK and EK. Thank you for pointing out. To express the meaning more clearly, we have modified the expression in the sentence.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Yu-Chi Liu

3 Aug 2020

PONE-D-20-09119R1

Survey report on keratoplasty in China: a 5-year review from 2014 to 2018

PLOS ONE

Dear Dr. Shi,

Thank you for submitting your manuscript to PLOS ONE. The reviewers have raised some comments and we would like to invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Yu-Chi Liu, M.D

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: N/A

**********

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The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: (No Response)

Reviewer #2: No

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have addressed the concerns raised. Minor editorial corrections and language changes are required. For example one-center can be changed to single center. Line 468-471 the sentence "Overall, in China, the geographical ...weak in CT" in the conclusion needs to be re-written as it is not clear.

Reviewer #2: Thank you once again for the opportunity to review this paper, as I was Reviewer 2 for the first submission.

I appreciate that the authors have made some of the amendments as I have suggested, including summarising the data in tables.

Other information that I felt would have made this a more complete paper appears to not be available, based on the methods and on how the questionnaire was designed. I think it is therefore important to include a section of the paper to address the limitations of the study - namely that this was a retrospective study where information is incomplete, diagnoses and classification of indications are not standardised (eg the meaning of cornea leukoma), and that outcome data in terms of graft survival was not obtained.

Reviewer #3: (No Response)

**********

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Reviewer #3: No

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PLoS One. 2020 Oct 15;15(10):e0239939. doi: 10.1371/journal.pone.0239939.r004

Author response to Decision Letter 1


19 Aug 2020

Dear Dr. Liu and reviewers,

We would like to give our great thanks to you and all the reviewer, for your valuable comments on our manuscript entitled "Survey report on keratoplasty in China: a 5-year review from 2014 to 2018". Thank you for your suggestions and efforts to make the article better. We have carefully implemented the comments and suggestions and wish to submit this revised version for further consideration in the journal. Below, we provide point-by-point responses explaining how we have addressed each of the comments.

Looking forward to hearing from you soon.

Thank you and with kindest regards.

Yours Sincerely,

Weiyun Shi

On behalf of co-authors

1. Reviewer #1: The authors have addressed the concerns raised. Minor editorial corrections and language changes are required. For example, one-center can be changed to single center. Line 468-471 the sentence "Overall, in China, the geographical ...weak in CT" in the conclusion needs to be re-written as it is not clear.

Answer: Thank you very much for your time and suggestions. We have read the article carefully and thoroughly to avoid typographical and grammatical errors. “One-center” has been changed to “single center”. The sentence has been rewritten.

2. Reviewer #2: Thank you once again for the opportunity to review this paper, as I was Reviewer 2 for the first submission. I appreciate that the authors have made some of the amendments as I have suggested, including summarizing the data in tables. Other information that I felt would have made this a more complete paper appears to not be available, based on the methods and on how the questionnaire was designed. I think it is therefore important to include a section of the paper to address the limitations of the study - namely that this was a retrospective study where information is incomplete, diagnoses and classification of indications are not standardized (eg the meaning of cornea leukoma), and that outcome data in terms of graft survival was not obtained.

Answer: Thank you very much for your valuable suggestions on the previous manuscripts. We benefit a lot from your comments and we have modified the article accordingly. No doubt there are limitations in the questionnaire and they are hard to be corrected for the survey from 2014 to 2018. Therefore, we adopted your advice and added sentences at the end of the manuscript to address the limitations of the study. We appreciate your efforts to make the article and the questionnaire better.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 2

Yu-Chi Liu

16 Sep 2020

Survey report on keratoplasty in China: a 5-year review from 2014 to 2018

PONE-D-20-09119R2

Dear Dr. Shi,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Yu-Chi Liu, M.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Acceptance letter

Yu-Chi Liu

5 Oct 2020

PONE-D-20-09119R2

Survey report on keratoplasty in China: a 5-year review from 2014 to 2018

Dear Dr. Shi:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Yu-Chi Liu

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Questionnaire of keratoplasty in China (Chinese and English version).

    (PDF)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    All relevant data are within the manuscript and its Supporting Information files.


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