Global trends and prospects of endothelial keratoplasty from 2004 to 2023: a bibliometric analysis

Abstract

Background:

Endothelial keratoplasty (EK) has revolutionized the treatment of corneal diseases by offering a less invasive alternative to traditional full-thickness keratoplasty. Over the past decades, EK techniques have evolved significantly, improving surgical outcomes, expediting recovery, and reducing postoperative complications. Nevertheless, challenges such as postoperative rejection and endothelial cell loss persist. This study utilizes bibliometric analysis to map the current research landscape of EK and identify future directions.

Methods:

A systematic bibliometric analysis was conducted on publications spanning from 2004 to 2023, retrieved from the Web of Science Core Collection. Key metrics such as annual publication and citation counts, contributions by countries and institutions, influential journals, authors and cited authors, highly cited references, co-citation references, and keyword trends were extracted and analyzed using CiteSpace and VOSviewer, Microsoft Excel, Bibliometrix, Scimago Graphica, and Microsoft Excel.

Results:

A total of 2676 relevant publications were identified from 2004 to 2023. While the first 5 years saw the limited number of publications in this field, a marked increase in publications has occurred throughout these years. The United States, Germany, and England were the leading contributors. Marianne O. Price emerged as the most prolific author, with Francis W. Price Jr. most frequently cited among the top contributors. Major publishing journals included Cornea, Ophthalmology, and American Journal of Ophthalmology. Leading institutions included the Netherlands Institute for Innovative Ocular Surgery and the Legacy Devers Eye Institute. VOSviewer keyword clustering revealed 13 thematic clusters, with trending keywords such as “risk factors” and “tissue,” suggesting emerging focal points.

Conclusions:

The bibliometric analysis highlights the dynamic evolution and key research areas of EK and ocular disease management. Leveraging these insights is crucial for advancing clinical practice and driving further innovation in the field.

Introduction

The cornea, a transparent dome-shaped structure covering the front of the eye, is essential for vision as it refracts light onto the retina[1]. It consists of five distinct layers: the outermost epithelium, Bowman’s layer, stroma, Descemet’s layer, and innermost endothelium^[2,3]. Dysfunction of the corneal endothelium often leads to corneal edema and vision impairment, necessitating surgical intervention.

HIGHLIGHTS

• A 20-year bibliometric analysis reveals global research trends in endothelial keratoplasty.

• The United States, Germany, and UK dominate EK output and drive cross-national collaboration.

• Emerging hotspots include exosome-based therapies and advanced graft techniques.

• CiteSpace and VOSviewer map research clusters and evolving thematic focus in EK.

• Findings highlight key gaps and future priorities in EK innovation and global practice.

Endothelial keratoplasty (EK) has emerged as a crucial therapeutic method for addressing corneal diseases[4]. The minimally invasive technique, renowned for less surgical trauma and faster recovery, has become the preferred choice over traditional full-thickness corneal transplantation[5]. Over the years, there have been substantial advancements in EK techniques, progressing from Descemet’s Stripping Endothelial Keratoplasty (DSEK) to more recent versions such as Descemet’s Membrane Endothelial Keratoplasty (DMEK). These advancements have significantly enhanced corneal surgery[5], which not only improve surgical success rates but also mitigate postoperative complications, benefiting a larger variety of patients undergoing corneal transplantation^[4,5]. Nevertheless, the clinical implementation of EK still faces challenges, including postoperative problems such rejection reactions, loss of endothelial cells, and foreign body sensation, which remain to be major obstacles to achieving long-term efficacy^[4,6,7]. Addressing these issues demands a comprehensive exploration and analysis of EK to optimize outcomes and enhance patient well-being^[4,6,7]. EK has revolutionized the treatment of corneal endothelial dysfunction and lowered the threshold for treatment by providing rapid visual rehabilitation and setting a high standard for safety and efficacy. Over time, EK techniques have evolved toward the use of thinner tissue to optimize visual outcomes; refinements have facilitated donor tissue preparation, handling, and attachment; and adaptations have expanded utilization in eyes with challenging ocular anatomy. Despite early concerns about graft longevity, emerging 10-year endothelial cell loss and graft survival data have been encouraging. Yet, a shortage of human donor corneas restricts utilization in many areas of the world and is spurring exploration into keratoplasty alternatives. Further work is needed to expand the donor supply, minimize impediments to adoption, optimize graft survival, and improve refractive predictability.

Bibliometric analysis, a well-established statistical method for evaluating published literature, has garnered considerable attention[8]. First proposed by American bibliographers in 1969[9], this method combines qualitative and quantitative methodologies to extract essential insights from publications[10]. This methodology facilitates the identification of cutting-edge areas of research and provides insights into the geographical distribution of countries/regions, authors, and journals in a certain field[11]. As the research interest in the therapeutic potential of EK for corneal disorders continues to grow, a significant amount of literature, including systematic reviews and meta-analyses, has been published[12]. However, few bibliometric analyses have investigated the hotspots and frontiers of research in this field.

This study seeks to bridge that gap by giving a comprehensive analysis of the quantitative and visual data available in the global literature on EK. By conducting a comprehensive examination of pertinent articles released globally between 2004 and 2023, we strive to identify emerging trends and potential hotspots. This analysis aims to enable a concise examination of EK research and provide prognostications regarding future trends, thereby establishing a framework for guiding future research directions and advancements.

In line with the TITAN 2025 guidelines for transparency in reporting AI tools used in scientific work, we confirm full compliance with all ethical and technical reporting standards[13].

Methods

Data collection and search strategy

Publications were retrieved from the Web of Science Core Collection (WoSCC) database[14]. Renowned for its extensive coverage of scholarly perspectives, comprehensive database, and user-friendly interface, WoS offers advantages such as broad applicability, minimal usage restrictions, and robust information evaluation tools[15]. The search query was meticulously designed to capture a diverse array of literature related to EK. The following was our formula for retrieval: TS = (“EK” OR “Endothelial Keratoplasty” OR “DMEK” OR “Descemet Membrane Endothelial Keratoplasty” OR “DSAEK” OR “Descemet Stripping Automated Endothelial Keratoplasty” OR “DSEK” OR “Descemet Stripping Endothelial Keratoplasty”). The period of time covered was 1 January 2004 to 31 December 2023. To uphold scientific rigor, stringent exclusion criteria were applied to exclude irrelevant publications. A total of 2676 publications were included in the analysis, encompassing only original articles and reviews. Retrieval and export were completed within a single day on 24 March 2024, ensuring accuracy and minimizing potential bias from database updates. To enhance methodological reliability, the search procedure and findings were independently validated by two authors. Both researchers independently extracted relevant data from the selected publications using a standardized data extraction form. Discrepancies were resolved through discussion until a consensus was reached.

Bibliometric software

CiteSpace (version 6.3. R1), developed by Chaomei Chen at Drexel University, Philadelphia, PA, United States, is a widely used software tool that enables comprehensive analysis and visualization of scholarly literature[16]. With its advanced algorithms, CiteSpace enables researchers to identify co-citation networks, aiding in the identification of important themes, seminal papers, and evolving trends over time. Through visualizing the interconnections between articles and authors, CiteSpace enhances scholars’ comprehension of the collaborative nature of scientific inquiry and the evolution of knowledge within specific research topics by illustrating the connections between publications and authors. Additionally, VOSviewer (version 1.6.11), developed by Nees Jan van Eck and Ludo Waltman at Leiden University, Leiden, the Netherlands, provides scholars with a sophisticated platform for bibliometric analysis[17]. Through the utilization of these software platforms, researchers have the ability to uncover new insights, monitor the development of research trends, and contribute to the progression of knowledge in specialized fields like endothelial keratoplasty. Additional tools included Bibliometrix (R 4.1.1), Scimago Graphica, and Microsoft Excel for quantitative analysis and graphical enhancement.

Data analysis

Initiating a bibliometric analysis on EK involves retrieving data from the WOS database. Subsequently, functions such as “Analyze Results” and “Citation Report” are utilized to extract vital statistics, including annual production, WOS categories, and quality ratings based on various factors such as country, institution, author, and journal. The data are subsequently imported into CiteSpace and VOSviewer for both quantitative and qualitative analyses^[15,16]. To maintain data integrity, CiteSpace’s “eliminating duplicates function” is employed to curate the dataset and eliminate redundant entries[15]. Publication and citation trends are extracted from the citation reports provided by WOS, providing insights into the temporal dynamics of scholarly output in the field. Subsequently, CiteSpace is utilized to conduct a comprehensive study, which includes identifying distribution patterns among countries/regions, journals, and co-cited academic journals, as well as authors and co-cited authors[15]. Furthermore, the software facilitates the detection of keyword bursts and trends, along with an examination of co-cited references, thereby identifying developing research topics and prominent literature in the field[15]. Meanwhile, VOSviewer visualizes the network of hotspots (keywords) related to endothelial keratoplasty research. Co-occurrence analysis divides hotspots into discrete clusters and color-codes them based on their temporal history, resulting in a clear visual depiction of the evolving research landscape[16]. Detailed methods for data enrollment and the analytical process are depicted in Fig. 1, ensuring transparency and reproducibility in the bibliometric study.

Figure 1.

Data screening flow chart and steps of bibliometric analysis. The literature search was performed on the Web of Science Core Collection.

Artificial intelligence use declaration

In accordance with the TITAN 2025 guidelines[13], we declare that no generative artificial intelligence (AI) tools were used in the development or writing of this manuscript. All analyses were performed using non-generative bibliometric software including CiteSpace (v6.3.R1), VOSviewer (v1.6.11), Bibliometrix (R 4.1.1), and Microsoft Excel. These tools were used solely for data analysis and visualization. All figures and interpretations were verified by the authors. The TITAN 2025 guideline has been cited in the “Introduction” section and a completed checklist has been submitted.

Results

Trends of publications and citations

6176 publications were retrieved from the WoSCC database, with publication dates from 2004 through 2023. Next, the publication types were limited to original and review articles. Finally, 2676 publications were included in this analysis. Figure 2 depicts the annual publication and citation in the field of EK. Between 2004 and 2023, there was a substantial growth in both the quantity of published works and the frequency at which they were cited. Prior to 2010, there was a relatively small amount of scholarly work on this subject. However, this pattern gradually shifted over the years. The significant surge in research output post-2010 was particularly remarkable. In 2021, there were 258 publications on EK, with a total citation count of 9336. This surpasses the amount of articles and citations in prior years, highlighting the substantial effect of this topic on current ophthalmic research. The findings suggest that EK, a significant field in ophthalmic research, has garnered considerable scholarly interest and ongoing research funding.

Figure 2.

The annual number of publications and citations per year on endothelial keratoplasty.

Distribution of countries

When studying bibliometric analysis primarily focused on EK, it is evident that there are significant patterns in the distribution of countries. EK research emerged from 78 different countries, with a diverse collection of publications in the combined corpus.

The comprehensive analysis, as indicated in Table 1, emphasizes the main contribution originating from the United States, comprising 23.99% of the overall articles. Germany and England have become prominent contributors to the academic discourse on endothelial keratoplasty, with Germany representing 15.67% and England representing 10.89% of the published articles. Moreover, these countries exert a substantial impact that extends beyond the quantity of papers they generate, as evidenced by citation metrics. The United States is the country that is referenced most often, and publications from this region receive a substantial number of citations, amounting to 24 907. This emphasizes the nation’s prominent stance in the field. Germany and England had citation numbers of 7992 and 4506, respectively, which were similarly significant.

Table 1.

Top 15 countries with publications on endothelial keratoplasty

Rank	Country	Number of publications		Number of citations
		Documents	Percentage
1	United States	817	23.99	24 907
2	Germany	408	11.98	7992
3	England	216	6.34	4506
4	India	210	6.17	2012
5	Italy	192	5.64	2961
6	The Netherlands	184	5.40	6875
7	Japan	167	4.90	2739
8	China	103	3.02	1100
9	Singapore	101	2.97	3568
10	Spain	98	2.88	1088
11	Canada	93	2.73	1565
12	France	88	2.58	1112
13	Israel	80	2.35	845
14	Australia	61	1.79	920
15	Greece	52	1.53	666

Figure 3A and Fig. 3B depict the distribution network in the country, with the United States being showcased as a major node, emphasizing its pivotal role in the collaborative network. Nodes that have purple rings on their outside edge, which include countries like the United States, Germany, England, Italy, and Spain, demonstrate a notable level of importance. These findings indicate that research conducted in these nations has significantly advanced the field of endothelial keratoplasty and has facilitated connections between various subdomains within the subject. The noteworthy collaboration between the United States and several nations, including Germany, England, and India, highlights the global extent of research partnerships in enhancing understanding in endothelial keratoplasty.

Figure 3.

The active countries and cooperative relationships in this field. (A) VOSviewer visualization map of the co-cited authors. VOSviewer automatically classified co-authors with over 15 citations into three sections (the green, red, and blue sections, respectively). (B) Country distributions of the publications. Countries with purple rings on the periphery have a high centrality. (C) World map representing the scientific production by countries. The color intensity reflects the volume or frequency of publications, with darker shades indicating higher publication numbers, and lighter shades or grays indicating fewer or no contributions. (D) The cooperative relationships of countries. The size of the circles represents the number of posts, the lines between the circles represent mutual cooperation, and the darker the circle is, the more international communications and collaborations it has. (E) The cooperation of the country/region contributed to publications.

In addition, we conducted a study to assess international cooperation by analyzing the distribution of nations and their collaboration (as shown in Fig. 3C, 3D, and 3E). According to the collaboration map, the United States had the highest total connection strength (296) and had the most extensive national cooperation network. Germany and England both had substantial national cooperation networks.

Distribution of institutions

The joint endeavor in this field is led by institutions from the Netherlands, the United States, England, India, and Singapore, as seen in Table 2 and Fig. 4A. Each of these institutions has made significant contributions to the corpus of knowledge. The Netherlands Institute For Innovative Ocular Surgery is leading the way in this academic pursuit, showing a strong commitment to research in endothelial keratoplasty. Two notable organizations, Legacy Devers Eye Institute and Price Vision Group, have significantly advanced our knowledge and treatment of corneal endothelial disorders. Moreover, an analysis of the frequency of citations demonstrates the significant influence of particular institutions on this scientific discussion (Fig. 4B). Institutions like the Cornea Research Foundation of America demonstrate exceptional citation impact, representing worldwide recognition for their contributions to research on EK. A cooperative relationship institutions map was generated to depict the collaborative interactions among cited institutions.

Table 2.

Top 15 institutions in the studies of endothelial keratoplasty

Rank	Organization	Country	Publications	Citations
1	The Netherlands Institute For Innovative Ocular Surgery	The Netherlands	110	5529
2	Legacy Devers Eye Institute	United States	91	3887
3	Price Vision Group	United States	82	6840
4	Singapore National Eye Centre	Singapore	80	2889
5	Cornea Research Foundation of America	United States	78	6924
6	University of Cologne	Germany	78	1791
7	Singapore Eye Research Institute	Singapore	74	2727
8	University of Toronto	Canada	65	1266
9	Melles Cornea Clinic	The Netherlands	64	2820
10	Tel Aviv University	Israel	62	712
11	All India Institutes of Medical Sciences	India	51	672
12	L.V. Prasad Eye Institute	India	50	351
13	Johns Hopkins University	United States	49	789
14	VisionGift	United States	48	1190
15	The University of Liverpool	England	47	492

Figure 4.

Distribution of publications and citations from different institutions. (A) VOSviewer visualization map of the co-cited authors. Node size indicates the number of publications, while the thickness of the link positively correlates with the strength of cooperation. (B) Cooperative network visualization map of institutions engaged in endothelial keratoplasty research. Node size indicates the number of publications, and the thickness of the link positively correlates with the cooperation strength. (C) Cooperative network visualization map of cited institutions for endothelial keratoplasty.

Analysis of journals

Table 3 depicts how the top 10 frequently cited and highly productive journals were assessed independently using VOSviewer. The gathered literature spans 2676 journals, the most of which are published by Cornea (17 753 citations, 260 papers), Ophthalmology (11 401 citations, 137 papers), American Journal of Ophthalmology (7543 citations, 316 papers), Journal of Cataract and Refreactive Surgery (4131 citations, 157 papers), and British Journal of Ophthalmology (3233 citations, 305 papers). These journals are well respected in the domains of immunology, microbiology, ophthalmology, and transdisciplinary sciences.

Table 3.

Top 15 journals in the studies of endothelial keratoplasty

	Journals	Citations	Publications	IF (2023)	JCR	H-index
1	Cornea	17 753	260	2.8	Q2	108
2	Ophthalmology	11 401	137	13.7	Q1	217
3	American Journal of Ophthalmology	7543	316	4.2	Q1	171
4	Journal of Cataract and Refreactive Surgery	4131	157	2.8	Q2	129
5	British Journal of Ophthalmology	3233	305	4.1	Q1	137
6	Investigative Ophthalmology & Visual Science	2795	252	4.4	Q1	196
7	JAMA Ophthalmology	2768	115	8.1	Q1	180
8	Graefe’s Archive for Clinical and Experimental Ophthalmology	1255	382	2.7	Q2	89
9	Current Opinion in Ophthalmology	1184	80	3.7	Q1	79
10	Eye	1060	385	3.9	Q1	86
11	Journal of Refractive Surgery	961	97	2.4	Q2	89
12	Acta Ophthalmologica	921	177	3.4	Q2	77
13	Survey of Ophthalmology	744	87	5.1	Q1	120
14	Experimental Eye Research	596	303	3.4	Q2	112
15	Klinische Monatsblätter für Augenheilkunde	555	146	0.8	Q4	35

Journal Impact Factor (IF) is another statistic that indicates a journal’s effect and significance in specific domains, determined as the average citation count of the journal’s publications in a given year[17]. According to IF 2023, Ophthalmology (13.7) stands out among the top 15 published journals. Moreover, as per the Journal Citation Reports (JCR) in 2022 (Clarivate, United Kingdom), most major journals are classified in Quartile 1 (Q1) and Quartile 2 (Q2) (Table 3).

Analysis of authors and cited authors

Table 4 and Fig. 5A illustrate a review of prolific authors in endothelial keratoplasty literature, revealing a group of scientists whose contributions have considerably unveil a group of scientists whose contributions have significantly enriched the scholarly landscape. These authors, who predominantly originate from the United States, the Netherlands, Germany, Singapore, and Italy, highlight the global reach and effect of research endeavors in endothelial keratoplasty. Scholars such as Marianne O. Price from the Netherlands Institute for Innovative Ocular Surgery (NIIOS) and Francis Price Jr. from Price Vision Group show the different knowledge contributing to breakthroughs in this specialized subject.

Table 5.

Top 10 highest cited papers on endothelial keratoplasty

Rank	Title	Journal	Type	Authors	Year	Citations
1	Descemet membrane endothelial keratoplasty: safety and outcomes: A Report by the American Academy of Ophthalmology	Ophthalmology	Review	Sophie X Deng et al	2018	209
2	Descemet-stripping automated endothelial keratoplasty	Cornea	Article	Mark S Gorovoy et al	2006	195
3	Descemet’s stripping with endothelial keratoplasty in 200 eyes: Early challenges and techniques to enhance donor adherence	Journal of Cataract & Refractive Surgery	Article	Francis W Price Jr et al	2006	189
4	Descemet’s stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology	Ophthalmology	Review	W Barry Lee et al	2009	172
5	Descemet membrane endothelial keratoplasty versus descemet stripping automated endothelial keratoplasty	American Journal of Ophthalmology	Article	Theofilos Tourtas et al	2012	148
6	Risk of corneal transplant rejection significantly reduced with descemet’s membrane endothelial keratoplasty	Ophthalmology	Article	Arundhati Anshu et al	2012	140
7	Descemet’s stripping with endothelial keratoplasty: comparative outcomes with microkeratome-dissected and manually dissected donor tissue	Ophthalmology	Article	Marianne O. Price et al	2006	136
8	Visual acuity, refractive error, and endothelial cell density six months after descemet stripping and automated endothelial keratoplasty (DSAEK)	Cornea	Article	Steven B. Koenig et al	2007	122
9	Interim results of the United States investigational device study of the Ophtec capsular tension ring	Ophthalmology	Article	Francis W Price Jr et al	2005	121
10	Descemet’s membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival	Ophthalmology	Article	Marianne O. Price et al	2009	116

Table 4.

Top 10 prolific authors and co-cited authors in the studies of endothelial keratoplasty

Rank	Author	Country	Publications	Citations	Co-cited author	Country	Citations
1	Marianne O. Price	United States	75	5920	Francis W. Price Jr.	United States	2447
2	Gerrit R. J. Melles	The Netherlands	112	5256	Gerrit R. J. Melles	The Netherlands	2148
3	Francis Price Jr.	United States	64	4765	Terry Ma	United States	2095
4	Lisanne Ham	The Netherlands	58	3337	Francis W. Price	United States	1192
5	Mark A. Terry	United States	78	3272	Isabel Dapena	The Netherlands	755
6	Claus Cursiefen	Germany	81	3095	Massimo Busin	Italy	751
7	Isabel Dapena	The Netherlands	54	2837	Anshu A. Raj	United States	714
8	Friedrich E. Kruse	Germany	41	2065	Mark S. Gorovoy	United States	600
9	Jodhbir Singh Mehta	Singapore	66	2002	Michael Lee Ham	United States	581
10	Björn Bachmann	Germany	31	1969	Steven B Koenig	United States	529

Figure 5.

Visualization analysis of co-authorship and co-citation. (A) The co-authorship network visualization map of authors related to the field. (B) The co-cited authorship network visualization map of authors related to the field. (C) Active authors in the studies of endothelial keratoplasty.

Furthermore, an investigation of co-citations (Fig. 5B) amongst writers illustrates the enduring influence of foundational publications and well-known figures on academic discourse. Prominent academics like Francis Price Jr., Gerrit Melles, and Marianne O. Price are noteworthy figures who have made significant contributions to the field of endothelial keratoplasty. Author partnerships like those of Terry Ma, Gerrit R. J. Melles, and Francis W. Price Jr. exhibit the cooperative efforts that are propelling progress in this specialized field. Likewise, the collaborative endeavors of writers like Lisanne Ham, Gerrit R J Melles, and Isabel Dapena underscore their pivotal function in clarifying aspects of Descemet’s membrane endothelial keratoplasty within clinical practice.

Additional visualizations (Fig. 5C) present an extensive overview of the authors’ cooperation network and offer considerable insight into the interdependence of scholarly endeavors in this field.

High-cited and co-citation references

Table 5 presents the ranking of the 10 documents with the most citations. The field of research on endothelial keratoplasty is characterized by influential studies that have garnered significant recognition, as indicated by their accumulation of more than 100 citations apiece from 2004 to 2023. Sophie X Deng et al’s paper titled “Descemet Membrane Endothelial Keratoplasty: Safety and Outcomes: A Report by the American Academy of Ophthalmology” is the most frequently referenced among these, accumulating 209 citations. It is closely followed by the paper “Descemet-stripping automated endothelial keratoplasty” with 195 citations. The work titled “Descemet’s Stripping with Endothelial Keratoplasty in 200 Eyes: Early Challenges and Techniques to Enhance Donor Adherence” by Francis W Price Jr et al is ranked third and has garnered 189 citations, indicating its high level of recognition in the academic community. This study is expected to provide useful insights into the safety and results of Descemet Membrane Endothelial Keratoplasty (DMEK), which is a surgical treatment used to treat corneal endothelial dysfunction.

Moreover, Table 6 displays the top 10 references that have the maximum number of co-citations. The most commonly mentioned references in the literature are those produced by Francis W Price Jr et al (418 citations), Mark S Gorovoy et al (400 citations), W Barry Lee et al (371 citations), G R Melles et al (348 citations), and Francis W Price Jr et al (336 citations). In addition, employing sophisticated bibliometric tools like CiteSpace allows for a thorough examination of important references that have received substantial citations. This offers vital insights into the changing research patterns within the literature on endothelial keratoplasty (refer to Fig. 6).

Table 6.

Top 10 highest co-cited papers on endothelial keratoplasty

Rank	Title	Journal	Type	Authors	Year	Citations
1	Descemet’s stripping with endothelial keratoplasty in 200 eyes: Early challenges and techniques to enhance donor adherence	Journal of Cataract & Refractive Surgery	Article	Francis W Price Jr et al	2006	418
2	Descemet’s membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival	Ophthalmology	Article	Mark S. Gorovoy et al	2009	400
3	Descemet’s stripping endothelial keratoplasty: safety and outcomes: A report by the American Academy of Ophthalmology	Ophthalmology	Review	W Barry Lee et al	2009	371
4	A surgical technique for posterior lamellar keratoplasty	Ophthalmology	Article	G R Melles et al	1998	348
5	Descemet’s stripping with endothelial keratoplasty in 50 eyes: A refractive neutral corneal transplant	American Journal of Ophthalmology	Article	Francis W Price Jr et al	2005	336
6	Risk of corneal transplant rejection significantly reduced with Descemet’s membrane endothelial keratoplasty	Ophthalmology	Article	Arundhati Anshu et al	2012	320
7	Descemet’s stripping with endothelial keratoplasty: Comparative outcomes with microkeratome-dissected and manually dissected donor tissue	Ophthalmology	Article	Marianne O Price et al	2006	295
8	Descemet’s membrane endothelial keratoplasty: Prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss	Ophthalmology	Article	Frederico P Guerra et al	2011	280
9	Descemet membrane endothelial keratoplasty versus descemet stripping automated endothelial keratoplasty	Ophthalmology	Article	Theofilos Tourtas et al	2012	273
10	A technique to excise the descemet membrane from a recipient cornea (descemetorhexis)	Cornea	Article	Gerrit R J Melles et al	2004	241

Figure 6.

The visual network of references on EK from 2004 to 2023.

Keyword analysis

Keywords play a crucial role in identifying key areas within a topic and guiding study focus based on their frequency of occurrence. Upon entering all keywords into the VOSviewer node, the terms “Penetrating keratoplasty,” “DMEK,” and “Eyes” were merged. Subsequently, we identified the 20 most significant terms, as depicted in Table 7. Moreover, Fig. 7A illustrates the top 40 terms. “Penetrating keratoplasty,” “DMEK,” “Endothelial keratoplasty,” and “DSAEK” were the most frequently mentioned terms, along with “risk factors” and “outcomes.” Fig. 7A delineates the four primary research directions in EK, delineated by the colors green, blue, yellow, and red.

Table 7.

The top 20 keywords in the studies of endothelial keratoplasty

Rank	Keyword	Occurrences	Total link strength
1	Penetrating keratoplasty	786	2323
2	DMEK	630	1593
3	Eyes	503	1484
4	Endothelial keratoplasty	434	1278
5	DSAEK	403	1152
6	Keratoplasty	290	669
7	Cornea	272	800
8	Corneal transplantation	267	843
9	Posterior lamellar keratoplasty	264	896
10	Transplantation	231	682
11	Risk factors	187	768
12	Tissue	182	586
13	Lamellar keratoplasty	170	555
14	DSEK	161	642
15	Cell loss	157	552
16	Graft-survival	152	565
17	Keratoconus	151	434
18	Survival	150	520
19	Complications	124	436
20	Visual acuity	123	413

Figure 7.

Analysis of keywords related to publications on EK. (A) The co-occurrence network visualization map of keywords related to EK. The keywords were clustered into three groups according to their colors. Large nodes represent keywords with high frequencies. (B) Density visualization for keywords in co-occurrence network map. Each keyword in the density visualization has colors that indicates its appearing frequency. Keywords in yellow emerge more frequently, while green emerge less frequently. (C) Keywords of studies on EK from 2004 to 2023. (D) The top 15 keywords with the strongest citation bursts regarding EK from 2004 to 2023. The red segment of the blue line denotes the burst duration of a keyword.

Keyword bursts, representing terms that emerge abruptly and substantially within a specific time frame, serve as indicators of evolving hotspots. Using CiteSpace, we identified key references in this field with high citation counts (see Fig. 7C). The timeline is depicted as a blue line segmented into years, with detected bursts highlighted in red. Penetrating keratoplasty ranked #1 with the highest burst strength (16.16), followed by visual acuity (13.18), posterior lamellar keratoplasty (51.31), DLEK (25.15), and surgical technique (15.64). Conversely, posterior lamellar keratoplasty and visual acuity exhibited the longest burst duration, indicating that they were research hotspots from 2005 to 2013. Keywords currently undergoing burst phases, such as “thickness” and “quality,” signify their importance as ongoing research hotspots likely to endure in the future.

By employing co-occurrence analysis, a density network map was generated to visually depict the terms (refer to Fig. 7B). Fundamental terms that have emerged in EK research encompass “Penetrating keratoplasty,” “DMEK,” “Endothelial keratoplasty,” and “Outcomes.”

Discussion

Overview

This analysis provides insights into the research trajectory of EK through bibliometric analysis, offering valuable perspectives on thematic evolution, key contributors, and emerging trends. The exponential growth in academic publications and citation related to EK underscores the significance of this topic as a focal point for researchers.

Our analysis reveals that research on EK has attracted global attention, with contributions originating from diverse geographical regions[18]. Globally, EK research has gained significant traction, with notable contributions from countries such as the United States, China, Germany, England, India, and the Netherlands. Notably, the United States emerges as a key player in this field, a phenomenon that may be attributed to its robust healthcare infrastructure and research ecosystem[19]. China, Germany, England, India and Netherlands are also notable contributors, reflecting a high level of interest in EK research worldwide. These global patterns underscore a widespread academic and clinical commitment to EK advancements.

Research institutions

The top institutions in EK research include representatives from both developed and developing countries, underscoring the global engagement in advancing knowledge in this field. Leading research institutions in the United States, such as the Legacy Devers Eye Institute, Johns Hopkins University, Mayo Clinic, and Harvard University, at the forefront of EK research, have demonstrated consistent output and impact. For example, Johns Hopkins University has conducted landmark studies confirming DMEK’s advantages in reducing graft detachment and improving visual acuity[20]. Mayo Clinic has also been pivotal in optimizing donor tissue preparation and storage, enhancing graft viability and patient outcomes[21].

In China, institutions like Sun Yat-sen University’s Zhongshan Ophthalmic Center and Fudan University have made significant contributions[22]. The Zhongshan Ophthalmic Center is renowned for its development of international ophthalmic surgical guidelines and research on post-transplant graft monitoring as mentioned in Chinese expert consensus on keratoprosthesis procedure (2021)[22]. Its comprehensive approach to healthcare, education, and research has substantially supported the improvement of treatment outcomes for ophthalmic patients worldwide.

In India, the Ahmedabad Eye Research Center has emerged as a key player in global ophthalmic research. Their innovative studies on surgical techniques and postoperative care for diverse patient populations provide valuable insights integrated into international guidelines for corneal transplantation. Notably, their adaptations for transplantation in tropical climates have significantly enhanced postoperative recovery for patients in such regions[23].

Collaborative networks, such as the partnerships between the Rotterdam Eye Hospital in Europe and the Singapore National Eye Center in Asia, have been instrumental in facilitating the exchange of knowledge and fostering interdisciplinary synergy. These collaborations significantly advance EK research, particularly through innovations in the utilization of bioengineered corneal tissues. For instance, joint research efforts have led to the development of new bioengineered corneal grafts that improve graft survival rates and reduce rejection incidents[24]. Such international collaborations not only enhance knowledge dissemination but also accelerate the development and clinical application of novel technologies, ultimately benefiting ophthalmic patients worldwide[25].

The significance of these institutions lies in their ability to secure funding, maintain research infrastructure, and attract international expertise. These factors are crucial for conducting cutting-edge research. By leading global collaborations, these institutions enhance the overall quality and impact of EK research, contributing to the development of innovative treatments and improving patient outcomes worldwide.

Influential journals

Journals such as Investigative Ophthalmology & Visual Science (IOVS) and Experimental Eye Research are pivotal for disseminating findings related to EK, playing key roles in shaping and disseminating scholarly discourse. Additionally, Cornea, American Journal of Ophthalmology, and British Journal of Ophthalmology are influential in propagating research findings. These platforms enable researchers to share discoveries, advancing the field significantly.

For example, IOVS focuses on corneal cell biology and regenerative mechanisms, crucial for EK technique improvements[26]. Experimental Eye Research focuses on corneal cell biology and regenerative mechanisms[27]. Cornea publishes groundbreaking studies corneal diseases and transplantation, detailing clinical outcomes and surgical innovations in EK[6]. American Journal of Ophthalmology and British Journal of Ophthalmology include critical reviews and original research articles, highlighting EK advancements^[1,28].

The rigorous peer-review processes of these journals ensure high-quality, reliable research. By facilitating the rapid exchange of ideas, these journals accelerate the translation of research into clinical practice, benefiting patients and healthcare providers. Their high impact factors and citation indices reflect their role in advancing EK research and influencing clinical guidelines and protocols globally[29].

Thematic evolution

The thematic analysis of references elucidates the evolving landscape of research in EK, delineating distinct phases in its progression[30]. From the initial focus on cell differentiation and replacement to the exploration of stem cell-derived neurotrophic factors and induction of human pluripotent stem cells, the trajectory of research in EK reflects a nuanced understanding of corneal biology and therapeutic modalities[31]. In recent years, research has increasingly focused on advanced therapeutic techniques such as gene therapy and nanotechnology, which show great potential in improving the success rates of corneal transplantation and reducing postoperative complications.

In this context, it is crucial to highlight the seminal contributions of key studies to the field of EK. The American Academy of Ophthalmology’s report on DMEK thoroughly reviews its safety and outcomes, establishing DMEK’s efficacy in reducing postoperative complications and enhancing visual recovery, thus shaping clinical practices[32]. Furthermore, the study on descemet-stripping automated endothelial keratoplasty (DSAEK) elaborates on its procedural advancements, highlighting improved endothelial cell survival and visual outcomes. These enhancements have simplified the surgical process and increased success rates[30]. Additionally, the study on Descemet’s stripping with endothelial keratoplasty in 200 eyes addresses early surgical challenges and techniques to enhance donor adherence. This research offers valuable insights and practical solutions that have refined surgical techniques and improved patient outcomes[33].

Recent literature explores gene therapy, biomaterials, and surgical instrumentation, signaling a trend toward more targeted and personalized interventions[1] . Understanding these shifts informs both research agendas and clinical decision-making.

Emerging trends

Collectively, these foundational studies have significantly enhanced the safety, efficacy, and widespread adoption of EK procedures. The evolution of research themes in EK signifies a deeper comprehension of underlying biological processes and the development of more sophisticated therapeutic approaches. This progression highlights the dynamic nature of the field and its responsiveness to emerging scientific discoveries and technological advancements. Understanding these thematic shifts is crucial for identifying future research directions and ensuring continued innovation and improvement in treatment methodologies.

An important development in recent years is the emergence of cell-free therapy as a burgeoning area of investigation[34]. The use of exosomes as therapeutic agents holds promise for overcoming challenges associated with traditional cell-based approaches, such as immune rejection and integration issues[35]. Exosomes can act as mediators of intercellular communication, delivering beneficial signaling molecules to promote tissue repair. The transition towards cell-free therapies underscores a paradigmatic evolution in EK research, signaling a shift towards more refined and clinically viable treatment modalities[36].

Another critical trend in EK research is the focus on the thickness of corneal grafts, particularly in DMEK and DSAEK. Studies have shown that thinner grafts in DMEK can lead to better visual outcomes and faster recovery times compared to thicker grafts used in DSAEK[6]. This focus on graft thickness highlights the continuous efforts to optimize surgical techniques and improve patient outcomes.

The significance of emerging trends such as cell-free therapy lies in their potential to revolutionize the current treatment paradigms. By offering alternative solutions that minimize the risks and complications associated with traditional cell-based therapies, these innovations pave the way for safer, more effective, and more accessible treatments. As research in these areas progresses, it promises to expand the therapeutic toolkit available to clinicians, ultimately improving patient outcomes and quality of life.

Collectively, these trends suggest a broader shift in EK from procedural innovation to biologically guided therapy, integrating molecular insights with clinical execution.

Limitations

Despite significant strides in endothelial keratoplasty research, certain limitations warrant consideration[37]. First, data were retrieved solely from the Web of Science Core Collection (WoSCC)[38], which may omit relevant literature indexed in other databases. Second, citation-based metrics are dynamic and may evolve with time. To enhance the robustness of our analysis, future studies could incorporate various additional indices, such as the Journal Impact Factor, Source Normalized Impact per Paper (SNIP), and SCImago Journal Rank (SJR)[39]. Lastly, the continuous updating of databases could introduce minor inconsistencies, though this is unlikely to affect the overall conclusions.

Conclusion

We are witnessing an explosion of research on EK. The United States emerges as a leading contributor in this field. This bibliometric analysis illustrates the remarkable expansion and transformation of endothelial keratoplasty (EK) research over the past two decades. The United States remains a dominant contributor, supported by a robust research infrastructure and strong international collaborations. Journals such as Cornea and Investigative Ophthalmology & Visual Science serve as critical platforms for disseminating influential findings.

Our findings reveal that the scope of EK research has broadened from immune-mediated conditions to include other pathologies such as glaucoma and retinopathy of prematurity, highlighting EK’s growing relevance in complex ocular disease management. Moreover, emerging research frontiers – including cell-free therapy, graft optimization, and molecular innovations – signal a transition toward biologically informed, precision-based interventions.

Overall, our bibliometric analysis presented here provides a comprehensive overview of research in EK, offering valuable insights into its thematic evolution, key stakeholders, and emerging trends[39]. It provides researchers, clinicians, and policymakers with a comprehensive overview of key themes, institutions, contributors, and future directions in EK. Continued investment in global collaborations, innovative technologies, and translational research will be essential to further elevate the safety, accessibility, and efficacy of EK procedures. Despite barriers and obstacles that may arise, ongoing studies and collaboration are necessary to fully realize the potential of these advancements and further enhance the efficacy and accessibility of EK in clinical practice. By recognizing current advancements and anticipating future needs, the EK research community can move closer to realizing the full clinical potential of this transformative surgical technique. We look forward to embracing a promising and rosy future of clinical and academic research in EK and in ophthalmic fields.

Ethical approval

Ethics approval was not required for this narrative review.

Consent

Informed consent was not required for this narrative review.

Sources of funding

Funding/Support: Supported by the National Natural Science Foundation of China (Youth project, No. 82 101 081 and General project, No. 82 371 023) and Key Research and Development Program of Hubei Province, China (No. 2020BCB055).

Author contributions

S.C.: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Project administration, Writing – review & editing. Y.Y.: Conceptualization, Formal analysis, Methodology, Visualization, Writing – review & editing, Data curation, Investigation, Project administration, Writing – original draft. Z.Y.: Resources, Validation. Y.W.: Resources, Software, Validation. Q.D.: Resources, Validation. J.M.: Resources, Validation. Y.C.: Resources, Validation. J.P.: Resources, Validation. X.S.: Resources, Validation. J.F.: Resources, Validation. Y.W.: Resources, Validation. Y.Y.: Conceptualization, Funding acquisition, Project administration, Supervision.

Conflicts of interest disclosure

The authors indicate no ffnancial support or conflicts of interest.

Guarantor

Yanning Yang.

Research registration unique identifying number (UIN)

None.

Provenance and peer review

None.

Data availability statement

Datasets generated during and analyzed during the current study are publicly available.