Global trends and prospects in research of artificial cornea over past 20 years: a bibliometric and visualized analysis

Many studies have been focused on the area of the artificial cornea. In our study, a bibliometric analysis was performed on the artificial cornea to identify the global key research fields and trends over the past 20 years. Publications about artificial cornea were retrieved and downloaded from the Web of Science Core Collection from 2002 to 2021. CiteSpace and VOSviewer were used to analyze countries, institutions, authors, and related research areas. A total of 829 eligible publications were analyzed. The USA was the most productive country for the artificial cornea, followed by China and Canada. Harvard University was the most prolific institution in this field. Cornea published most of the studies in this area and Dohlman CH was the most cited author. Bibliometric analysis in our study first provides a general perspective on the artificial cornea, which can be helpful to further explore the issues in the rapidly developing area.


Introduction
Corneal diseases contribute significantly to blindness worldwide, accounting for 12% of total global blindness [1,2]. Primary corneal transplantation has high rates of graft survival in non-complex eyes [3]. Graft survival decreases in eyes requiring repeat transplantation and complex eyes despite advances in surgical techniques such as selective lamellar keratoplasty [3]. Cornea transplantation in eyes with recurrent and chronic inflammation of the ocular surface, glaucoma, and cornea vascularization is most likely to fail. The availability of cornea tissue varies globally dependent on donor supply and the need for adequate processing facilities [4]. Hence, the development of an "artificial cornea" (keratoprosthesis, KPro) can be considered for end-stage corneal diseases (multiple graft failures or inflammatory ocular surface disease) or as primary treatment to surmount these problems [5,6].
A keratoprosthesis is an artificial or prosthetic cornea made of synthetic materials to restore the vision of patients with severe corneal diseases [7,8]. Pellier de Quengsy first proposed the idea of keratoprosthesis in 1779 with a gradual introduction of various Bibliometric analysis is a standard method that uses mathematical and statistical approaches to exploit bibliometric theory. It is widely used to analyze pertinent literature in various research areas [15]. For instance, a global bibliometric analysis of corneal transplants was performed by Pekel et al. to present the publication trends of the past decade [16]. However, a global bibliometric analysis of artificial cornea has not yet been conducted. Our study was designed to provide an overview of global artificial cornea research based on WoSCC data from 2002 to 2021. Bibliometric analysis was applied to generate the research focus, frontiers, and critical publications of artificial cornea combined with citation information to offer a comprehensive and promising reference for related researchers.

Data source and search strategies
WoSCC provided by Thomson Reuters (Philadelphia, PA, USA) is the most extensive database available and is regarded as the best database for bibliometric analysis [17]. The literature was extracted from WoSCC for the period from 2002 to 2021. The following terms were searched as follows: TS = ("artificial cornea" OR "artificial corneas" OR keratoprosthesis OR kPro OR kPros OR "bioartificial cornea" OR "bioartificial corneas" OR "cornea, bioartificial" OR "corneas, bioartificial"). Only articles and reviews will be included. The language was not restricted as the English abstracts were available. Our study did not directly contact any individual participants, thus ethical approval was not necessary.

Data collection and extraction
Following the above-mentioned search strategies, all data including titles, authors, abstracts, keywords, journals, and cited references were downloaded in "plain text" format and stored in "download_txt" format. We retrieved 1181 publications. All searches were carried out within one day (on 18 August 17, 2022) to avoid prejudice related to database updates. Two investigators (Y.C. and J.Z.) independently performed the research and discussed the controversial publications. The discussion continued until the investigators reached 100% agreement [18]. The information on journal impact factor (IF) and disciplinary category quartiles (Q1-Q4) was obtained from the Journal Citation Report (JCR) (Clarivate Analytics, Philadelphia, United States). The h-index measures the citation impact of individual research results [19].

Bibliometric analysis
Microsoft Excel 2021 (Microsoft Corporation, Redmond, WA, USA) and the bibliometrix package in R 4.2.1 were used for the analysis of bibliometric indicators including annual counts of publications/citations, top-cited publications, countries/regions, institutions, journals, and authors, as well as keywords. CiteSpace V (version 5.8 R3) [20], VOSviewer (version 1.6.18) [21] and the online bibliometric website (https:// bibli ometr ic. com/ app) were used for bibliometric analysis and data visualizations. Different colors in the network visualization represent various groupings, including nations, authors, and institutions, while connecting lines represent factors such as cooperation and citation. The diameter of the circle indicates how strong the association is. The degree of collaboration is shown by the coarseness of the connecting lines [22][23][24]. The cluster network's Q value indicated the network's modularity. The network's cluster performs better the higher the Q value. When Q > 0.3, the network cluster structure was noteworthy. The homogeneity of a cluster network is gaged using the silhouette value. The homogeneity of the cluster network increased as the silhouette value approached 1. The results of the cluster analysis demonstrated good reliability when the silhouette value was greater than 0.7 [25].

Results
Flowchart for searching In total, 829 articles published in the past 20 years were included through our search strategy. Over 99% of these articles were published in English. Most of the publications were original research articles (732,

Countries and institute distribution
The articles we collected were from 64 different countries/regions (Fig. 2b). We ranked the top 10 most highly outputs countries/regions in Table 1. The USA had the most articles published (381, 46.0%), followed by China (84, 10.1%) and Canada (80, 9.7%). Figure 2a reveals the annual trends of publications of the five most high-cited countries/regions. Total citations of all the countries/regions were 17,812 times. Articles from the USA were cited by 8387 times, accounting for 47.1% of all the citations, followed by Canada (1768, 9.9%) and China (1339, 7.5%) (Fig. 3b). Among the collaboration between countries/regions ( Fig. 2c) and the percentage of   (Fig. 3a), we found many countries actively cooperating with other countries, including the USA, Canada and the UK. The most cooperation was between the USA and Canada. Researchers from China, Japan and India were lower active in collaboration with other countries. Figure 2d shows a country/region co-authorship produced by VOSviewer. Out of the 25 countries/regions with at least 8 articles used to generate the co-authorship network, the USA was the most influential country/ region with a total link strength (TLS) is 189, followed by the UK (TLS = 61) and Brazil (TLS = 45). In our study, 890 institutions contributed to the publications we included. The 69 institutions with a minimum of 5 documents were demonstrated in Fig. 3c. Harvard University in the USA holds the most publications, followed by University of Illinois in the USA and L V Prasad Eye Institute in India. We ranked in the top 10 most prolific institutions in this research field in Table 2. Seven institutions are from the USA, two in Singapore, and the other in India. From Fig. 3d, the most prolific institutions published main articles from 2012 to 2016. Figure 4b shows the institution collaboration network, the most collaborative organization is Singapore National Eye Center, followed by Singapore Eye Research Institution and Harvard University.

Journals and articles distribution
All the publications were from 189 different journals in the past 20 years. We have comprehensively ranked the features of the 10 most prolific journals collectively in Table 3. The journals published 378 articles, accounting for 45.6% of all the publications. Cornea was the most productive journal of all (164, 19.8%). This was followed by the American Journal of Ophthalmology (37,4.5%) and the British Journal of Ophthalmology (36, 4.3%). All these journals were categorized into ophthalmology apart from the Biomaterials. Articles from Cornea were the most cited, with citations 3554 times, followed by Ophthalmology (1848) and American Journal of Ophthalmology (966). Ophthalmology ranked first in the number of citations per publication (61.6), followed by Biomaterials (54.1). The dualmap overlay of journals in Fig. 4c was performed by CiteSpace. The citing journal graphs are in the left cluster, while the cited journal graphs are in the right. The lines on the left and right are citation links [26]. We found that most articles were published in journals of neurology, sports and ophthalmology, and these journals mainly cited journals of chemistry/materials/physics, molecular/biology/ genetics and ophthalmology.
The first 10 most cited articles are listed in Table 4. The citations of the paper written by Zebra BL in 2006 were 260 times, ranking the first. Of all the 10 articles, only one was a review article, as the others were all research articles. Eight of the articles were written by American scholars while the other authors were from Canada and China, respectively. Most of the articles were published in ophthalmologic journals with articles published in materials journals.    Authors and co-authors distribution Over 2,900 authors made contributions to the publications included in our study. We identified the 10 most productive authors in the artificial cornea area including h-index, citations, countries and publications (Table 5). Scientists from the USA contribute an enormous of articles to this field. Dohlman CH was the most active author, with 70 articles, followed by Chodosh J (57) and Harissa-Dagher M (42). In terms of citations in this area, the first author was the same as the most productive. Dohlman CH ranked first with 1206 times and followed by Aldave AJ (608) and Harissa-Dagher M, with 529 times. The collaborations between authors are presented in Fig. 4b.   Analysis of keywords THE core word extractions provided by scholars in the studies are keywords. According to the treemap of the most frequent 20 author keywords (Fig. 5a), the top five keywords with a significant number of occurrences are outcomes that appear 147 times; complications 117 times; implantation 89 times; penetrating keratoplasty 88 times and surgery 85 times. The burst keywords through CiteSpace were explored and 20 keywords with the strongest strength of the last 20 years were identified (Fig. 5b). We used CiteSpace to perform a subject clustering map (Fig. 5d) and timeline (Fig. 5c). The articles on the artificial cornea field published from 2002 to 2021 could be categorized into 10 main research hotspots, each of different sizes and periods. The modularity Q value was 0.7394 and the average silhouette value was 0.8919, demonstrating that clustering quality was acceptable. The first 10 clusters were generalized and ordered from the largest to the smallest number of co-cited references. The first cluster was "#0 long-term outcome", and this was followed by "#1 corneal epithelial cell migration" and "#2 anterior segment". The top 20 keywords with the most vigorous citation burst are shown in Fig. 4b. The earliest and highest strength burst keyword in the past 20 years was "artificial cornea", which was from 2002 to 2010. The keywords appeared at different time points and periods, with the highest intensity of the words being "retention" in recent years. As shown in the timeline view, a cluster called "#2 anterior segment" appeared in recent years. The cluster "#0 long-term outcome", "#5 Boston keratoprosthesis type" and "#7 corneal regeneration" were present throughout.

Discussion
In this study, we conducted a bibliometric and visualized analysis of the last 20 years of WoSCC-based SCI artificial cornea. We provide insight into artificial cornea for SCI and some valuable information.
The quantity of publications in each period can indicate the trends in an area of a study. In our analysis, the number of documents published has increased rapidly since 2008 and reached its peak in recent years. Although common artificial corneas such as B-kPro and OOKP had been developed before 2000, their original techniques were refined and standardized later [13,27]. This might be related to the high increase rate of the number of publications since 2008. Currently, this research field remains a hot topic both in ophthalmology and the materials field. Researchers and institutes from the USA were the core study strength with about 46.0% of all publications. In addition, publications from the USA were the highest cited as well. All of these results indicate that the USA leading the quality of articles, institutions, and journals in this field. This result follows a similar trend to many bibliometric studies in other areas, which confirms the USA as an international research leader in both quantity and quality [28][29][30]. China and Canada jointly contributed to the dominant number of publications. However, countries with higher economic rankings were reported to have more and higher qualitative biomedical publications [31]. Of the top prolific countries/regions in our study, countries from other developing areas such as China and India made both noticeable contributions to the artificial cornea field. The academic cooperation network shows that regions such as the USA, Germany and Australia were active in interactions with other regions. However, Asian countries like China, Japan and India were lower active in cooperating with others even though the production was high in these countries. These regions should actively cooperate with others in this field as a higher academic level can be approached by a collaboration of countries and institutions. In addition, the highest TLS was the USA, followed by the UK and Brazil. This demonstrates that contents, originality, usefulness and new contributions of the research may be more closely tied to the citations received than the number of publications.
Regarding institutions, Harvard University was the most prolific of all the institutions. The top 10 most productive institutions were from the USA, India and Singapore. Although most productive countries including China and Canada, their institutions could not get into the most prolific institutions. This might be related to the researchers and institutions that were quite scattered in these countries in the artificial field.
Analyzing journals could help scholars to choose appropriate journals for their paper submission. Journals in the ophthalmology field contributed the most to the artificial area. The journal "Cornea" ranked the first productive journal, with the highest h-index.
Authors generally tend to choose high IF journals for their research publication, and journals with high IF are also interested in publishing high quality papers [32]. All of the top 10 most productive journals had an IF > 3.0. and six of them had an IF > 5.0. The number of citations per article was significantly high in Ophthalmology and Biomaterials. The journals were the only two journals in which IF was over 10. This indicates that the articles in the high IF journals obtain, on average, a more significant number of citations.
Time has an essential effect on articles' citations as the citations of articles accumulate depending on the publication time. While it may take 15 years or more for an article to reach its peak total citations [33], three articles have been published in less than 15 years among the top 5 highest cited articles [34][35][36]. The citations of these articles might continue to increase over the coming years. Of the top 10 cited articles, 60% of these were about the Boston type I keratoprosthesis [34,35,[37][38][39][40], as the Boston type I keratoprosthesis is the most commonly used synthetic cornea worldwide [5,34]. Three articles are found in research on biomaterials of cornea [36,41,42], which is an essential aspect in the artificial cornea field. The other was about OOKP [13], which is one of the most widely used keratoprosthesis worldwide [43]. However, of these articles only one article was review and the other articles were all research articles, which is different from that reported in the previous study [44]. The review written by Ruberti JW et al. was published in 2011 and is one of the top 10 most recently cited articles. The citations of it may increase in future years [42]. The reason for the few highly cited reviews in our study might be that most review articles were published in recent years. Old published papers are expected to have more citations than recent ones [45]. In addition, articles received more citations than reviews in ophthalmologic journals [46]. There is a lack of high-impact publications in this area, as the most cited article has only 226 citations.
Regarding authors, Dolhman CH from Harvard University was one of the leading research and development staff [47]. He ranked first in productivity, publication citations and h-index. Chodosh J was the second most productive author at the same institution as Dolhman CH. Of the most influential authors, seven authors were from the USA, and the other authors were from Canada and Singapore. This is consistent with the result for the most productive countries/regions. This may indicate that the number of active authors is usually higher in fertile countries/ regions. In addition, the collaboration result illustrates close and comprehensive cooperation among scholars all over the world, which indicates have been extensive developments within this field.
Burst keywords can reveal a large amount of attention from experts in a particular area over an extended period of time [48]. They have always been considered another significant indicator of research frontiers. In our study, burst detection showed that "retention," "tissue" and "intraocular pressure" were the new hotspots within the field of the artificial cornea. They were comparing the burst keywords "artificial cornea," "keratoprosthesis" and "adhesion" the last time. The result suggests a shift in focus from the surgery of the artificial cornea to improve prognosis and reduce complications. From the cluster and timeline maps, we found that "long-term outcome," "Boston keratoprosthesis type" and "corneal regeneration" remained all the time during the 20 years. Therefore, these topics might sustain over time, although new hotpots may arise. The cluster "anterior segment" did not emerge until 2007. This is related to increasing attention on permitting keratoprosthesis by using the anterior segment imaging [49,50]. The conventional clinical examination techniques for implanted keratoprosthesis remained with several limitations. Anterior segment imaging, such as ultrasound biomicroscope (UBM) and anterior segment optical coherence tomography (AS-OCT), improves the assessment of anterior chamber structures with poor vision after implantation of artificial corneas [51]. In addition, the most frequently occurring keywords were "outcome" and "complications" in the treemap. This is consistent with the burst keywords and timeline map in recent years. All these observations demonstrate improved outcomes and decreased complications after implanting the artificial cornea is a critical hotspot in this field recently.

Limitations
Our study data only included the literature data in WoSCC without other databases like Scopus and Google Scholar. Additionally, the citation data were only from the articles published from 2002 to 2021, rather than including all the publications in this research area. These issues probably contributed to a selection bias in this study.

Conclusions
In summary, we depicted the scientific output of artificial cornea overall by bibliometric analysis over the past 20 years. Our results reveal that the USA ranked first in terms of productivity, but Asian and European countries also made outstanding contributions. Among all the journals, Cornea has published the maximum number of articles and received the most citations in this field. It seems that the prospects for artificial corneas appear to be even brighter for corneal implantation surgery. We expect that future studies in this area will continue improving the outcomes and reducing complications after implanting the artificial cornea.
Author contributions YC, JZ and WZ contributed to the design of the study. YC and JZ collected and excluded the data. XX and BH performed the statistical analysis. YC wrote the draft of the manuscript. WZ revised the article. All authors critically reviewed the manuscript and approved the final version.
Funding This study was supported by the National Natural Science Foundation of China (81160119) and the Key Research and Development Program in Guangxi (AB20238003).

Data availability
The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Competing interests
The authors declare no competing interests.