Global Research Status Regarding Uveitis in the Last Decade

ABSTRACT Purpose To provide an overview on global uveitis research in the last decade in terms of countries/regions, organizations, scholars, journals, trending topics, and fundings. Methods This cross-sectional bibliometric analysis yielded 10656 uveitis publications in English for subsequent bibliometric analysis. Results In terms of the number of publications, the leading country/region was the USA (3007). The most productive organization was the University College London (420). The most productive research team was Professor Yang’s group (146). A higher h-index was noted in University College London (48). Professor Rosenbaum was the first h-index holder (32). Keywords of interest included topics such as biologics, COVID and OCT. Publications by Ocular Immunology and Inflammation (968) ranked the first position. Conclusions The USA is the leading force in uveitis study. Asian countries/regions, such as China (mainland) and India, are exerting a substantial role worldwide. Trendy topics cover COVID-19, OCTA.

Uveitis is a collection of disorders manifesting as intraocular inflammation and can be caused by multiple etiologies, including immune response, infectious agents, and ocular trauma. 1,2ts underlying mechanisms are extremely complex and not fully understood at this time. 3Fortunately, with the continuous efforts of uveitis experts, the mystery of this disease is gradually being unveiled.We have witnessed an unparalleled development in the field of uveitis in the last decade.For a better performance in the next decade, a scientific question should be answered: where are we now?Herein, we provide an answer by performing a bibliometric analysis of 10656 publications relevant to uveitis from July 1, 2012 to July 1, 2022.
5][6] In order to objectively evaluate the quality of scientific output, multiple bibliometric indicators, including publications (total publication, publication as corresponding author, and publication as first author), citations (total citation and citation per publication), and h-index are presented in this work.Therein, the h-index (a bibliometric indicator widely used worldwide for scientific performance evaluation 7 ) of an individual (or study group) means he (or they) has h publications cited h times or above, 8 and is a recognized reflection of productivity and impact. 9sing the data extracted from the Web of Science Core Collection (WoSCC), we characterized the annual publication growth, leading countries/regions/organizations/scholars/ journals, trending topics and funding information.Overall, this work presents a macroscopic overview regarding the uveitis research status worldwide in the last decades.

Search term confirmation
As the uveitis can be caused by numerous origins and diseases, we constructed 281 search formulas to obtain the uveitis literature as comprehensively as possible (appendix).Search terms contain: "uveitis", main subtypes of uveitis and their synonyms, which were further divided into two parts: types affecting only the eyes (#1) and types involving multiple systems (#2).The second part was additionally characterized by "ALL = (eye) OR ALL = (ocular) OR ALL = (ophthalm*)" (#3).Finally, the retrieval was executed in terms of "#1 OR (#2 AND #3)" via Advanced Search function.

Data analysis and visualization
Publications and citations of each year, the countries/regions, organizations, scholars, journals and funding were acquired from WoSCC.The average growth rate (AGR), compound average growth rate (CAGR), relative growth rate (RGR) and curve fitting were calculated using Microsoft Excel (Software, version 16.57).The 100 top cited publication focusing on the topic of uveitis were sorted from the WoSCC database.It is worthwhile pointing out that some papers focusing primarily on non-uveitis-focused topics rather than uveitis itself were not listed in these top cited papers.This kind of inclusion criterial has been reported previously. 4The titles and keywords of the 100 most highly cited papers were sliced using tm 11 (Package, version 0.7-10) and topicmodels 12

Annual publications and literature characteristic
Our search yielded 10656 uveitis related papers published from July 1, 2012 to July 1, 2022 (Figure 1A), including 8679 articles (81.45%) and 1977 review articles (18.55%) (Figure 1B), among which 379 publications (3.55%) were early access (figure S1).The 100 most cited papers were additionally listed in table S1.Among the top cited publication, the review type ratio (29%) is 10.45% higher than that in general (figure S2).In general, the annual publication number exhibited an upward trend over the past decade.In the last year, the value reached a peak at 1476 publications including 1144 articles and 332 review articles (Figure 1A).This result suggests an increasing attention to uveitis from scholars.In each year, papers in article type consistently accounted for around 80% of the annual publications.
Figure S3 presented the growth rate (GR) per year, entailing an average growth rate (AGR) of 5.00%, a compound average growth rate (CAGR) of 76.19%, a relative growth rate (RGR) of 5.10%, and the fitted curve: y = −0.0001x 5 + 1.252x 4 -5047.4557x 3+ 10174700.1151x 2 − 10255110239.3861x+ 4134458627715.37 (R 2 = 0.8283).The total citation was up to 160018 times over the years, leading to an average citation per publication of 15.02 and a h-index of 116.

Geographical analysis on top 10 contributing countries/ regions
In the last decade, there were a total of 143 countries/regions contributing to the uveitis publications.The top productive ten countries/regions, in descending order, were United States of America (USA), China (mainland), England, Italy, Turkey, India, Japan, Germany, France, and Netherlands.In Figure 2, each circle represents a country/region, and its size indicates the number of papers from this country/region.The thickness of the lines connecting the circles reflects the intensity of cooperation between countries/regions, and the same color indicates relatively closer cooperation.Next to each circle, the total number of publications, the h-index (in square brackets), and the total citation (in angle brackets) from this country/region were marked.Obviously, the USA dominated the chart by contributing 28.22% of world total publications (3007 out of 10656) and 40.65% of world total citation (65040 out of 160018).China (mainland) ran the second position with 1335 publications (12.53% of world total publications) and 16443 citations (10.28% of world total citations).England and Italy were the following two countries/regions with 909 and 794 publications, respectively.As for the total citation, apart from the USA, a higher citation was usually observed in European countries/ regions.In Asia, the highest citations were observed in China (mainland) (16443), followed by Japan (10694) and India (8258).In the context of cooperation, the USA had extensive collaborations with countries/regions over the world, especially with England, Japan, and India, contributing to 42.57% of their publications (1280 out of 3007).The second productive country/region, China (mainland), cooperated mainly with the Netherlands, which was mainly attributed to a long-term and close cooperation between Professor Yang's team and Professor Kijlstra of Maastricht University.In addition, the total link strength is an indicator reflects the collaboration strength of the research forces, which is presented in Table 1 for the top 10 countries/regions.Unsurprisingly, the USA is the most committed country for international cooperation with a total link strength of 1255 (Table 1).
Both quantity (reflecting productivity) and quality (indicating impact) have been considered as measurements of scientific performance.Accordingly, h-index, an indicator that combines the influence of productivity and impact, was also used in this study.The result showed that USA was the leading country/region in terms of h-index hierarchy (95), followed by England (66), Italy (61), France (61), Germany (58), China (mainland) (52) and Netherland (49).

Cooperation network of the top 100 organizations
With respect to the research organization, WoSCC identified 9436 organizations contributing to uveitis publications.The top 100 most productive organizations with more than 48 publications were visualized in figure S4.In the network diagram, each node represents an organization, thicker connection between the nodes implies stronger cooperation, and the shorter distance along with the same node color indicates relatively closer relationship.Apparently, most institutions among the top 100 organizations shared a tight collaborative relationship with each other.
Notably, the most prolific organization was University College London (UCL) (420 publications), followed by Harvard University (341 publications), Johns Hopkins University (260 publications), Chongqing Medical University (217 publications), and Oregon Health and Science University (194 publications).As for citation and h-index, UCL was the organization with the highest citation (9948) and h-index (48) (Table 1).

Leading scholar analysis
Over the past decade, a total of 44251 scholars have contributed to uveitis publications.The bibliometric indicators of the leading ten scholars were quantified in the context of publications (total publications, publications as corresponding author or first author), citations (total citations, citations per publication), total link strength and h-index (figure S5 and Table 1).Furthermore, we illustrated the most productive 100 scholars with VOSviewer software facilitating big data mining and identified the emerging scholars in the last decades (Figure 3).
Notably, Yang, PZ and Rosenbaum, JT were the only two scholars in top 10 position of all these four rankings (i.e., total publications, h-index, publications as corresponding author and first author).Yang, PZ was the most productive scholar with 166 publications (Ranking 1st), including 146 publications published as both corresponding author (Ranking 1st) and first author (Ranking 10th), with a h-index of 27 (Ranking 3rd).Rosenbaum, JT was the highest h-index holder (Ranking 1st) with a total of 102 publications (Ranking 6th), 33 publications as corresponding authors (Ranking 6th) and 20 publications as first authors (Ranking 4th).
As to the collaboration degree of the uveitis scientists, we have used several indicators to examine it.Gupta, V was the most active scholar in collaboration with others with a total link strength of 627 (Table 1).We also presented the co-authorship network map of the top 100 productive scholars with a minimum of 30 publications (Figure 3A).Each node indicates a scholar.The node scale is positively correlated with the number of author publications.Nodes in same color indicates that the scholars are likely from one study group.A thicker link between nodes indicates a tighter cooperation between scholars.Apparently, the thickest link between nodes was observed between the two most productive scholars (Yang, PZ and Kijlstra, A) in the red clusters.Indeed, the long-term and close cooperation between Professor Yang's team and Professor Kijlstra of Maastricht University fostered a strong cooperation between China (mainland) and the Netherlands.The scholar with the highest h-index (Rosenbaum, JT) was found in the blue cluster, along with a number of other USA scholars in the yellow cluster, including Foster, CS, Thorne, JE, and Jabs, DA, maintaining the USA as the leading force in the field of uveitis.Similar results were observed in the Pearson correlation analysis (Figure S6).According to the hclust algorithm, Yang, PZ and Kijlstra, A were in one cluster.Scholars from the USA (i.e., Foster, CS, Thorne, JE and Rosenbaum, JT) tended to be in one cluster, and scholars from India, France and Singapore (i.e., Gupta, V, Bodaghi, B, Agrawal, R, Agarwal, A and Biswas, J) inclined to be in one cluster (Figure S6).The Figure 3B is a time-oriented derivative of the Figure 3A.The closer the node color is to green, the more recent the scholar's average publication time is, and therefore the more likely the scholar is an emerging scholar in the last decade.It was clear that the majority of identified emerging scholars are from Italy, China (mainland), India, and Japan, indicating a rapid development in uveitis study in these countries/regions.

Keywords occurrence network analysis
Keywords, an essential part of a publication, reflect the main topic of the publication.We extracted a total of 14175 keywords from the retrieved data for further analysis of keyword occurrence network.The top 200 keywords with a minimum 25 occurrences were brought into visualization (Figure 4).Larger node sizes are associated with higher keyword occurrences, shorter distances indicate closer relevance, and nodes in the same color represent similarity among topics.
As indicated, the keywords are grouped into 4 major clusters (Figure 4A).The red cluster contained the most items (70 keywords) related to uveitis subtypes such as Behcet's disease (also identified as major topics in the top 100 most cited papers (figure S2B)), Blau syndrome, juvenile idiopathic arthritis, and multiple sclerosis.These subtypes have received more attention in the last decade.Moreover, the uveitis treatment drug study was included in this cluster, as evidenced by keywords like adalimumab, infliximab, and rituximab.The adalimumab and infliximab were also identified as major words in the most cited paper (figure S2B), indicating that uveitis targeted therapeutic biologics have been developed extensively in the last decade.The second major topic was the risk factors of uveitis (green cluster).Evidently, uveitis research related to HIV, cytomegalovirus, herpes simplex virus, cataract, glaucoma, and vitrectomy have been extensively conducted.In the third cluster (blue cluster), inflammation and autoimmunity related topic (e.g., TNF-alpha, IL-17, Th17, oxidative stress, biomarkers) were identified.Lastly, the fourth cluster was colored in yellow, focusing on ocular imaging technology associated keywords, such as optical coherence tomography (OCT), optical coherence tomography angiography (OCTA) and fluorescein angiography.In addition, similar topics (e.g., tomography, imaging, fluoroscopy, and angiography) also frequently appeared in the most cited studies (figure S2C).
While informative, keywords were also analyzed based on average occurrence time (Figure 4B).Keywords marked closer to green suggest that the average year of their occurrences are more recent and thus more likely to be trending topics now.For example, the rapidly evolving OCTA were identified as emerging topics.Undoubtedly, the advances in imaging techniques have significantly facilitated the early identification and characterization of uveitis.COVID-19 and SARS-CoV-2 were also recognized as novel keywords.This is understandable as the coronavirus pandemic has greatly affected various aspects of our life in the last two years.In addition, ocular drug delivery, biomarker, retinal detachment, and hydroxychloroquine were also identified as novel keywords.

Co-citation analysis of journal in the field of uveitis
A co-citation relationship is formed when two journals are cocited in the same publication.The higher the co-citation frequency of the two journals, the more they tend to be in the same academic area.From the 10656 extracted papers, there The total link strength (for the country/region) was analyzed from the top 10 countries using VOSviewer software.* The total link strengths (for the organization and the scholar) were analyzed from the top 100 organization or the top 100 scholar using VOSviewer software.† The calculation of the H-index was based on the literature data collected in this study, and not on all scientific publications of a particular country/region, organization or scholar.In Figure 4A, larger node sizes mean higher keyword occurrences, shorter distances mean closer relevance, and nodes in the same color represent similarity among topics.In Figure 4B, keywords marked closer to green mean that the average year of their occurrences are more recent and thus more likely to be trending topics now.(11300), British Journal of Ophthalmology (11074), JAMA Ophthalmology (Used to be Archives of Ophthalmology) (9793), and Annals of the Rheumatic Diseases (8849).
To assess the quality of journals in the field of uveitis, we listed the leading 10 journal based on the total publications (Table 2).Apparently, the Ocular Immunology and Inflammation published the most papers (968) regarding uveitis, which also allowed it to receive the highest citation (8215) as a whole although its citation per publication was not high (8.49).The British Journal of Ophthalmology and the American Journal of Ophthalmology published the second and third most papers on uveitis (245 and 226, respectively).The Ophthalmology ranked the first position in terms of the h-index (44) (figure S7), followed by Ocular Immunology and Inflammation (34), Retina-The Journal of Retinal and Vitreous Diseases (33), American Journal of Ophthalmology (32), and Autoimmunity Reviews (32).

Funding-supported publication
In the field of uveitis, the top 20 funds contributing to the publications are illustrated in figure S8.It is apparent that a total of 7 funds were from the USA, dominating the rank by taking the first to third, fifth, tenth, and fifteenth, seventeenth positions.China occupied the fourth, twelfth, and twentieth positions, followed by European (6th), Japan (7th and 11st), England (14th and 18th), Brazil (16th).Apart from that, there were four healthcare companies which made a considerable contribution to the publication of uveitis, namely Abbvie (8th), Novartis (9th), Pfizer (13rd), and Roche Holding (19th).

Discussion
In the present study, we built 281 search formulas to retrieve the publications regarding uveitis as comprehensively as possible.Using bibliometric analysis, we qualitatively and quantitatively analyzed the characteristics of countries/regions, organizations, scholars, keywords, journals, and funds from 10656 uveitis publications over the past decade.Collectively, this study provides an overview perspective of uveitis research status over the past decade, thus providing an answer to the scientific question, "Where are we now?".To our knowledge, we are unaware of any previous bibliometric analysis reports on uveitis and could find no reference to it in a computerized search in databases, such as Web of Science, PubMed and Scopus.
Throughout the history of uveitis study, the USA has been the leading academic force.According to the present results, it successfully remained so both in productivity and impact over the last decade.Its achievement was attributable to abundant financial support and the remarkable contributions of a number of scholars, such as Rosenbaum, JT (Oregon Health and Science University), Foster, CS (Harvard Medical School), and Thorne, JE (Johns Hopkins University).European countries/regions, such as England, France, Germany, Italy, and the Netherlands generally had a high academic impact, as reflected by their relatively high citation counts and h-index.Asian countries/regions, such as China (mainland), India, and Japan, have experienced a surge in productivity in the last decade.China (mainland), in particular, was nowhere near the top 10 in terms of productivity a decade ago.Presently, it is the second most productive country/region regarding uveitis publications, second to the USA.This monumental progress was mainly attributing to Professor Yang and his team (Chongqing Medical University) for their ongoing efforts to bring the study of uveitis in China (mainland) to the world.Similarly, A growing number of uveitis scholars such as Professor Gupta and Doctor Agarwal from India are identified as leading or emerging scholars.This proves that the academic strength of Asian researchers is playing a significant role in the field of uveitis.Moreover, international collaborations have clearly stimulated the development of uveitis research, as evidenced by the accomplishment from the USA, China (mainland), and the Netherlands, and therefore more and deeper international collaborations are encouraged. 14t is worthwhile to point that there is still room for Asian countries/regions to improve their academic impact.Productive as they were, their citations and h-index were not yet comparatively high.Behind this possibly lies historical and local forces.One potential reason is that researchers tend to pay more attention to study groups that have maintained authoritative positions for many years, and frequently cite their works in publications.Another point is that in some regions, the quantity of publications is over-weighted in the evaluation of an individual's academic performance. 15That might result in a paper that could be of higher quality being divided into several papers of lower quality. 15In the next decades, we expect their productivity to bring more cuttingedge scientific output.After all, the ultimate goal of conducting uveitis research is to fully understand this complex blind- The calculation of the H-index was based on the literature data collected in this study, and not on all scientific publications of the journals.
leading disease and provide optimized treatments for all those patients in clinical practice, instead of simply adding publication numbers.
As keywords frequently reflect the main topics of the publication, we analyzed their profile in this study.Immune response related to cytokines are undoubtedly one of the major topics in uveitis study due to its inflammatory feature.Multiple cytokines such as TNF-alpha, 16 IL-23, 3 and IL-24 17 were investigated for their association with immune cells, the development of uveitis, and the targeting drugs against them. 3veitis subtypes such as Behcet's disease, blau syndrome, and juvenile idiopathic arthritis were extensively investigated mostly due to the rapid development of specific cytokines targeting biologics such as adalimumab, infliximab, and rituximab used in the treatment of these diseases as well as their associated uveitis.Treatment with novel biologics is likely to remain a hot topic in the coming decade. 18][21][22] Hopefully, the new coronavirus will soon be under control.4][25] In old times, invasive fundus staining was inevitably required to investigate the fundus alterations of uveitis patients.There are now rapid, reliable, non-invasive techniques (e.g., OCTA) of obtaining high-quality fundus images, which also allow us to better understand pathophysiologic change in the retina and choroid. 26,27In the coming decade, more cutting-edge technologies will be expected to be used in the study of uveitis.For example, the rapidly evolving omics technologies allow us to see the relationship between genetics, 28 microbes, 29 cells [30][31][32] and uveitis from a new perspective.
With regard to the journal publishing uveitis studies, the Ocular Immunology and Inflammation published the most uveitis studies, greatly promoting the uveitis knowledge sharing.Although its impact (i.e., citations per publication and h-index) was not yet considerably high, more impactful and high-quality papers are expected to be published in the next decade.The Ophthalmology held the highest h-index and citations per publication (data not shown), suggesting its impact in uveitis field.The American Journal of Ophthalmology was the most frequently appearing journals in the references of uveitis publications, indicating its high popularity and recognition among uveitis scholars.
There are several limitations to this work.Firstly, we analyzed only the publications in WoSCC in English language.There is a possibility that we could exclude some studies published in low-profile journals and some journal not included in WoSCC.Secondly, we included only the publications as types of articles and review articles.Other types of scientific contributions, such as book, meeting abstract, proceeding paper, cannot be defined in this analysis.Thirdly, as with any bibliometric analysis, it is not absolutely guaranteed that all publications concerning uveitis are included in this study.The papers that did not contain any words related to uveitis in the article title, abstract, or keywords were not considered in this study. 33Finally, as there is great difference in contribution of the authors involved in the publication, our study does not exactly evaluate the role of each individual in the studies.Hopefully, more accurate indicators will be used to reasonably evaluate the contribution of each author involved in studies.
Fortunately, uveitis research has developed steadily and significantly over the past decade both in clinical and basic science.With a comprehensive understanding of our current research landscape, it is optimistic that productivity will lead to higher quality scientific output in the coming decade, bringing more impactful discoveries.Lastly, we propose a further question: where will we be?We eagerly await the answer in the next decade.

Disclosure statement
No potential conflict of interest was reported by the authors.

Figure 1 .
Figure 1.(A) The illustration of the publication characteristic from July 1, 2012 to July 1, 2022.(B) The publication access type and the document type distribution.

Figure 2 .
Figure 2. Geographical visualization of the publication and collaboration status of the top 10 contributing countries/regions in uveitis research.Each dot represents a country/region, and its size indicates the number of papers from this country/region.The thickness of the lines connecting the circles reflects the intensity of cooperation between countries/regions, and the same color indicates relatively closer cooperation.The total number of publications, the h-index (in square brackets), and the total citation (in angle brackets) from this country/region were marked next to each circle.
are 19791 referenced journals, among which the top 500 journals were cited at least 117 times and brought into the visualization in Figure5.The size and the color density of label are proportional to citation records in retrieved paper references.Same color is suggestive of similar or cross-linked field.It is clear that the journals were divided into four academic area: ophthalmology journals (red cluster), rheumatology journals (blue cluster), basic research journals (purple cluster), and microbiology journals (green cluster).The American Journal of Ophthalmology was the most referenced journal in the last decade (19652 citations), indicating its recognition and popularity among uveitis scholars.That was followed by Ophthalmology (18762), Investigative Ophthalmology and Visual Science (12308), Ocular Immunology and Inflammation

Figure 3 .
Figure 3. (A) The co-authorship network map of top 100 scholars.(B) The chronological overview of co-authorship network map of top 100 scholars.In Figure3A, each node indicates a scholar.The node scale is positively correlated with the number of author publications.Nodes in same color indicates that the scholars are likely from one study group.A thicker link between nodes indicates a tighter cooperation between scholars.Figure3Bis a time-oriented derivative of the Figure3A, in which the node color closer to green indicates that the average publication time of the scholar is more recent.

Figure 4 .
Figure 4. (A) The occurrences network clustering of top 200 keywords based on different domains.(B) The chronological overview of keywords based on average occurrences year.In Figure4A, larger node sizes mean higher keyword occurrences, shorter distances mean closer relevance, and nodes in the same color represent similarity among topics.In Figure4B, keywords marked closer to green mean that the average year of their occurrences are more recent and thus more likely to be trending topics now.

Figure 5 .
Figure 5. Co-citation density network of the referenced journals.

Table 1 .
Top 10 country/region, organization and scholar based on total publication number.

Table 2 .
Top 10 journals based on total publication number.