This is the first study to report the bibliometric analysis and visualized results of research on MGD. The results of the present study provided a general view of the research progress and trends related to MGD over the last decade.
3.1 Worldwide tendencies in MGD research.
As shown in Fig. 1a, the numbers of publications in MGD research showed progressive and continuous increases from 2011 to 2020, indicating increasing concerns and interests in this area. Among the top 10 most cited publications, seven were related to international workshops on MGD. In the last decade, many countries and institutions increasingly focused on MGD. Among the intricate country network map, the USA showed the highest number of publications and centrality, suggesting that this country is the international collaborative center for MGD research. In the organization analysis, Keio University had the highest number of publications, which reflected its contribution to MGD research. Of the top 10 organizations shown in Table 3, the top three were Keio University (Japan), Yonsei University (Korea), and the University of Louisville (USA). Determining the contributing countries and organizations may help researchers find appropriate collaborations for further study and accelerate the study of MGD. In addition, the journal analysis, which identified the top 10 journals, plays a role in illustrating the importance of a journal and helping ophthalmologists and researchers in MGD research to choose appropriate journals.
The results showed that thousands of scientists were dedicated to MGD research globally; among these 2,559 authors, VOSviewer revealed 21 with 10 or more publications. Authors with the same or similar research directions and subjects were classified into the same groups. Three main clusters and research areas were observed. Determining the leading authors and their research areas in MGD is important for researchers and ophthalmologists to find further cooperative studies.
3.2 Research hotspots.
Keywords, which were simple words, played an important role in identifying the most vital information from publications, as assessed based on the frequencies of the keywords. Both keywords and their occurrences reflect research hotspots. The keyword co-occurrence analysis identified four clusters and research hotpots, as discussed below.
Cluster 1 represented the pathogenesis or potential etiology of MGD based on the keywords “inflammation,” “gene expression,” “contact lens wear,” “fatty acids,” “Sjogren’s syndrome,” “tear osmolarity,” “versus-host-disease” and “androgen deficiency”. Consistent with previous studies, the keywords extracted in cluster 1 were the potential etiologies of MGD, including (1) inflammation/bacteria [8, 9, 30], in which increased levels of phospholipase A2, which is needed for the synthesis of inflammatory mediators, were observed in patients with MGD. Some inflammatory cytokines may cause keratinization of the meibomian gland opening. In addition, the number of commensal bacterial species increased and lipases produced by bacteria could dissolve the lipid secreted by the meibomian gland. (2) Desiccating stress, defined as an external stress and characterized by dry conditions, including “contact lens wear,” “Sjogren’s syndrome,” and “versus-host-disease,” which may influence the differentiation and renewal of meibocytes and lead to MGD. (3) Hyperkeratinization: many factors, including inflammatory cytokines and androgen deficiency, can cause the keratinization of ducts and lead to the obstruction of the meibomian gland. Accompanied by duct hyperkeratinization, inspissated lipid secretions can develop, and ultimately the meibomian glands drop out. (4)Variations in meibum composition/increased meibum viscosity[24, 33]: the proper composition and ratio of meibum ensure its normal flow. Changes in meibum composition alter meibum viscosity and tear osmolarity, leading to meibum accumulation and tear film instability. (5) Others: dyslipidemia, Demodex infestation, and oxidative stress are also involved in MGD. Thus, the keywords in Cluster 1 mainly reflected the different causes of MGD.
Cluster 2 represented MGD diagnosis. The keywords “meibography,” “lipid layer thickness,” “tear film stability,” and “dry eye symptoms” were extracted. There remains no single gold standard diagnosis for MGD. Moreover, it is difficult to distinguish patients with MGD from those with dry eye disease (DED) based on symptoms, as the conditions share similar symptoms such as eye irritation and other ocular surface discomforts. Therefore, careful slit-lamp examination and comprehensive clinical tests are required. While abnormal lid morphology and obstructed meibomian orifices can be evaluated directly in ophthalmologist examinations, new diagnostic tools such as meibography, in vivo confocal microscopy (IVCM), and optical coherence tomography (OCT) have been widely used to assess meibomian glands.
Cluster 3 represented MGD therapy and the International Workshop`s dedication to MGD. Patients with MGD are treated according to the symptoms and their severity. For patients with mild symptoms, publicity related to MGD was meaningful for symptom relief. However, a corresponding treatment is required for patients with more severe clinical symptoms. Regarding the potential etiology of MGD, the corresponding treatment measures are as follows (1) Basic treatments: basic treatments such as eyelid warming, massage, and hygiene are essential. (2) Antibiotics and anti-inflammatory agents: Evidence showed that both antibiotics and anti-inflammatories effectively relieve symptoms in patients with MGD. (3) Lubricants/ artificial tears: Since MGD is the most common cause of evaporative dry eye disease, treatments used for dry eye, including lubricants and artificial tears, are also suitable for MGD. (4) Autologous serum-based eyedrops: Recent studies have suggested that autologous serum-based eye drops may be effective in severe conditions or those accompanied by corneal epithelial damage. However, the safety, accessibility, and cost of these eyedrops require further investigation. (5) Intense pulsed light (IPL) therapy[40, 41]: Recent studies have demonstrated the role of IPL in decreasing telangiectatic blood vessels, Demodex, and antiinflammation. (6) Nutritional supplementation, such as essential fatty acid supplementation, vitamin D3 analog ointment, diquafosol instillation, and intraductal meibomian gland probing have also been proposed. The keywords contained in cluster 3 are also related to the MGD International Workshop, which was held in 2011 and attended by many ophthalmic professors, covering almost all areas of MGD. At that time, many scientists made remarks on topics ranging from basic research to clinical concerns, such as MGD physiology, anatomy, pathophysiology, epidemiology, definition, diagnosis, classification, and treatment, which promoted the development of research on this disease. This is consistent with the growth trend of MGD-related studies in the years after 2011.
Cluster 4 revealed MGD epidemiology, with extracted keywords including “prevalence,” “epidemiology,” “population” and “risk factors.” The growing concern regarding MGD has also emphasized its prevalence. A recent study reported an MGD prevalence of 35.8%. Furthermore, according to Craig et al, the symptoms of MGD occurred earlier within the natural history of disorder progression, even in patients in their 20s, indicating the broad negative effects of MGD. In addition, East Asian ethnicities were more liable to develop MGD, which likely explained our observation of the USA and Keio University in Japan as the country and research institution with the highest levels of contributions to the field, respectively. A recent cross-sectional study reported risk factors for MGD including East Asian ethnicity, age, thyroid disease, oral contraceptive therapy, and migraine headaches. In general, MGD has a high prevalence and is prone to affect the population with these risk factors.