Received: 3 August 2023 | Revised: 18 September 2023 | Accepted: 3 October 2023

DOI: 10.1111/jocd.16033

REVIEW ARTICLE

Trends in photodynamic therapy for dermatology in recent

20 years: A scientometric review based on CiteSpace

Fujun Huang MM1 | Qiang Fu PhD2 | Lei Tang MM2 | Mingdan Zhao MM2 |
Mengya Huang PhD2 | Xun Zhou PhD1,2

1
College of Traditional Chinese Medicine,
Chongqing Medical University, Chongqing, Abstract
China
Objective: Analyze the research state and development trend of photodynamic ther-
2
Department of Cosmetic Dermatology,
Chongqing Hospital of Traditional Chinese
apy for dermatology using visual knowledge graphs derived from the Web of Science
Medicine, Chongqing, China Core Collection database.

Correspondence
Methods: The Web of Science Core Collection database was utilized as the search
Xun Zhou, Department of Cosmetic data source for the bibliometric analysis, and the associated articles published be-
Dermatology, Chongqing Hospital of
Traditional Chinese Medicine, Chongqing,
tween January 1, 2000, and December 31, 2022, were obtained using the search
China. terms “photodynamic therapy” and “dermatology”. CiteSpace, VOSviewer, and addi-
Email: [email protected]
tional tools were utilized for bibliometric analysis, and visual knowledge graphs were
Funding information created.
Chongqing City Science and Technology
Plan Project
Results: Eight hundred and thirty two articles were retrieved in total, and 747 were
included following de-duplication and transformation. The country with the great-
est number of publications is the United States; the primary research institution was
University of Copenhagen; and the references with the highest centrality were pri-
marily concerned with the selection of photosensitizers; High frequency keywords
primarily comprised 5 aminolevulinic acid and basal cell carcinoma; and the clustering
graph revealed that all keywords fell into 11 categories.
Conclusion: In numerous areas of dermatology, photodynamic treatment is commonly
employed. Current research focuses on nonneoplastic skin diseases and the choice of
photosensitizers. Nonetheless, its specific mechanism and other applications merit
further investigation.

KEYWORDS
bibliometric analysis, CiteSpace, dermatology, photodynamic treatment, VOSviewer

1 | I NTRO D U C TI O N two basic methods for administering PS. PS accumulates selectively

in the sick tissue during the drug-light interval, followed by exposure
Photodynamic therapy (PDT) is a minimally invasive treatment, to an appropriate wavelength light (often in the red spectrum region,
which has attracted widespread attention as a new treatment λ ≥ 600 nm). Normally, PS itself does not react with biomolecules.
method in recent years. Photosensitiser (PS), light source and oxy- When illumination transfers energy from light to oxygen molecules,
gen are the three main elements of PDT. Local or intravenous are the reactive oxygen species (ROS) are produced, such as singlet oxygen

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

J Cosmet Dermatol. 2023;00:1–12.  wileyonlinelibrary.com/journal/jocd | 1

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2 HUANG et al.

(1O2), superoxide radical (•O2−), hydroxyl radical (•HO), and hydro- the search on different days to eliminate substantive bias. Figure 1B
gen peroxide (H2O2), etc. These cytotoxic photoproducts trigger shows the search process. CiteSpace (5.7.R5) was used to perform
a sequence of metabolic reactions that can cause sick tissue dam- a bibliometric analysis and generate knowledge maps of countries/
age and death.1 PDT is rapidly developing in dermatology, where regions, institutions, journals, authors, keywords, references.
it also has significant efficacy or special value in the treatment of CiteSpace: “Time Slicing” was set from January 2000 to
moderate to severe acne, rosacea, actinic cheilitis (AC) and other December 2022; “Years Per Slice” was set to 1; “Pruning” was set
non-indications. 2–5 to “Pathfinder”; and other parameters were left at their default set-
CiteSpace is a software for tracking and analyzing international tings.6,7 VOSviewer: The threshold was set to maintain 25–50 nodes,
cutting edge research. It is used in various research fields to illus- depending on the circumstance.
trate patterns over time in a discipline or field of knowledge and
track the development of research frontiers.6 VOSviewer is a soft-
ware for constructing and visualizing co-occurrence networks of key 3 | R E S U LT S
terms extracted from a large body of scientific literature. The Web
of Science Core Collection database (WoSCC) is of excellent quality, 3.1 | General analysis
which basically covers high-quality research on PDT treatment of
dermatosis. We searched and included 747 studies (including 537 articles and
Articles about PDT for dermatology published at WoSCC be- 210 reviews). As shown in Figure 2, the number of articles/reviews
tween January 1, 2000, and December 31, 2022, were visually an- has steadily increased over the last 20 years, indicating that PDT re-
alyzed using software such as CiteSpace (5.7.R5) and VOSviewer mains a major interest topic in the field of dermatology.
(1.6.18). The aim is to summarize the scope of application of PDT
in dermatology and its indications, explore the hot spots of PDT re-
search in dermatology, predict the hot spots of future research, and 3.2 | Analysis of countries/regions cooperation
develop more effective and efficient therapeutic regimens.
Over the past 20 years, the included publications have been pub-
lished in 61 countries. The top five countries/regions by publication
2 | M E TH O D S volume: the United States (175 articles), Germany (109 articles),
China (99 articles, Including 10 articles from Taiwan), the United
The source for the study came from WoSCC, and the search strategy Kingdom (71 articles), and Italy (66 articles). Countries density
is shown in Figure 1A. As the database is updated daily, we repeated graph created by the VOSviewer (Figure 3). With its large number

F I G U R E 1 The search strategies and the search process.

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HUANG et al. 3

F I G U R E 2 Chronological distribution of publications from 2000 to 2022.

of publications and high centrality, the United States dominates the means that Rolf-Markus has published at least 62 papers, each of
field. Regarding teamwork, countries collaborate with each other. which has been cited at least 62 times. 8

3.3 | Analysis of institutions, journals, and authors 3.4 | Analysis of references cooperation
cooperation
Generally, in the research field, the more frequently literature is
A total of 1130 institutions, 229 journals, and 3265 authors made mentioned, the greater its influence and authority in the field, and
contributions to the field. In terms of major publishing institu- the greater the reliability of the research results. The higher central-
tions, the University of Copenhagen published the most papers, ity of the cited literature is, the greater its mediating significance in
with 21 articles (Figure 4A). Collaboration between the top 10 in- this field, which is worthy of further study. CiteSpace was used to
stitutions is mostly regional, with international collaboration still create the co-occurrence map of references (Figure 5, the co-cita-
lacking. Within our observation, publications on PDT for dermatol- tion network contained 976 cited references and 3826 links). The
ogy cover a wide range of fields, including basic medicine, clinical top five frequency of cited literature9–13 in Table 1, and the top five
medicine, optics, photoimmunology, and more, of which 34.94% centrality of cited literature14–18 in Table 2.
(261 articles) were published in the 10 journals listed in Figure 4B. “Burstness” was used to detect articles that have attracted a
Among them, 62 articles were published in photodiagnosis and great deal of attention from scientists at various times during the last
photodynamic therapy (5-Year IF = 3.577), accounting for 8.30%, 20 years. The citation burst analysis (Figure 6) shows that “Morton
which was the magazine with the largest number of publications. CA, 2002” 9 earned the highest burst value (16.30) from 2010 to
Szeimies, Rolf-Markus (H-index was 62) was the most prolific au- 2013. This review clearly demonstrates the effectiveness of topical
thor with 11 publications. The h-index is an objective criterion for PDT for actinic keratosis (AK), Bowen's disease, and superficial basal
assessing scientific achievement. For example, the H-index of 62 cell carcinomas (BCCs) of the face and scalp. Areas where PDT is
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4 HUANG et al.

F I G U R E 3 Countries density graph.

potentially beneficial are also noted, including viral warts, acne, pso- and average year of each keyword's contribution to each cluster
riasis, and cutaneous T-cell lymphoma. based on the publication date of each keyword (Figure 9). The name
of each cluster and the keywords included were sorted by frequency,
as shown in Table 6.
3.5 | Analysis of keywords cooperation Using CiteSpace's “Burstness” function, this period suddenly ap-
peared a lot of keywords can be calculated. It can effectively reflect
The co-occurrence map of keywords (Figure 7) was created after the period of the primary study contents and themes and reveal the
using CiteSpace to analyze the 747 included documents. development trend. The top 25 of them are listed in Figure 10, show-
Tables 3–5 summarize the top-ranked keywords in terms of over- ing the duration time and intensity of bursts.
all, indications, and complementary therapies. Where the higher
frequency of the keyword indicates the more attention it is getting
in the field. Centrality is the pivot between articles. The higher the 4 | DISCUSSION
centrality of a node, the more important it is in the field of study (but
some nodes with a centrality of 0 may be a recent hotspot in the field Based on keyword analysis, burst analysis and cluster analysis, we
and are not yet well studied. So just because a node has a centrality have identified the following main research themes of interest.
of 0 does not completely negate the importance of that node).
The cluster graph of keywords (Figure 8, Q = 0.3795 and
S = 0.7361) was obtained by the cluster analysis (Log-Likelihood 4.1 | Selection of photosensitizers
Ratio algorithm, LLR) based on the co-occurrence map of keywords.
In general, Modularity Q (Q) is regarded as a network modularity PDT induces necrosis and/or apoptosis of diseased tissue (tumor
index for evaluating the effectiveness of the cluster. Q > 0.3 indi- cells or other target cells) by generating ROS with photoactivated
cates an effective cluster. Weighted Mean Silhouette (S) is used to PS1,19,20: The diseased tissue selectively absorbs the applied PS.
evaluate cluster homogeneity and is a performance indicator of the Visible light to PS absorption bands is then irradiated to diseased tis-
map's overall structure. S > 0.5 shows a sufficient degree of cluster- sue. The phototoxicity is initiated by the absorption of photons by PS,
ing. S > 0.7 indicates a reasonable cluster.6,7 Calculate the timeline which is then followed by the transfer of energy and/or electrons to
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5

F I G U R E 4 Publishing institutions and journals analysis. (A) Top 10 institutions related to PDT in dermatology research. (B) The number of
|

publications and 5-year impact factor of the top 10 scholarly journal.

HUANG et al.
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6 HUANG et al.

F I G U R E 5 The co-occurrence map of references.

TA B L E 1 The top five references with cited frequency.

Name Author Year Document title Source Citation count

1 Morton CA 2002 Guidelines for topical photodynamic therapy: report of a BRIT J DERMATOL 32
workshop of the British Photodermatology Group
2 Braathen LR 2007 Guidelines on the use of photodynamic therapy for J AM ACAD DERMATOL 28
nonmelanoma skin cancer: an international consensus.
International Society for Photodynamic Therapy in
Dermatology, 2005
3 Morton CA 2008 Guidelines for topical photodynamic therapy: update BRIT J DERMATOL 26
4 Kalka K 2000 Photodynamic therapy in dermatology J AM ACAD DERMATOL 21
5 Babilas P 2006 Guidelines for the management of actinic keratoses - EUR J DERMATOL 20
Developed by the Guideline Subcommittee of the
European Dermatology Forum

triplet oxygen (primarily), resulting in the production of 1O2, O2(1Δg), as photodynamic agents. 21 PDT is often carried out by topically ap-
and/or other ROS, and the subsequent oxidation and degradation of plying PS, particularly 5-aminolevulinic acid (5-ALA) or its ester me-
1
vital biomolecules. Especially short-living O2( Δg) plays a crucial role thyl aminolevulinate (MAL), in dermatological indications. In Europe,
in propagation the initial damage to biomolecules that results in tis- three topical photosensitizers are now approved1: MAL Metvix®,
sue destruction, vascular collapse, and cell death. Nonetheless, PDT 5-ALA Ameluz®, and 5-ALA AlaCare®.
is constrained by the properties of PS, particularly the low quantum
yields of ROS in the target environment. A crucial limiting element
is also the low selectivity of PS, which causes photodynamic dam- 4.2 | Selection of light sources
age to surrounding normal tissues and secondary damage owing to
inflammation. Evidently, the choice of PS is crucial to the effective- The conventional light sources for PDT are red light (wavelength
ness of PDT. Hundreds of PS with tetrapyrrole structures have been 630 ~ 635 nm) and blue light (wavelength approx. 410 nm). The red light
used clinically for PDT, including porphyrin, chlorin, and phthalocya- is mostly used as a light source in Chinese dermatology. Commonly
nine derivatives. Furthermore, methylene blue, Rose Bengal, and used emitters include semiconductor lasers, neon-helium lasers, light-
hypericin have been exploited in therapeutic applications or trials emitting diodes (LED), etc. In addition, daylight, as a compound light,
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HUANG et al. 7

TA B L E 2 | The top five references with the centrality.

Name Author Year Document title Source Centrality

1 Dirschka T 2012 Photodynamic therapy with BF-200 ALA for the treatment of BRIT J DERMATOL 0.40
actinic keratosis: results of a multicentre, randomized, observer-
blind phase III study in comparison with a registered methyl-5-
aminolaevulinate cream and placebo
2 Jang MS 2011 A comparative split-face study of photodynamic therapy with BRIT J DERMATOL 0.27
indocyanine green and indole-3-acetic acid for the treatment of
acne vulgaris
3 Werner RN 2015 Evidence- and consensus-based (S3) Guidelines for the Treatment of J EUR ACAD 0.24
Actinic Keratosis - International League of Dermatological Societies DERMATOL
in cooperation with the European Dermatology Forum - Short
version
4 Sotiriou E 2009 5-Aminolevulininic acid photodynamic therapy treatment for tinea J EUR ACAD 0.22
cruris caused by Trichophyton rubrum: report of 10 cases DERMATOL
5 Sotiriou E 2009 5-Aminolevulinic acid-photodynamic treatment for dermatophytic J EUR ACAD 0.20
tinea pedis of interdigital type: a small clinical study DERMATOL

F I G U R E 6 Detection of top 25 references with the strongest citation bursts.

can also be used as a light source for PDT.22,23 PDT with daylight as the shortcomings of each treatment modality improve clinical effi-
excitation light source is called daylight photodynamic therapy (DL- ciency, and reduce recurrence rates. From Table 5 we can see that
PDT) and is mainly used for the treatment of facial dermatosis such as the treatment regimens that are often combined with PDT tend
Grade I ~ II AK, moderate to severe and severe acne, etc. DL-PDT can to be more invasive operations. Literature report: (1). For cancer-
be a less painful, more convenient and effective option. ous or pre-cancerous lesions such as AK, BBC, etc., the fluores-
cence property of PS can be utilized to detect early cancerous or
pre-cancerous lesions that cannot be observed by the naked eye.
4.3 | PDT combination therapy Therefore, surgery, laser, and cryotherapy are often combined with
PDT. Surgery, laser, and cryotherapy are used to treat lesions vis-
Combining PDT with other therapies (such as conventional drug ible to the naked eye, while PDT is used to treat potential lesions.
therapy, surgery, and other phototherapy) can compensate for the (2). For moderate-to-severe acne, papulopustular rosacea, and
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8 HUANG et al.

F I G U R E 7 The co-occurrence map of keywords.

TA B L E 3 High frequency keywords of PDT for dermatology. TA B L E 4 High frequency keywords of PDT for dermatology
(Indications).
High frequency
Name keywords Frequency Centrality Name High frequency keywords Frequency Centrality

1 5 aminolevulinic acid 113 0.12 1 Basal cell carcinoma 94 0.09

2 Guideline 58 0.07 2 Psoriasis 66 0.09
3 Methyl aminolevulinate 53 0.03 3 Acne vulgari 57 0.10
4 Light 39 0.04 4 Actinic keratosis 52 0.12
5 Protoporphyrin ix 37 0.03 5 Squamous cell carcinoma 47 0.07
6 Apoptosis 22 0.02 6 Nonmelanoma skin cancer 42 0.06
7 Photosensitizer 21 0.02 7 Bowens disease 37 0.04
8 Fluorescence 21 0.03 8 Atopic dermatiti 15 0.02
9 Pain 19 0.01 9 Hidradenitis suppurativa 11 0.01
10 In vivo 17 0.02 10 T cell lymphoma 8 0.01

other inflammatory diseases, PDT can be used to eliminate deep infections, PDT can be used to eliminate potential viruses, fungi,
inflammatory cells by reaching the dermis. Therefore, conven- and bacteria by taking advantage of its wide scope of application
tional treatment is often combined with PDT. Conventional treat- and repeatability. Therefore, surgery, laser, cryotherapy, etc. are
ment is used to control secretion and reduce new occurrences, often combined with PDT. Surgery, laser, and freezing eliminate
and PDT is used to treat deep inflammation to reduce the forma- macroscopic local lesions, while PDT eliminates extensive, occult
tion of acne pits and acne marks. (3). For viral, fungal, and bacterial lesions. 24–30
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HUANG et al. 9

4.4 | Clinical applications disease, moderate to severe and severe acne, rosacea, and photoda-
mage, 23,31–33 etc. There are also numerous reports in the literature
According to the PDT clinical guidelines, it is known that PDT is cur- on the efficacy of PDT in some bacterial infections skin diseases,
rently recommended for the treatment of AK, AC, BCC, Bowen's fungal infections skin diseases, viral infectious skin diseases, scar,
skin amyloidosis, extramammary Paget Disease,34–39 etc. In the fu-
TA B L E 5 High frequency keywords of PDT for dermatology ture, we will try to apply PDT to more refractory diseases and work
(complementary therapies). towards writing more complete clinical guidelines.

High frequency
Name keywords Frequency Centrality
4.5 | Adverse reactions
1 Intense pulsed light 31 0.03
2 Pulsed dye laser 22 0.03
During PDT (approximately 3 ~ 4 weeks), common adverse reac-
3 Cryotherapy 10 0.01
tions to PDT include erythema, oedema, pruritus, pain, and burn-
4 Surgery 7 0.00 ing sensation, etc. In severe cases, oozing, pustules and flaking may
5 Carbon dioxide laser 6 0.00 occur. 23,40 Most patients refuse to use PDT because of its adverse
effects. Thus, the best time for treatment is missed. The search for
more appropriate treatment modalities (such as photosensitizers,
light sources) to reduce the adverse effects of PDT will be the next
research focus and difficulty.

5 | CO N C LU S I O N

This study provides academics with a resource for understanding

the research direction and trend of PDT treatment of dermatosis. It
is important to note, that this study only covered English literature in
WoSCC and lacked relevant Chinese literature, therefore it has some
limitations. In a later phase, domestic and international research
F I G U R E 8 The cluster graph of keywords.

F I G U R E 9 The timeline view of keywords.

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10 HUANG et al.

TA B L E 6 Keywords cluster analysis results of PDT for dermatology.

Cluster S-value Keywords

#0 actinic keratosis 0.705 Aloe, non-melanoma skin cancer, meta-analysis, double blind, safety, adjuvant
radiotherapy, in situ, actinic keratosis quideline, 5 percentimiquimod cream,
5-fluorouracil, cryosurgery
#1 actinic keratosis 0.700 Drug delivery, acne therapeutics, oxygen, liposm, inactivation, laser therapy,
breast cancer, sezary syndrome, alopecia areata, plaque psoriasis, acid
photodynamictherapy, toenail onychomycosis, singlet oxygen
#2 photodynamic therapy 0.740 Bath puva, antimony, 308 nmexcimer laser, barrier function, 311 nm uvb, benign,
ultraviolet, puva, quality of life, narrow band, uvb, topical puva, chronic actinic
dermatiti, adjunct, adverse event, risk, 8-methoxypsoralen
#3 actinic keratosis 0.749 Nanoparticle, tumor, 5 aminolevulinic acid ester, death domain, apoptosis,
protoporphyrin ix accumulation, 20s proteasome, melanoma, caspase-3, lesion,
bronchoscopy, wart, basal cell nevus syndrome
#4 topical photodynamic therapy 0.718 Superficial basal cell carcinoma, 5 years follow up, 5-aminolevulinic acid-
photodynamictherapy, ablative laser, verteporfin, adverse effect, label clinical trial,
absorption spectrum, scalp, 12 month follow up
#5 acne vulgaris 0.665 Bioadhesive patch, topical methyl aminolevulinate, skin neoplasm, acnevulgari, diode
laser, acne grading scale, acid 20 percentcream, lichen sclerosus, medical robot,
androgen metabolism, ala (20% 5-aminolevulinic acid)
#6 hypertrophic scar 0.859 Gold nanoparticle, protoporphyrin, vulvar lichen sclerosus, 5-aminolevulinic acid
photodynamic therapy, lichen sclerosus et atrophicus, Actin, 630 nm laser,
isotretinoin, antibiotic resistant
#7 drug discovery 0.838 Alopecia, transgenic mice, pain, ala-dgme, transdermal delivery, controlled trial, nitric
oxide, betamethasone dipropionate, antiinflammatory activity, atopic dermatiti
#8 autoantibody titer 0.996 Plasmapheresis, extracorporealphotochemotherapy, plasma exchange, antibody titer,
azathioprine, antibody, corticosteroid, adjuvant therapy, disease
#9 bullosa acquisita 0.964 Acquired epidermolysis bullosa, chemotherapy, extracorporeal photochemotherapy,
antigen, anchoring fibril, autoantibody
#10 enhanced sterilization 0.993 Antioxidant property, active constituent, antimalarial activity, aqueous solution,
berberine

F I G U R E 1 0 Detection of top 25
keywords with the strongest citation
bursts.
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HUANG et al. 11

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