Mortality in patients with Dupuytren's disease in the first 5 years after diagnosis: a population-based survival analysis.

Previous studies suggest that Dupuytren's disease is associated with increased mortality, but most studies failed to account for important confounders. In this population-based cohort study, general practitioners' (GP) data were linked to Statistics Netherlands to register all-cause and disease-specific mortality. Patients with Dupuytren's disease were identified using the corresponding diagnosis code and assessing free-text fields from GP consultations. Multiple imputations were performed to estimate missing values of covariates, followed by 1:7 propensity score matching to balance cases with controls on confounding factors. A frailty proportional hazard model was used to compare mortality between both groups. Out of 209,966 individuals, 2561 patients with Dupuytren's disease were identified and matched to at least four controls. After a median follow-up of 5 years, mortality was found to be actually reduced in patients with Dupuytren's disease. There was no difference in mortality secondary to cancer or cardiovascular disease. Future studies with longer average follow-up using longitudinal data should clarify these associations in the longer term.Level of evidence: III.

Treatment durability of limited fasciectomy vs. percutaneous needle fasciotomy for Dupuytren's disease.

BACKGROUND: Patients with Dupuytren's disease (DD) are mostly surgically treated by percutaneous needle fasciotomy (PNF) or limited fasciectomy (LF), but data on time intervals to retreatment is lacking. We aimed to estimate the risk of retreatment within certain time periods after treatment with PNF and LF. METHODS: We used data of participants of a cohort study on the course of DD who were treated only with PNF or LF. Our primary outcome measure was time to retreatment of DD. We included sex, age at first treatment and having a first degree relative with DD as confounders in our analysis. We applied a bivariate gamma frailty model to estimate the risk of retreatment within 1,3,5, 10 and 20 years after treatment with PNF and LF. RESULTS: The time to retreatment was significantly shorter after treatment with PNF than after LF (Wald test 7.56, p<0.001). The estimated 10-year risk of retreatment for men who underwent their first treatment at a younger age and with a first degree relative with DD was 97% after PNF and 32% after LF. The estimated 10-year risk for women who underwent their first treatment at an older age without a first degree relative with DD was 20% after PNF and 6% after LF. CONCLUSIONS: Our results show that the patients treated with PNF have a higher risk of retreatment. The results of this study could contribute to individualized information on the treatment durability in the future, which would improve patient counseling about the expected retreatment needs.

Assessing Facial Palsy: Does Feedback Improve Assessment Using the eFACE and Sunnybrook Facial Grading System?

OBJECTIVE(S): To explore learning effects when applying the clinician-graded electronic facial function scale (eFACE) and the Sunnybrook Facial Grading System (Sunnybrook). METHODS: Surgeons, facial rehabilitation therapists, and medical students were randomly allocated to the eFACE (n = 7) or Sunnybrook (n = 6) and graded 60 videos (Massachusetts Eye and Ear Infirmary open-source standard set); 10 persons with normal facial function and 50 patients with a wide variation of facial palsy severity. Participants received an introduction and individual feedback after each set of 10 videos. Scores were compared to the reference score provided with the set. Multilevel analysis was performed to analyze learning effect. RESULTS: A learning effect was only found for the eFACE, with significant difference scores in set 1 and 2 compared to set 6, and no significant difference scores in the following sets. The difference score was associated with the reference score (severity of facial palsy) for eFACE (ß = -0.19; SE = 0.04; p < 0.001) and Sunnybrook (ß = -0.15; SE = 0.04; p < 0.001). Age of participants was also associated with the difference score in the eFACE group (ß = 0.18; SE = 0.03; p < 0.001). No differences in scores were found between groups of participants. CONCLUSION: The eFACE showed a learning effect of feedback while the Sunnybrook did not. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren's disease.

Dupuytren's disease (DD) is a highly heritable fibrotic disorder of the hand with incompletely understood etiology. A number of genetic loci, including Wnt signaling members, have been previously identified. Our overall aim was to identify novel genetic loci, to prioritize genes within the loci for functional studies, and to assess genetic correlation with associated disorders. We performed a meta-analysis of six DD genome-wide association studies from three European countries and extensive bioinformatic follow-up analyses. Leveraging 11,320 cases and 47,023 controls, we identified 85 genome-wide significant single nucleotide polymorphisms in 56 loci, of which 11 were novel, explaining 13.3-38.1% of disease variance. Gene prioritization implicated the Hedgehog and Notch signaling pathways. We also identified a significant genetic correlation with frozen shoulder. The pathways identified highlight the potential for new therapeutic targets and provide a basis for additional mechanistic studies for a common disorder that can severely impact hand function.

Presence of crown-like structures in breast adipose tissue; differences between healthy controls, BRCA1/2 gene mutation carriers and breast cancer patients.

PURPOSE: Crown-like structures (CLS) in breast adipose tissue are associated with inflammation and a potential factor in breast cancer behaviour. Whether this effect varies between breast cancer subtypes and is influenced by BMI and BRCA mutation status is presently unknown. Therefore, we compared CLS presence between adipose tissue of healthy controls, BRCA1/2 gene mutation carriers and breast cancer patients, and assessed the relation of CLS with clinical outcome in breast cancer patients. METHODS: Immunohistochemical staining for CD68 was performed on breast adipose tissue sections of 48 healthy controls, 78 BRCA1/2 gene mutation carriers and 259 breast cancer patients. CLS presence and index (CLS/cm2) were correlated with BMI, BRCA status, tumour presence, intrinsic tumour subtype and tumour characteristics. Associations with clinical outcome were assessed. RESULTS: CLS were more often present in breast cancer patients compared to BRCA carriers and healthy controls. CLS presence was associated with the presence of breast cancer and high BMI. CLS were more often present in Luminal-B-like tumours compared to the other subtypes. No correlations between CLS and BRCA status or age was found. In TNBC, CLS were related to lymphovascular invasion. No association with survival was found. CONCLUSION: In conclusion, CLS were more frequently present in breast adipose tissue of breast cancer patients compared to BRCA1/2 gene mutation carriers and healthy controls. Furthermore, our study provides evidence of the association between obesity and presence of CLS. The prognostic significance and impact on clinical outcome of differences in CLS numbers should be further assessed in prospective studies.

Polygenic Risk Associations with Clinical Characteristics and Recurrence of Dupuytren Disease.

BACKGROUND: Dupuytren disease (DD) is a common complex trait, with varying severity and incompletely understood cause. Genome-wide association studies (GWAS) have identified risk loci. In this article, we examine whether genetic risk profiles of DD in patients are associated with clinical variation and disease severity and with patient genetic risk profiles of genetically correlated traits, including body mass index (BMI), triglycerides, high-density lipoproteins, type 2 diabetes mellitus, and endophenotypes fasting glucose and glycated hemoglobin. METHODS: The authors used a well-characterized cohort of 1461 DD patients with available phenotypic and genetic data. Phenotype data include age at onset, recurrence, and family history of disease. Polygenic risk scores (PRSs) of DD, BMI, triglycerides, high-density lipoprotein, type 2 diabetes, fasting glucose, and hemoglobin A1c using various significance thresholds were calculated with PRSice using the most recent GWAS summary statistics. Control data from LifeLines were used to determine P value cutoffs for PRS generation explaining most variance. RESULTS: The PRS for DD was significantly associated with a positive family history for DD, age at onset, disease onset before the age of 50, and recurrence. We also found a significant negative correlation between the PRSs for DD and BMI. CONCLUSIONS: Although GWAS studies of DD are designed to identify genetic risk factors distinguishing case/control status, we show that the genetic risk profile for DD also explains part of its clinical variation and disease severity. The PRS may therefore aid in accurate prognostication, choosing initial treatment and in personalized medicine in the future. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Repeated percutaneous needle fasciotomy for recurrent Dupuytren's disease.

Percutaneous needle fasciotomy (PNF) is an attractive option for repeated application for recurrence. We found that extension deficit correction was similar after a first, second and third PNF, though the interval between treatments was longer after a first versus second PNF.

The association between echogenicity and progression of Dupuytren's disease (DD): Birth of an imaging biomarker?

BACKGROUND: The shift of focus towards disease-controlling treatments to prevent DD progression at an early stage underlines the need for objective and reliable measurements that can monitor and predict the course of disease. Ultrasound has been studied as a potential tool for this purpose. This study examined to what extent echogenicity of early DD nodules predicts clinical progression. METHODS: Sonographic assessments of Dupuytren's nodules were performed by the same observer on 151 participants as part of an ongoing prospective cohort study on the course of DD. Echogenicity was assessed by determining the greyness of a nodule relative to the surrounding tissue, using ImageJ software. Progression of disease was defined as 1) an increase in total passive extension deficit (TPED) of ≥15 degrees and 2) surgical intervention of the examined ray, both occurring after the sonographic assessment. The associations between echogenicity and time to progression were estimated using Cox-regression models. RESULTS: The association between echogenicity and time to TPED progression showed that for every additional decrease of 1% in relative greyness (darker image) of a nodule, the risk of TPED progression during follow-up increases by 3.4% (hazard ratio [HR] = 0.966, 95% confidence interval [CI]: 0.935-0.966). Similarly, echogenicity was also associated with time to surgical intervention (HR = 0.967, 95% CI: 0.938-0.997), which indicates a higher risk for surgery during follow-up for darker nodules. CONCLUSIONS: These results suggest that echogenicity is predictive of the prognosis of the early stages of DD and might potentially be used as a prognostic imaging biomarker in the future.

Patient-Perceived Hand Function Can Predict Treatment for Dupuytren Disease.

BACKGROUND: Web-based patient-reported outcome measures (PROMs) could help surgeons remotely assess the need for examination and subsequent treatment of patients with Dupuytren disease (DD). The authors studied whether the Unité Rhumatologique des Affections de la Main (URAM) and the Michigan Hand Questionnaire (MHQ) could predict DD treatment. METHODS: In this prospective cohort study, the authors compared MHQ and URAM scores of treated patients with those of untreated patients. For the treatment group, the authors selected a score closest to 1 year before treatment. For controls, the authors randomly selected a score. The authors also tested the predictive value of a 1-year change score between 15 months and 6 weeks before treatment. The primary outcome measure was DD treatment. The predictive value was determined using the area under the curve (AUC). An AUC greater than 0.70 was considered good predictive ability; 0.70 to 0.50, poor predictive ability; and less than 0.50, no predictive ability. RESULTS: The authors included 141 patients for the MHQ analysis and 145 patients for the URAM analysis. The AUC of the MHQ and URAM scores measured 1 year before treatment were 0.80 (95% CI, 0.71 to 0.88) and 0.75 (95% CI, 0.68 to 0.82), respectively. The 1-year change score resulted in an AUC less than 0.60 for both questionnaires. CONCLUSIONS: The results show that both the MHQ and URAM score measured around 1 year before treatment can predict treatment for DD. If future studies show that telemonitoring of patients with DD with PROMs is also cost-effective, web-based PROMs could optimize patient care and effectiveness of DD treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Prefabricated fibula free flaps in reconstruction of maxillofacial defects: Two cases of transplanting a fractured fibula.

BACKGROUND: The two-staged prefabricated vascularized fibula free flap is used in maxillofacial reconstruction. We describe the possible cause and management of two cases of fibula fracture after implant placement. METHODS: The patients were treated with two-stage reconstruction with a prefabricated vascularized fibula free flap. Six dental implants were placed in both fibulas. Fibula fractures occurred during the osseointegration period before the second procedure. The reconstruction was continued as planned. RESULTS: Both fibulas fractured in the distal segment, possibly due to a thinner cortex more distally. Harvesting of a fractured fibula flap is more difficult than normally due to callus formation and fibrosis. Both transplants became fully functional with extended healing and additional surgery. CONCLUSION: The fracture apparently did not compromise the vascularisation of the fibula and proved still sufficient for successful harvest and transfer of the flap. The patient should be made aware that additional corrective surgery may be indicated.

An economic evaluation of radiotherapy for patients with symptomatic Ledderhose disease.

BACKGROUND: Evidence for effectiveness of radiotherapy for Ledderhose disease was demonstrated in the LedRad-study. However, the health economic impact of Ledderhose disease is unclear. Therefore, an economic evaluation alongside the LedRad-study was planned. METHODS: The economic evaluation was performed as a cost-effectiveness and cost-utility analysis from the societal perspective. Primary outcome parameters were pain burden and Quality Adjusted Life Years (QALY), until 12 months after the end of treatment. Secondary analyses were performed with outcomes until 18 months. Incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) were calculated to express costs per unit improvement in pain burden and costs per QALY gained, for radiotherapy compared to sham-radiotherapy. Bootstrap replication was used to assess uncertainty surrounding the ratios and to construct cost-effectiveness acceptability curves for QALY gain. RESULTS: Previous analysis showed a statistically significant improvement in pain- and QoL scores in favour of radiotherapy at 12 and 18 months. At these timepoints and excluding treatment costs, cumulative total costs were considerably lower in the radiotherapy group. The ICER until 12 months after treatment was 4987 euro per unit of pain burden reduction. The ICUR was 14249 euro per QALY gained. Most of the bootstrap replications were in the upper right quadrant, indicating that health gain can be achieved at higher costs. At increasing levels of willingness to pay for a gain in QALY, the probability of cost-utility gradually increased to approximately 85%. CONCLUSIONS: In patients with symptomatic Ledderhose disease, radiotherapy, at a moderate threshold for willingness to pay, is cost-effective in terms of QoL gain.

Total joint arthroplasty versus trapeziectomy in the treatment of trapeziometacarpal joint arthritis: a randomized controlled trial.

The aim of this double anonymized, randomized controlled trial was to determine whether total joint arthroplasty has superior outcomes than trapeziectomy 1 year after surgery for trapeziometacarpal osteoarthritis. A total of 62 women aged 40 years and older, scheduled for surgery for stage II or III osteoarthritis of the trapeziometacarpal joint, were included and randomized to trapeziectomy or total joint arthroplasty. The primary outcome was the total score of the Michigan Hand Outcomes Questionnaire. Secondary outcomes were the Michigan Hand Outcomes Questionnaire subscale scores, Disability of the Arm, Shoulder and Hand Questionnaire, active range of motion, strength, return to work, patient satisfaction and complications. Data were collected at baseline and at 3 and 12 months. At 1 year, we found no superiority of total joint arthroplasty over trapeziectomy regarding the total score of the Michigan Hand Outcomes Questionnaire. The total joint arthroplasty did show a significant advantage in strength and range of motion.Level of evidence: I.

Radiotherapy for Ledderhose disease: Results of the LedRad-study, a prospective multicentre randomised double-blind phase 3 trial.

BACKGROUND AND PURPOSE: Radiotherapy is considered a treatment option for Ledderhose disease. However, its benefits have never been confirmed in a randomised controlled trial. Therefore, the LedRad-study was conducted. MATERIALS AND METHODS: The LedRad-study is a prospective multicentre randomised double-blind phase three trial. Patients were randomised to sham-radiotherapy (placebo) or radiotherapy. The primary endpoint was pain reduction at 12 months after treatment, measured with the Numeric Rating Scale (NRS). Secondary endpoints were pain reduction at 6 and 18 months after treatment, quality of life (QoL), walking abilities and toxicity. RESULTS: A total of 84 patients were enrolled. At 12 and 18 months, patients in the radiotherapy group had a lower mean pain score compared to patients in the sham-radiotherapy group (2.5 versus 3.6 (p = 0.03) and 2.1 versus 3.4 (p = 0.008), respectively). Pain relief at 12 months was 74% in the radiotherapy group and 56% in the sham-radiotherapy group (p = 0.002). Multilevel testing for QoL scores showed higher QoL scores in the radiotherapy group compared to the sham-radiotherapy group (p < 0.001). Moreover, patients in the radiotherapy group had a higher mean walking speed and step rate with barefoot speed walking (p = 0.02). Erythema, skin dryness, burning sensations and increased pain were the most frequently reported side effects. These side effects were generally graded as mild (95%) and the majority (87%) were resolved at 18 months follow-up. CONCLUSION: Radiotherapy for symptomatic Ledderhose disease is an effective treatment resulting in a significant pain reduction, improvement of QoL scores and bare feet walking abilities, in comparison to sham-radiotherapy.

Short-Term Quality of Life after Autologous Compared with Alloplastic Breast Reconstruction: A Prospective Study.

BACKGROUND: The aim of this prospective multicenter study was to evaluate whether autologous breast reconstruction (BR) leads to lower short-term quality of life (QoL) compared with alloplastic BR, due to the more physically demanding surgery and increased risk of severe complications of autologous BR. METHODS: Changes in QoL after BR were measured in this prospective multicenter study using the BREAST-Q questionnaire, which was administered preoperatively and at 6 weeks and 6 months postoperatively. Characteristics and complications, classified according to Clavien-Dindo, were compared between alloplastic and autologous groups. Profile plots and generalized linear regression models were constructed to analyze the BREAST-Q subscales over time for both BR groups. RESULTS: Preoperatively, women undergoing autologous BR scored lower on all BREAST-Q scales compared with women undergoing alloplastic BR, regardless of whether they underwent immediate or delayed BR. Women undergoing autologous BR scored higher at 6 weeks and 6 months postoperatively on the Satisfaction with Breasts ( P = 0.001), Psychosocial Well-Being ( P = 0.024), and Sexual Well-Being ( P = 0.007) subscales. Postoperative Physical Well-Being: Chest score was similar between the groups ( P = 0.533). Clavien-Dindo grade III or higher complications occurred more often among women in the autologous group (27% versus 12%, P = 0.042). Complications were not associated with worse BREAST-Q scores on any of the subscales. CONCLUSIONS: In contrast to the authors' expectations, and despite the higher incidence of severe complications and lower preoperative breast satisfaction and QoL scores, women undergoing autologous BR had higher levels of breast satisfaction and psychosocial and sexual well-being, both at 6 weeks and 6 months after BR, compared with women undergoing alloplastic BR. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Effect of painful Ledderhose disease on dynamic plantar foot pressure distribution during walking: a case-control study.

BACKGROUND: Plantar pressure distribution during walking in patients with painful Ledderhose disease is unknown. RESEARCH QUESTION: Do patients with painful Ledderhose disease have an altered plantar pressure distribution during walking compared to individuals without foot pathologies? It was hypothesized that plantar pressure is shifted away from the painful nodules. METHODS: Pedobarography data of 41 patients with painful Ledderhose disease (cases, mean age: 54.2 ± 10.4 years) was collected and compared to pedobarography data from 41 individuals without foot pathologies (controls, mean age: 21.7 ± 2.0 years). Peak Pressure (PP), Maximum Mean Pressure (MMP) and Force-Time Integral (FTI) were calculated for eight regions (heel, medial midfoot, lateral midfoot, medial forefoot, central forefoot, lateral forefoot, hallux and other toes) under the soles of the feet. Differences between cases and controls were calculated and analysed by means of linear (mixed models) regression. RESULTS: Proportional differences in PP, MMP and FTI showed increased values for the cases compared to the controls, especially in the heel, hallux and other toes regions, and decreased values in the medial- and lateral midfoot regions. In naïve regression analysis, being a patient was a predictor for increased- and decreased values for PP, MMP and FTI for several regions. When dependencies in the data were taken into account with linear mixed-model regression analysis, the increased- and decreased values for the patients were most prevalent for FTI at the heel, medial midfoot, hallux and other toes regions. SIGNIFICANCE: In patients with painful Ledderhose disease, during walking, a shift of pressure was found towards the proximal and distal foot regions, while offloading the midfoot regions.

Quality of Life 9 to 13 Years after Autologous or Alloplastic Breast Reconstruction: Which Breast Remains Best?

BACKGROUND: The aim of this study was to evaluate the long-term patient satisfaction and quality of life 9 to 13 years after autologous versus alloplastic breast reconstruction and compare the data to those of an earlier study. METHODS: This is a 9-year follow-up study of 92 women who underwent breast reconstruction (47 autologous and 45 alloplastic) between 2006 and 2010 and filled out the BREAST-Q questionnaire in 2010. Changes in BREAST-Q scores were analyzed by using a change score from baseline (2010) to follow-up (2019), which was presented by a mean change score with 95% confidence intervals. Linear regression analyses were performed to test which patient characteristics were related to the BREAST-Q change scores. RESULTS: The response rate at follow-up was 60% (25 autologous and 30 alloplastic). Responders at follow-up had a lower body mass index and had less frequently undergone unilateral breast reconstruction compared to the nonresponders. Women undergoing both autologous and alloplastic breast reconstruction had significantly decreased satisfaction with breasts (-4 points), satisfaction with outcome (-8 points), and satisfaction with nipples (-20 points) over time. None of the patient characteristics, including reconstruction technique, were related to the BREAST-Q change scores. CONCLUSIONS: Satisfaction with breasts, satisfaction with outcome, and satisfaction with nipples decreased slightly over time for women undergoing alloplastic and autologous breast reconstruction. Women undergoing autologous breast reconstruction seemed to remain more satisfied with their breasts 9 to 13 years after breast reconstruction compared to women undergoing alloplastic breast reconstruction. Because of the small sample size, conclusions should be carefully drawn. However, the results were in line with the expectations based on previous literature.

Dupuytren's disease is a work-related disorder: results of a population-based cohort study.

OBJECTIVES: Dupuytren's disease (DD) is a fibroproliferative disorder of the hands, characterised by the development of fibrous nodules and cords that may cause disabling contractures of the fingers. The role of manual work exposure in the aetiology of DD is controversial. We investigated whether current occupational exposure to manual work is associated with DD, and if there is a dose-response relationship. METHODS: In this population-based cohort analysis, we used data from the UK Biobank cohort. Our primary outcome was the presence of DD. The exposure of interest was manual work, measured for each participant in two different ways to allow two independent analyses to be undertaken: (1) the current manual work status of the occupation at the time of recruitment, and (2) a cumulative manual work exposure score, calculated based on the occupational history. We performed propensity score matching and applied a logistic regression model. RESULTS: We included 196 265 participants for the current manual work analysis, and 96 563 participants for the dose-response analysis. Participants whose current occupation usually/always involved manual work were more often affected with DD than participants whose occupation sometimes/never involved manual work (OR 1.29, 95% CI 1.12 to 1.49, p<0.001). There was a positive dose-response relationship between cumulative manual work exposure score and DD. Each increment in cumulative work exposure score increased the odds by 17% (OR 1.17, 95% CI 1.08 to 1.27, p<0.001). CONCLUSIONS: Manual work exposure is a risk factor for DD, with a clear dose-response relationship. Physicians treating patients should recognise DD as a work-related disorder and inform patients accordingly.

Verteporfin ameliorates fibrotic aspects of Dupuytren's disease nodular fibroblasts irrespective the activation state of the cells.

Dupuytren's disease is a chronic, progressive fibroproliferative condition of the hand fascia which results in digital contraction. So far, treatments do not directly interfere with the (myo)fibroblasts that are responsible for the formation of the collagen-rich cords and its contraction. Here we investigated whether verteporfin (VP) is able to inhibit the activation and subsequent differentiation of DD nodular fibroblasts into myofibroblasts. Fibroblasts were isolated from nodules of 7 Dupuytren patients. Cells are treated (1) for 48 h with 5 ng/ml transforming growth factor ß1 (TGF-ß1) followed by 48 h with/without 250 nM VP in the absence of TGF-ß1, or treated (2) for 48 h with TGF-ß1 followed by 48 h with/without VP in the presence of TGF-ß1. mRNA levels were measured by means of Real-Time PCR, and proteins were visualized by means of Western blotting and/or immunofluorescence. Quantitative data were statistically analyzed with GraphPad Prism using the paired t-test. We found that fibroblasts activated for 48 h with TGF-ß1 show a decrease in mRNA levels of COL1A1, COL3A1, COL4A1, PLOD2, FN1EDA, CCN2 and SERPINE1 when exposed for another 48 h with VP, whereas no decrease is seen for ACTA2, YAP1, SMAD2 and SMAD3 mRNA levels. Cells exposed for an additional 48 h with TGF-ß1, but now in the presence of VP, are not further activated anymore, whereas in the absence of VP the cells continue to differentiate into myofibroblasts. Collagen type I, fibronectin-extra domain A, α-smooth muscle actin, YAP1, Smad2 and Smad3 protein levels were attenuated by both VP treatments. We conclude that VP has strong anti-fibrotic properties: it is able to halt the differentiation of fibroblasts into myofibroblasts, and is also able to reverse the activation status of fibroblasts. The decreased protein levels of YAP1, Smad2 and Smad3 in the presence of VP explain in part the strong anti-fibrotic properties of VP. Verteporfin is clinically used as a photosensitizer for photodynamic therapy to eliminate abnormal blood vessels in the eye to attenuate macular degeneration. The antifibrotic properties of VP do not rely on photo-activation, as we used the molecule in its non-photoinduced state.