High-Performance Photodynamic Therapy of Tongue Squamous Cell Carcinoma with Multifunctional Nano-Verteporfin.

Background: The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare. Methods: Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites. Results: The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites. Conclusion: The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.

Verteporfin induces lipid peroxidation and ferroptosis in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) has extremely poor prognosis, with a 5-year survival rate of approximately 11 %. Yes-associated protein (YAP) is a major downstream effector of the Hippo-YAP pathway and plays a pivotal role in regulation of cell proliferation and organ regeneration and tumorigenesis. Activation of YAP signaling has been associated with PDAC progression and drug resistance. Verteporfin (VP) is a photosensitizer used for photodynamic therapy and previous work showed that it can function as a YAP inhibitor. The efficacy of VP on human cancer are being tested in several trials. In this study, we examined the effect of VP on reactive oxygen species (ROS) and lipid peroxidation in pancreatic cancer cells, by using fluorescent molecular probes and by measuring the levels of malondialdehyde, a metabolic byproduct and marker of lipid peroxidation. We found that VP causes rapid increase of both overall ROS and lipid peroxide levels, independent of light activation. These effects were not dependent on YAP, as knockdown of YAP did not cause ROS or lipid peroxidation or enhance VP-induced ROS production. Temoporfin, another photodynamic drug, did not show similar activities. In addition, VP treatment led to loss of cell membrane integrity and reduction of viability. Notably, the activity of VP to induce lipid peroxidation was neutralized by ferroptosis inhibitors ferrostatin-1 or liproxstatin-1. VP treatment also reduced the levels of glutathione peroxidase 4 (GPX4), an enzyme that protects against lipid peroxidation. These results indicate that VP can induce lipid peroxidation and ferroptosis in the absence of light activation. Our findings reveal a novel mechanism by which VP inhibits tumor growth and provide insights into development of new therapeutic strategies for the treatment of pancreatic cancer.

Half-dose photodynamic therapy versus 577 nm subthreshold pulse laser therapy in treatment-naive patients with central serous chorioretinopathy.

BACKGROUND: To compare real-life anatomical and functional outcomes of half-dose photodynamic therapy (HD-PDT) and 577 nm subthreshold pulse laser therapy (SPL) in treatment-naïve patients with central serous chorioretinopathy (CSC). METHODS: We retrospectively reviewed consecutive treatment-naïve CSC patients with non-resolving subretinal fluid (SRF) for more than 2 months who received either HD-PDT or SPL treatment. One repetition of the same treatment was allowed in patients with persistent SRF after first treatment. Functional and anatomical outcomes were assessed after first treatment and at final visit. RESULTS: We included 95 patients (HD-PDT group, n = 49; SPL group, n = 46). Complete resolution of SRF after a single treatment was observed in 42.9% of HD-PDT-treated patients (n = 21; median time to resolution 7.1 weeks) and in 41.3% of SPL-treated patients (n = 19; median time to resolution 7.0 weeks). In the HD-PDT-group, 44.9% of patients (n = 22) and in the SPL-group, 43.5% (n = 20) of patients, received a second treatment due to persistent SRF, while 12.2% (n = 6) and 15.2% (n = 7), respectively, opted against a second treatment despite persistent SRF. After the final treatment, complete SRF resolution was observed in 61.2% of all HD-PDT-treated patients (n = 30; median time to resolution 8.8 weeks) and 60.9% of all SPL-treated patients (n = 28; median time to resolution 13.7 weeks, p = 0.876). In the final visit, both groups showed significant improvement of BCVA in comparison to baseline (p < 0.001 for all). The change in BCVA from baseline to final visit was similar for the two groups (HD-PDT, median BCVA change 0.10 logMAR (IQR: 0.0-0.2); in SPL group, median BCVA change 0.10 logMAR (IQR: 0.0-0.2), P = 0.344). The CSC subclassification (simple versus complex) had no influence on the anatomical or functional outcome. CONCLUSIONS: High-density 577 nm SPL resulted in as good anatomical and functional treatment as HD-PDT and may thus represent a treatment alternative to HD-PDT in CSC.

Verteporfin regulates corneal neovascularization through inhibition of YAP protein activation.

Corneal neovascularization (CNV) is a vision-threatening disease that is becoming a growing public health concern. While Yes-associated protein (YAP) plays a critical role in neovascular disease and allow for the sprouting angiogenesis. Verteporfin (VP) is a classical inhibitor of the YAP-TEAD complex, which is used for clinical treatment of neovascular macular degeneration through photodynamic therapy. The purpose of this study is to explore the effect of verteporfin (VP) on the inhibition of CNV and its potential mechanism. Rat CNV model were established by suturing in the central cornea and randomly divided into three groups (control, CNV and VP group). Neovascularization was observed by slit lamp to extend along the corneal limbus to the suture line. RNA-sequencing was used to reveal the related pathways on the CNV and the results revealed the vasculature development process and genes related with angiogenesis in CNV. In CNV group, we detected the nuclear translocation of YAP and the expression of CD31 in corneal neovascular endothelial cells through immunofluorescence. After the application of VP, the proliferation, migration and the tube formation of HUVECs were significantly inhibited. Furthermore, VP showed the CNV inhibition by tail vein injection without photoactivation. Then we found that the expression of phosphorylated YAP significantly decreased, and its downstream target protein connective tissue growth factor (CTGF) increased in the CNV group, while the expression was just opposite in other groups. Besides, both the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and cofilin significantly increased in CNV group, and decreased after VP treatment. Therefore, we conclude that Verteporfin could significantly inhibited the CNV without photoactivation by regulating the activation of YAP.

Seven-year outcomes of combined treatment of anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy; according to polypoidal lesion regression.

PURPOSE: To evaluate the long-term prognosis of polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (anti-VEGF) combined with verteporfin photodynamic therapy (PDT), according to polypoidal lesion regression. METHODS: This study retrospectively reviewed the data of 33 naïve eyes with PCV treated with anti-VEGF combined with verteporfin PDT and followed-up for at least 7 years. The collected data included demographic profile, best-corrected visual acuity (BCVA), central foveal thickness (CFT), PED volume, and presence of submacular hemorrhage. Regression of polypoidal lesion was determined using indocyanine green angiography and optical coherence tomography. All eyes were divided into regression or persistent groups, based on the polypoidal lesion regression one year after the initial combined treatment. RESULTS: BCVA improvement was maintained for 3 years in the regression (p = 0.001) and 1 year in the persistent (p = 0.006) groups, respectively. The mean BCVA of the regression group was better than that of the persistent group over 7 years, but the difference was significant only at 1 year (p = 0.037). The number of eyes which maintained BCVA less than or equal to 0.3 logMAR at 7 years was 11 eyes (64.7%) in regression group and 4 eyes (25.0%) in persistent group (p = 0.022). CONCLUSIONS: Regression of the polypoidal lesion at 1 year after the initial combination treatment was associated with favorable long-term visual prognosis, particularly in terms of maintaining good visual acuity.

Nano-Photosensitizer Directed Targeted Phototherapy Effective Against Oral Cancer in Animal Model.

Background: Photodynamic therapy (PDT) has emerged as a promising strategy for oral cancer treatment. Verteporfin is a powerful photosensitizer and widely used in the treatment of macular degeneration. However, rare work has reported its potential in the treatment of oral cancer. Methods: In this study, we introduce an innovative approach of nano-photosensitizer based on Verteporfin, which was prepared by utilizing macrophage membrane to coat Verteporfin-loaded zeolitic imidazolate framework 8 (ZIF-8) for effective photodynamic therapy against oral cancer. Nanoparticle characteristics were assessed including size, zeta potential, and PDI. Cellular uptake studies were conducted using CAL-27 cells. Furthermore, inhibitory effects in both in vitro and in vivo settings were observed, ensuring biosafety. Assessment of anticancer efficacy involved tumor volume measurement, histological analyses, and immunohistochemical staining. Results: In vitro experiments indicated that the nano-photosensitizer showed efficient cellular uptake in the oral cancer cells. Upon the laser irradiation, the nano-photosensitizer induced the generation of reactive oxygen species (ROS), leading to cancer cell apoptosis. The in vivo experiments indicated that the coating with cell membranes enhanced the circulation time of nano-photosensitizer. Moreover, the specificity of the nano-photosensitizer to the cancer cells was also improved by the cell membrane-camouflaged structure in the tumor-bearing mouse model, which inhibited the tumor growth significantly by the photodynamic effect in the presence of laser irradiation. Conclusion: Overall, our findings demonstrate the potential of macrophage membrane-coated ZIF-8-based nanoparticles loaded with Verteporfin for effective photodynamic therapy in oral cancer treatment. This nano-system holds promise for synergistic cancer therapy by combining the cytotoxic effects of PDT with the activation of the immune system, providing a novel therapeutic strategy for combating cancer.

Combination of verteporfin-photodynamic therapy with 5-aza-2'-deoxycytidine enhances the anti-tumour immune response in triple negative breast cancer.

Introduction: Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2'-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood. Methods: The present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients. Results: Functional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease. Discussion: To our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects.

Examining the efficacy of verteporfin photo-dynamic therapy (PDT) at different dose & fluence levels.

OBJECTIVES: Photodynamic therapy (PDT) is a vaso-occlusive treatment for a number of chorioretinal vascular pathologies. We aimed to retrospectively analyse efficiency and safety of PDT for different conditions (central serous retinopathy (CSR), age-related macular degeneration (AMD), macular telangiectasia type 2 and choroidal hemangioma) and with different verteporfin parameters. METHODS: Clinical parameters were ascertained from the medical records of patients undergoing PDT over a 6-year period. This included indications for PDT, dosing regimens of verteporfin PDT (which includes treatment dose of verteporfin and fluence). Response to treatment was measured by best corrected visual acuity (BCVA) and central foveal thickness (CFT) on ocular coherence tomography. Complications and side effects were recorded. RESULTS: 67.4 % (31/46) of PDT treatments performed over the last six years were for CSR. In the CSR cohort, there were significant improvements in BCVA (0.47 ± 0.24 to 0.29 ± 0.27, p < 0.05) and CFT (350.2µm ± 66.9 µm to 286.1µm ± 60.6 µm. In the AMD cohort, there was no change in BCVA (1.08 ± 0.52 to 1.07 ± 0.53, p = 0.96) but significant improvement in CFT (488.2µm ± 164.6 µm to 348.7µm ± 65.7 µm, p < 0.05). There was no significant difference in BCVA or CFT for macular telangiectasia type 2 and choroidal hemangioma. CONCLUSIONS: PDT continues to have a role in the management of medical retina conditions. Our results show PDT is most effective in improving and stabilizing visual acuity in CSR, with earlier intervention resulting in better outcomes.

Verteporfin Suppresses YAP-Induced Glycolysis in Breast Cancer Cells.

OBJECTIVE: The inhibition of the Hippo pathway through targeting the Yes-associated protein (YAP) presents a novel and promising approach for treating tumors. However, the efficacy of YAP inhibitors in the context of breast cancer (BC) remains incompletely understood. Here, we aimed to investigate the involvement of YAP in BC's metabolic reprogramming and reveal the potential underlying mechanisms. To this end, we assessed the function of verteporfin (VP), a YAP-TEAD complex inhibitor, on the glycolytic activity of BC cells. METHODS: We evaluated the expression of YAP by utilizing immunohistochemistry (IHC) in BC patients who have undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) prior to biopsy/surgery. We employed RNA immunoprecipitation (RIP) and fluorescent in situ hybridization (FISH) assays to assess the interaction between YAP mRNA and human antigen R (HuR) in BC cells. The biological importance of YAP in the metabolism and malignancy of BC was evaluated in vitro. Finally, the effect of VP on glycolysis was determined by using 18F-FDG uptake, glucose consumption, and lactate production assays. RESULTS: Our studies revealed that high expression of YAP was positively correlated with the maximum uptake value (SUVmax) determined by 18F-FDG PET/CT imaging in BC samples. Inhibition of YAP activity suppressed glycolysis in BC. The mechanism underlying this phenomenon could be the binding of YAP to HuR, which promotes glycolysis in BC cells. Treatment with VP effectively suppressed glycolysis induced by YAP overexpression in BC cells. CONCLUSION: VP exhibited anti-glycolytic effect on BC cells, indicating its therapeutic value as an FDA-approved drug.

Red Light-Triggered Anti-Angiogenic and Photodynamic Combination Therapy of Age-Related Macular Degeneration.

Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently, anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) agents has become the standard treatment for wAMD, while it is still subject to several limitations, including the safety concerns of monthly intravitreal administration and insufficient efficacy for neovascular occlusion. Combined therapy with photodynamic therapy (PDT) and anti-angiogenic agents has emerged as a novel treatment paradigm. Herein, a novel and less-invasive approach is reported to achieve anti-angiogenic and photodynamic combination therapy of wAMD by intravenous administration of a photoactivatable nanosystem (Di-DAS-VER NPs). The nanosystem is self-assembled by reactive oxygen species (ROS)-sensitive dasatinib (DAS) prodrug and photosensitizer verteporfin (VER). After red-light irradiation to the diseased eyes, intraocular release of anti-angiogenic DAS is observed, together with selective neo-vessels occlusion by VER-generated ROS. Notably, Di-DAS-VER NPs demonstrates promising therapeutic efficacy against CNV with minimized systemic toxicity. The study enables an efficient intravenous wAMD therapy by integrating a photoactivation process with combinational therapeutics into one simple nanosystem.

Early versus delayed photodynamic therapy for chronic central serous chorioretinopathy.

PURPOSE: Central serous chorioretinopathy (CSCR) patients are sometimes referred to Photodynamic Therapy (PDT) with very long-term disease. The purpose of this study was to analyze the results of PDT in CSCR eyes with long-standing disease. METHODS: The medical records of the patients that underwent PDT for CSCR between 2009 and 2019 were reviewed. Cases were divided into two groups based on the duration of disease before PDT treatment: early treatment (3 to 6 months) and delayed treatment (longer than 6 months). The treatment was defined as successful when the subfoveal fluid was absorbed during follow-up. RESULTS: The PDT treatment was successful in 76% and 77% of eyes in the early and delayed treatment groups, respectively. Both groups showed significant improvement in central retina measurements at the 3-months follow-up which persisted to the last follow-up visit. The visual acuity (VA) at baseline was significantly worse in the delayed treatment group (0.5 ± 0.26 vs. 0.3 ± 0.24, P = 0.042) and improved in both groups but remained low in the delayed treatment group during the study. CONCLUSION: We suggest that if CSCR is not spontaneously improving over 3 months the patient should be offered PDT, to prevent VA loss from the long-term presence of subretinal fluid in the macula. PDT is not associated with loss of vision in eyes with chronic CSCR, and can be safely used in eyes with relatively good VA.

Extensive reduction in choroidal thickness after photodynamic therapy in eyes with central serous chorioretinopathy.

We examined the effect of reduced fluence (rf)-photodynamic therapy (PDT) of the macular area on the wide-field choroidal thickness in 20 eyes with central serous chorioretinopathy (CSC) and 20 age- and sex-matched control eyes. The choroidal thickness at the posterior pole was measured before and after rf-PDT, using a grid with inner and outer rings, each divided into superotemporal, inferotemporal, superonasal, and inferonasal quadrants, respectively, making up a total of nine subfields including the central 3 mm ring. Before treatment, all eyes showed wide-field choroidal thickening from the dilated vortex vein ampulla to the fovea, along the course of the vein. After rf-PDT of the macular area, the choroidal thickness significantly decreased, not only in the irradiated macular area but also outside the arcade vessels in all quadrants (p < 0.001 for all inner subfields; p = 0.035 and p = 0.024 for the outer superonasal and inferonasal subfields, respectively; p < 0.001 and p = 0.004 for the outer superotemporal and inferotemporal subfields, respectively). For control eyes, the choroidal thickness did not differ between the initial visit and follow-up 1.2 ± 0.7 months after the initial visit (p > 0.05 for all subfields). These findings provide new insights into the pathogenesis of CSC and explain the reasons for the effectiveness of rf-PDT for this condition.

Evaluation of the changes in choroidal macular anastomoses after photodynamic therapy and in the follow-up of central serous chorioretinopathy by en face optical coherence tomography.

PURPOSE: To evaluate the changes in the choroidal macular anastomoses after photodynamic therapy (PDT) and in the follow-up of patients with central serous chorioretinopathy (CSCR) by en face optical coherence tomography (EF-OCT). METHODS: Prospective study using EF-OCT images of patients with chronic CSCR treated by PDT with a minimum follow-up of 12 months and with the presence of at least two prominent anastomoses in the macula. Scans of 6 × 6 mm and 12 × 12 mm were made to assess the changes in choroidal macular anastomoses (defined as a diameter ≥150 µm) crossing the medial raphe. EF-OCT was performed before PDT and 3 days, 3 months and at the end of the follow-up after PDT. RESULTS: The mean follow-up time was 23.6 ± 12.1 months. The mean number of anastomoses was 2.5 ± 1.1 in the baseline examination, being 2.3 ± 1.2 in the final examination, with no differences being observed (p = 0.110). A sub-analysis was performed to assess differences in the evolution of the anastomoses between active chronic CSCR and those in which the subretinal fluid (SRF) had been resolved, with no differences being observed in the number or caliber of anastomoses (p = 0.642 and p = 0.306). A significant decrease in the size of anastomoses was found at the 3-day (p<0.01) and 3-month (p = 0.032) visits, but not at the last follow-up visit (p = 0.156). CONCLUSIONS: There was an early decrease in the size of the major macular choroidal anastomotic vessels after PDT treatment. Long-term studies are required to assess its evolution and its possible role in the etiopathogenesis of this disease.

Characteristics Related to Visual Acuity Loss After Successful Photodynamic Therapy for Eyes With Central Serous Chorioretinopathy.

PURPOSE: This study aimed to examine baseline characteristics for identifying factors associated with vision loss (VL) in patients with central serous chorioretinopathy (CSC) who successfully responded to photodynamic therapy (PDT). DESIGN: A retrospective, clinical case-control study. METHODS: This study included 85 eyes with CSC, which underwent PDT, and resolved serous retinal detachment. These eyes were classified into 2 groups: the VL group (best-corrected visual acuity 6 months after PDT was worse than that at baseline) and the vision maintenance or improved group (the others). Baseline factors were analyzed to determine the characteristics of the VL group and assess the diagnostic potential of these factors. RESULT: Seventeen eyes were included in the VL group. The mean values of the neurosensory retinal (NSR) thickness, the internal limiting membrane-external limiting membrane thickness (IET), and the external limiting membrane-photoreceptor outer segment thickness (EOT) in the VL group were significantly thinner than those in the vision maintenance or improved group (NSR thickness, 123.2 ± 39.7 µm vs 166.3 ± 49.6 µm, P < .001; IET, 63.1 ± 17.0 µm vs 88.0 ± 25.4 µm, P < .001; EOT, 60.1 ± 28.6 µm vs 78.3 ± 33.1, P = .041). The sensitivity, specificity, and positive and negative predictive values for predicting VL were 94.1%, 50.0%, 32.0%, and 97.1% for NSR thickness; 94.1%, 51.5%, 32.7%, and 97.2% for IET; and 94.1%, 30.9%, 25.4%, and 95.5% for EOT, respectively. CONCLUSIONS: Pretreatment sensory retinal layer thickness could predict VL after PDT for CSC and may be a helpful reference for PDT.

SINGLE-SESSION BILATERAL REDUCED-SETTINGS PHOTODYNAMIC THERAPY FOR BILATERAL CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: We performed a multicenter, retrospective study on patients with bilateral chronic central serous chorioretinopathy (cCSC) who received single-session bilateral reduced-settings photodynamic therapy (ssbPDT) and assessed anatomical (resolution of subretinal fluid [SRF]) and functional (best-corrected visual acuity [BCVA]) outcomes and safety. METHODS: Patients who underwent ssbPDT between 01/01/2011 and 30/09/2022 were included. The resolution of SRF at first, second, and final follow-up was assessed on optical coherence tomography (OCT), and BCVA measurements were collected at these visits. When fovea-involving ssbPDT was performed, ellipsoid zone (EZ) and external limiting membrane (ELM) integrity was graded before and after treatment. RESULTS: Fifty-five patients were included in this study. Sixty-two of hundred and eight eyes (56%) showed a complete resolution of SRF at the first follow-up, which increased to 73/110 (66%) at the final follow-up. The mean logMAR BCVA improved by -0.047 ( P = 0.02) over follow-up. EZ integrity increased from 14/21 (67%) to 24/30 (80%) while ELM integrity increased from 22/30 (73%) to 29/30 (97%). CONCLUSION: Patients with cCSC with bilateral SRF at baseline showed significant anatomical and functional improvements after ssbPDT, both at short-term and long-term follow-up. No relevant adverse events were noted.

A Photodynamic Therapy Index for Central Serous Chorioretinopathy to Predict Visual Prognosis Using Pretreatment Factors.

PURPOSE: This study aimed to establish a treatment index based on functional outcomes of photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). DESIGN: A retrospective clinical case-control study. METHODS: This was a single-institute study. Eighty (80) eyes with CSC, who were treated by PDT and whose subretinal fluid resolves within 6 months were divided into two groups: those with poor visual outcome (PVO) (best-corrected visual acuity [BCVA] ≤ 0.5 6 months post-PDT), and the remaining eyes (better visual outcome [BVO]). The areas under the curve (AUC) and cutoff values from receiver operating characteristic curves were examined. These was used to predict the groups using pretreatment BCVA and the thickness of each retinochoroidal layer. RESULT: Twenty-one (21) eyes were in the PVO group and 59 eyes in the BVO group were included. The AUCs were 0.959 for BCVA, 0.959 for the thickness from the internal limiting membrane to the external limiting membrane (IET), 0.820 for the thickness from the external limiting membrane to the photoreceptor outer segment layer, 0.715 for the subfoveal retinal thickness, and 0.515 for the subfoveal choroidal thickness. The BCVA and IET cut-off values were 0.267 logMAR and 71.5 µm, respectively. Using the combination of the cutoff values of BCVA and IET, the highest values for the sensitivity, specificity, positive predictive value, and negative predictive value were 95.2%, 94.9%, 85.0%, and 98.0%, respectively. CONCLUSION: The combination of pre-PDT BCVA and IET in CSC can accurately predict the post-treatment visual prognosis. These values could be used as a treatment index of PDT for CSC.

Factors related to changes in visual symptoms after successful photodynamic therapy in central serous chorioretinopathy.

To investigate biomarkers related to visual symptom and best corrected visual acuity (BCVA) improvement after photodynamic therapy (PDT) for central serous chorioretinopathy. This retrospective cross-sectional study involved 42 consecutive eyes, from 42 patients who underwent successful PDT, divided into two groups according to improvement in subjective visual complaints: complete (20 eyes) and incomplete recovery (22 eyes). The clinical characteristics of each group, including central foveal thickness (CFT), foveal avascular zone (FAZ) area, and degree of change in signal voiding of the choriocapillaris on optical coherence tomography angiography, were compared. Correlations between best-corrected visual acuity (BCVA) and baseline clinical features were investigated. At baseline, CFT and FAZ areas showed significant differences between the two groups (all p < 0.05). Multiple binary logistic regression analysis revealed that greater CFT predicted complete recovery from visual complaints (p = 0.002). Reduction or disappearance of signal voiding in the choriocapillaris 6 months post-PDT occurred more frequently in the complete recovery group (p < 0.05). FAZ area before PDT correlated with BCVA before and 6 months after PDT and BCVA improvement during the study period (all p < 0.05). CFT and FAZ area before PDT correlated with completeness of visual symptom recovery after PDT. Smaller FAZ area before PDT correlated with better BCVA before and after treatment.

Hippo/YAP1 inhibition by verteporfin attenuates osteophyte formation in a mouse surgical osteoarthritis model.

Osteophyte is an outgrowth of cartilage formed at the margins of the affected joint through endochondral ossification-like processes, and is one of the most common radiographic features of osteoarthritis (OA) that has been used to define the stage of disease. Osteophyte has been regarded to adapt the joint to the altered biomechanics of OA patients, limits joint movement and represent a source of joint pain, however, the mechanism of osteophyte formation, the morphology characteristics and biomechanical properties of osteophyte cells are remained unclear. In the present study, we isolated osteophyte cells and chondrocytes from late-stage OA patients who underwent total knee replacement surgeries, by applying Atomic Force Microscopy (AFM), we identified osteophyte cells were in irregular shape with dendrites, shrunk cell body, smooth surface and high elastic modulus (23.3 ± 5.4 kPa) when compared with chondrocytes (6.5 ± 1.8 kPa). In addition, osteophyte cells showed higher proliferation ability and colony formation capacity than chondrocytes. Mechanistically, we identified YAP1, the core transcriptional factor of Hippo signaling pathway, was highly expressed in osteophyte cell both at protein and RNA levels. Inactivation of Hippo/YAP1 signaling pathway by Verteporfin is sufficient to inhibit osteophyte cell proliferation in vitro and attenuate osteophyte formation in vivo. In conclusion, the morphology characteristic and biomechanical property of osteophyte cells at single cell level are quite different from chondrocytes, although we could not exclude other regulatory mechanisms, our findings suggested that Hippo/YAP1 is of great importance for osteophyte formation.

[Photodynamic therapy in Germany-Quo vadis?] / Photodynamische Therapie in Deutschland ­ Quo vadis?

BACKGROUND: Photodynamic therapy (PDT) was originally approved for the treatment of neovascular age-related macular degeneration (nAMD) and secondary choroidal neovascularization in myopia (mCNV). In addition, it is used as an off-label treatment in patients with choroidal hemangioma, polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC). OBJECTIVE: To track the development of PDT treatment numbers in Germany between 2006 and 2021 and to investigate the composition of the therapeutic indications. METHODS: In this retrospective study the quality reports of German hospitals were evaluated in the period from 2006 to 2019 and the number of PDTs performed was recorded. In addition, the range of indications for PDT was determined exemplarily for the Eye Center at Medical Center, University of Freiburg and the Eye Center at St. Franziskus Hospital in Münster between 2006 and 2021. Finally, the estimated prevalence of CSC and an estimate of cases requiring treatment were used to calculate the number of patients in need of PDT treatment in Germany. RESULTS: The number of PDTs performed in Germany decreased from 1072 in 2006 to 202 in 2019. While PDT was used in 86% of cases in patients with nAMD and in 7% of cases with mCNV in 2006, it was mainly performed in patients with CSC (70%) and choroidal hemangiomas (21%) from 2016 to 2021. With an estimated incidence of CSC of 1:10,000 and assuming that 16% of patients develop chronic CCS requiring treatment, approximately 1330 PDTs would need to be performed per year in Germany for patients with newly diagnosed chronic CSC alone. CONCLUSION: The decreasing numbers of PDT treatment performed in Germany is mainly due to a change to intravitreal injections as the preferred treatment for nAMD and mCNV. As PDT is currently the recommended treatment of choice for chronic CSC, an underprovision of PDT in Germany can be assumed. To enable an appropriate treatment for patients, a reliable verteporfin production, a simplified approval process by health insurance companies and a close cooperation between ophthalmologists in private practice and larger centers are urgently needed.