Morphological and molecular changes in the Harderian gland of streptozotocin-induced diabetic rats.

Using a rat model of type 1 diabetes (T1D) obtained by treatment with streptozotocin, an antibiotic that destroys pancreatic ß-cells, we evaluated the influence of subsequent hyperglycemia on the morphology and physiology of the Harderian gland (HG). HG is located in the medial corner of the orbit of many terrestrial vertebrates and, in rodents, is characterized by the presence of porphyrins, which being involved in the phototransduction, through photo-oxidation, produce reactive oxygen species activating the autophagy pathway. The study focused on the expression of some morphological markers involved in cell junction formation (occludin, connexin-43, and α-tubulin) and mast cell number (MCN), as well as autophagic and apoptotic pathways. The expression of enzymes involved in steroidogenesis [steroidogenic acute regulatory protein (StAR), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD)] and the level of lipid peroxidation by thiobarbituric acid reactive species assay were also evaluated. The results strongly indicate, for the first time, that T1D has a negative impact on the pathophysiology of rat HG, as evidenced by increased oxidative stress, morphological and biochemical alterations, hyperproduction and secretion of porphyrins, increased MCN, reduced protein levels of StAR and 3ß-HSD, and, finally, induced autophagy and apoptosis. All the combined data support the use of the rat HG as a suitable experimental model to elucidate the molecular damage/survival pathways elicited by stress conditions.

Photosensitizers incorporation in SOPC films at different hydration levels.

In the present work, two photosensitizing drugs, Temoporfin and Verteporfin have been studied. Both have regular approval in Europe, Temoporfin for the treatment of head and neck cancers and Verteporfin for the treatment of age-related macular degeneration (AMD). The treatment modality, known as "Photodynamic Therapy" (PDT), involves drug activation with visible light in the presence of oxygen and production of reactive oxygen species (ROS) to destroy the pathological tissues. Both drugs are inactive in the absence of light, presenting only few side effects. The incorporation of the two drugs into a SOPC bilayer -used as a model membrane- was studied by ATR-FTIR. An original approach was applied, involving lyotropic transitions and a very slow dehydration rate of the sample. In low water content and dry film, Temoporfin highly affects stretching vibrations of SOPC chains and polar groups, showing that Temoporfin is inserted into the bilayer in both apolar and polar regions. In fully hydrated layers, Temoporfin - SOPC interactions still take place but only impact Temoporfin vibration bands. Verteporfin shows smaller effect on both chain and polar groups' vibrations of SOPC, with the exception of choline group, suggesting that Verteporfin is inserted into the bilayer to a lesser extent and remains at the bilayer polar interface. These results can be used to better understand drugs behavior in biological media.

Therapeutic effect of modified double-dose photodynamic therapy in circumscribed choroidal haemangioma.

AIMS: To retrospectively compare the therapeutic effect of modified double-dose photodynamic therapy (PDT) with standard-dose PDT in patients with circumscribed choroidal haemangioma (CCH). METHODS: Thirty-nine patients with CCH were categorised in two groups by PDT type. The standard-dose group (n=12) was treated with 6 mg/m2 verteporfin and a 689 nm laser for 83 s. The modified double-dose group (n=27) received one vial of verteporfin (15 mg), and the dose was calculated for each patient based on body surface area, then irradiance time was adjusted according to calculated verteporfin dose to achieve a 'double'-dose effect. Treatment outcomes (foveal centre thickness, subretinal fluid, tumour thickness and diameter) were measured at baseline and 1 year post-treatment; subretinal fluid levels were also measured at 1, 3 and 6 months post-treatment. RESULTS: No differences in baseline characteristics were found between the two groups. The modified double-dose group showed a greater reduction in tumour thickness (45.3% vs 20.6%, p=0.013) and tumour volume (60.0% vs 30.0%, p=0.006) at 1 year post-treatment. Recurred or non-complete resolution patients in the standard-dose group tended to show much increased subretinal fluid than those in the modified double-dose group at 1-year post-treatment. CONCLUSION: Modified double-dose PDT is an effective and safe protocol for symptomatic CCH management, greater tumour regression and potentially better resolution of subretinal fluid compared with standard PDT.

Comparison of the efficacy and safety between subthreshold micropulse laser, standard-fluence and low-fluence photodynamic therapy for chronic central serous chorioretinopathy.

PURPOSE: To compare the efficacy and safety of subthreshold micropulse laser treatment (SML), standard-fluence photodynamic therapy (PDT) and low-fluence PDT in patients with chronic central serous chorioretinopathy (cCSC). METHODS: This retrospective study included 52 eyes of 46 patients with chronic CSC who were treated with 577nm SML (n=23), standard-fluence PDT (verteporfin 6mg/m2 and light energy 50J/cm2) (n=13), or low-fluence PDT (verteporfin 6mg/m2 and light energy 25J/cm2) (n=16). The mean changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including central retinal thickness (CRT), subretinal fluid (SRF) height, and ellipsoid zone (EZ) disruption, over the follow-up period were evaluated. RESULTS: The mean follow-up period was 8.42±3.34 months. In the SML group, the SRF resolution time was longer than the other groups. At 1 month, the SML group's mean CRT was higher than the other groups. The BCVA improvement was statistically significant in all groups (P<0.05), but in the SML group, it was slower than the other groups. Three eyes in the low-fluence and one eye in the standard-fluence PDT group received a second PDT treatment. The mean number of SML treatments was 2.48±1.08. If the EZ was intact, the rate of complete resolution of SRF was higher than if the EZ was disrupted or lost. CONCLUSION: SML, standard-fluence PDT, and low-fluence PDT can all improve visual acuity in cCSC. Standard-fluence and low-fluence PDT induced a more rapid reabsorption of the fluid, improvement of BCVA, and equal safety compared with SML. More treatment sessions of SML were required than with the other treatment modalities.

Application of Porphyrins in Antibacterial Photodynamic Therapy.

Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current 'greener' methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.

Development of redox-responsive theranostic nanoparticles for near-infrared fluorescence imaging-guided photodynamic/chemotherapy of tumor.

The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs). The enhanced near-infrared (NIR) fluorescence intensity and reactive oxygen species (ROS) generation of Ce6 were observed in a reductive environment, suggesting the cystamine-switched "ON/OFF" of Ce6. Also, the in vitro release of PTX exhibited a redox-triggered profile. MCF-7 cells showed a dramatically higher uptake of Ce6 delivered by CHT NPs compared with free Ce6. The improved therapeutic effect of PTX/CHT NPs compared with mono-photodynamic or mono-chemotherapy was observed in vitro via MTT and apoptosis assays. Also, the PTX/CHT NPs exhibited a significantly better in anti-tumor efficiency upon NIR irradiation according to the results of in vivo combination therapy conducted on 4T1-tumor-bearing mice. The in vivo NIR fluorescence capacity of CHT NPs was also evaluated in tumor-bearing nude mice, implying that the CHT NPs could enhance the accumulation and retention of Ce6 in tumor foci compared with free Ce6. Interestingly, the anti-metastasis activity of CHT NPs was observed against MCF-7 cells by a wound healing assay, which was comparable to LMWH, suggesting LMWH was promising for construction of nanocarriers for cancer management.

SHORT-TERM FINDINGS ON OPTICAL COHERENCE TOMOGRAPHY AND MICROPERIMETRY IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY PATIENTS TREATED WITH HALF-DOSE PHOTODYNAMIC THERAPY.

PURPOSE: To assess the short-term outcome of and possible temporary vision loss after half-dose verteporfin photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (cCSC). METHODS: In this prospective study, 14 eyes of 13 cCSC patients who underwent half-dose PDT were included. Patients received spectral-domain optical coherence tomography (OCT) imaging and microperimetry before PDT on the day of treatment and 1 week after treatment. RESULTS: Five patients (38%) reported worsening of visual complaints in the week after half-dose PDT. No significant changes in both central foveal thickness, height of subretinal fluid, and choroidal thickness on optical coherence tomography imaging and retinal sensitivity on microperimetry were observed, neither in the patients who did not experience worsening of visual symptoms, nor in those who did. CONCLUSION: Worsening of visual complaints can occur in a noteworthy number of cCSC patients in the first week after half-dose verteporfin PDT. Despite the fact that no significant short-term changes on both optical coherence tomography and microperimetry have been detected in this study, the assessment could be of importance for the long-term outcome of treatment and needs further investigation.

The effect of photodynamic therapy with talaporfin sodium, a second-generation photosensitizer, on oral squamous cell carcinoma: A series of eight cases.

OBJECTIVE: To assess the effect of photodynamic therapy (PDT) with talaporfin sodium, a second-generation photosensitizer, on oral squamous cell carcinoma (SCC). METHODS: Eight patients who were diagnosed with oral SCC without any metastasis and underwent talaporfin sodium-mediated PDT (t-PDT) were included in this study. Biopsies were performed 4-6 weeks after t-PDT. The clinical response was evaluated using Response Evaluation Criteria in Solid Tumors. RESULTS: Complete response (CR) was achieved in six of eight cases, and two cases showed partial response (PR) as a clinical outcome of t-PDT. Recurrence occurred in one of the CR cases 9 months after irradiation. The patient underwent tumor resection and no recurrence was found after surgery. The two cases with PR died from the cancer despite additional PDT. CONCLUSION: t-PDT is an effective treatment strategy for oral SCC. Talaporfin sodium has an advantage with regard to early elimination from the body compared with porfimer sodium.

Establishment and characterization of human osteosarcoma cells resistant to pyropheophorbide-α methyl ester-mediated photodynamic therapy.

The present study was performed to establish and characterize new human osteosarcoma cell lines resistant to pyropheophorbide-α methyl ester­mediated photodynamic therapy (MPPa-PDT). MPPa-PDT-resistant cells are isolated from the human osteosarcoma MG63 and HOS cell lines and two resistant populations were finally acquired, including MG63/PDT and HOS/PDT. Cell Counting Kit-8 (CCK-8) assay was used to determine the MPPa-PDT, cisplatin (CDDP) resistance and proliferation of MG63, MG63/PDT, HOS and HOS/PDT cells. The intracellular ROS were analyzed using DCFH-DA staining. The colony formation, invasion and migration of parental and resistant cells were compared. FCM was employed to examine the cell cycle distribution, the apoptosis rate and the proportion of CD133+ cells. The fluorescence intensity of intracellular MPPa was observed by fluorescence microscopy and quantified using microplate reader. The protein levels were assessed by western blotting (WB). Compared with two parental cells, MG63/PDT and HOS/PDT were 1.67- and 1.61-fold resistant to MPPa-PDT, respectively, and also exhibited the resistance to CDDP. FCM assays confirmed that both MG63/PDT and HOS/PDT cells treated with MPPa-PDT displayed a significantly lower apoptosis rate in comparison with their corresponding parental cells. The expression of apoptosis-related proteins (i.e. cleaved-caspase 3 and cleaved­PARP), intracellular ROS and the antioxidant proteins (HO-1 and SOD1) in MG63/PDT and HOS/PDT cells was also lower than that in parental cells. Both MG63/PDT and HOS/PDT cells exhibited changes in proliferation, photosensitizer absorption, colony formation, invasion, migration and the cell cycle distribution as compared to MG63 and HOS cells, respectively. Compared to MG63 and HOS cells, both resistant cell lines had a higher expression of CD133, survivin, Bcl-xL, Bcl-2, MRP1, MDR1 and ABCG2, but a lower expression of Bax. The present study successfully established two resistant human osteosarcoma cell lines which are valuable to explore the resistance-related mechanisms and the approaches to overcome resistance.

Incidence, outcomes, and risk factors for hemorrhagic complications in eyes with polypoidal choroidal vasculopathy following photodynamic therapy in Indian subjects.

PURPOSE: To evaluate the incidence, outcomes, and risk factors for hemorrhagic complications in eyes with polypoidal choroidal vasculopathy (PCV) following photodynamic therapy (PDT). METHODS: Medical records of 94 eyes of 86 consecutive patients with PCV who underwent PDT between January 2007 and December 2014 were retrospectively reviewed. The diagnosis of PCV was based on clinical features and indocyanine green angiography. Eyes were treated with PDT monotherapy or a combination of PDT plus anti-vascular endothelial growth factor. PDT was performed at (standard [SFPDT] or reduced fluence RFPDT). RESULTS: Ninety-four eyes had 119 PDT treatment sessions (mean: 1.3 sessions). Mean presenting vision was 0.46 ± 0.44 logarithm of the minimum angle of resolution (logMAR). Following PDT, ten eyes (11%) of nine patients had hemorrhagic complications such as subretinal hemorrhage (SRH; n = 5), subretinal pigment epithelium (RPE) hemorrhage (n = 1), breakthrough vitreous hemorrhage (BVH; n = 3), and SRH with sub-RPE hemorrhage and BVH (n = 1). Median interval to hemorrhage following PDT was 2 months. Age (P = 0.842), duration of symptoms (P = 0.352), number of laser spots (P = 0.219), and laser spot size (LSS) (P = 0.096) were not significantly associated with increased risk of hemorrhagic complications. Female gender was associated with reduced risk of hemorrhage (P = 0.045). SFPDT was significantly associated with increased risk of hemorrhage (P = 0.026). The probability of developing hemorrhagic complications in SFPDT group was 0.24 compared to 0.07 in RFPDT group (P = 0.039). Multivariate logistic regression analysis showed SFPDT as the only significant risk factor for hemorrhage following PDT (odds ratio 5.3, 95% confidence interval 1.1-24.8, P = 0.03). Mean final vision was 0.61 ± 0.53 logMAR at mean follow-up of 33 months (median = 22 months; range = 2-157 months). CONCLUSION: Age, LSS, number of laser spots, preexisting hemorrhages, or use of anticoagulants were not associated with increased risk of hemorrhagic complications. SFPDT was significantly associated with increased risk of hemorrhagic complications in such eyes.

Choroidal neovascular membrane in a treated choroidal hemangioma.

Association of choroidal neovascular (CNV) membrane with circumscribed choroidal hemangioma is rare, and the CNV development after photodynamic therapy (PDT) is also rare. Etiopathogenesis of these associations is poorly understood. We noted the development of CNV over choroidal hemangioma after PDT therapy in a young female patient in our hospital. Temporal association of CNV development after PDT treatment points toward the possible side effects of PDT. Repeat injections of antivascular endothelial growth factor (ranibizumab) regressed the CNV resulting in a favorable visual outcome.

Safety evaluation of repeated intravenous infusion of sinoporphyrin with and without PDT in rats.

Photodynamic therapy (PDT) is a promising antineoplastic modality in the oncology field. We assessed the safety of repeated intravenous administrations of sinoporphyrin, a porphyrin derivative, with and without illumination in rats. Toxicokinetic studies of single and multiple administrations of sinoporphyrin were also carried out. Sprague-Dawley rats were randomly assigned to the dark-toxicity and PDT groups. Animals in the dark toxicity group received an i.v. infusion of sinoporphyrin at 3 doses: 2 mg kg-1, 6 mg kg-1, and 18 mg kg-1. The PDT group included 2 doses of sinoporphyrin (2 mg kg-1 and 18 mg kg-1), and the rats received 60 J of 630 nm laser illumination 24 h after photosensitizer infusion. The treatments were repeated every 7 days for 5 cycles and were followed by a 14-day recovery period. Systematic analyses were conducted at the end of treatment and recovery periods. Blood samples were obtained 5 min, 30 min, 2 h, 8 h, 24 h, 48 h, 72 h, and 96 h after the first and fifth treatments for toxicokinetic studies. Sinoporphyrin-PDT led to the death of one out of 270 rats; the dead animal had been treated with 18 mg kg-1 sinoporphyrin and died at the end of the fifth PDT treatment. Liver injury, the primary toxicity observed in the study, was identified using biochemical tests, necropsy, and histopathology. Elevated white blood cell and neutrophil counts were found in the rats in both the dark toxicity and PDT groups. Skin lesions at the illumination site were obvious in the PDT group. Pigment deposits were detected in multiple organs such as the liver, spleen, lymph nodes, and ovaries in the 6 mg kg-1 and 18 mg kg-1 groups. No other abnormalities were observed. The toxicokinetic parameters of single and multiple sinoporphyrin administrations were calculated and compared. Repeated sinoporphyrin administrations both alone and in combination with laser illumination were tolerable, and all toxicities were transient. The no observed adverse effect level (NOAEL) for repeated sinoporphyrin administration and sinoporphyrin-PDT was 6 mg kg-1 and 2 mg kg-1, respectively. Further studies are warranted.

Intestinal Epithelial Cell-Intrinsic Deletion of Setd7 Identifies Role for Developmental Pathways in Immunity to Helminth Infection.

The intestine is a common site for a variety of pathogenic infections. Helminth infections continue to be major causes of disease worldwide, and are a significant burden on health care systems. Lysine methyltransferases are part of a family of novel attractive targets for drug discovery. SETD7 is a member of the Suppressor of variegation 3-9-Enhancer of zeste-Trithorax (SET) domain-containing family of lysine methyltransferases, and has been shown to methylate and alter the function of a wide variety of proteins in vitro. A few of these putative methylation targets have been shown to be important in resistance against pathogens. We therefore sought to study the role of SETD7 during parasitic infections. We find that Setd7-/- mice display increased resistance to infection with the helminth Trichuris muris but not Heligmosomoides polygyrus bakeri. Resistance to T. muris relies on an appropriate type 2 immune response that in turn prompts intestinal epithelial cells (IECs) to alter differentiation and proliferation kinetics. Here we show that SETD7 does not affect immune cell responses during infection. Instead, we found that IEC-specific deletion of Setd7 renders mice resistant to T. muris by controlling IEC turnover, an important aspect of anti-helminth immune responses. We further show that SETD7 controls IEC turnover by modulating developmental signaling pathways such as Hippo/YAP and Wnt/ß-Catenin. We show that the Hippo pathway specifically is relevant during T. muris infection as verteporfin (a YAP inhibitor) treated mice became susceptible to T. muris. We conclude that SETD7 plays an important role in IEC biology during infection.

Half-dose Versus Half-time Photodynamic Therapy for Central Serous Chorioretinopathy.

PURPOSE: To compare the efficacy of half-dose vs half-time photodynamic therapy (PDT) guided by fluorescein angiography (FA) for the treatment of central serous chorioretinopathy (CSC). DESIGN: Two-center, retrospective, comparative case series. METHODS: Sixty-one eyes with acute or chronic CSC involving fovea were recruited; 35 eyes received half-dose PDT and 26 eyes received half-time PDT. Improvement in best-corrected visual acuity (BCVA), resolution of subretinal fluid (SRF) demonstrated by optical coherence tomography (OCT), and recurrence of CSC after PDT were compared between the 2 groups. RESULTS: The mean follow-up time after PDT was 14.8 ± 13.3 months. Both groups showed significant improvement in BCVA at months 1, 3, 6, and 12 after PDT (P < .05 for all times). Multiple regression analysis showed that PDT type was not correlated with visual improvement (P > .05 for all times). All eyes that received half-time PDT showed complete resolution of SRF within 6 months after PDT, but 3 eyes that received half-dose PDT had persistent SRF before loss to follow-up at months 5, 7, and 8 (P = .21 between 2 groups). Three of 32 eyes in the half-dose group and 2 of 26 eyes in the half-time group had recurrence of CSC during follow-up; all recurrent cases had complete SRF resolution after another PDT treatment. No adverse systemic or ocular side effects were observed in any cases. CONCLUSIONS: Half-dose and half-time FA-guided PDT were both effective and safe in treating CSC and showed similar efficacy in visual improvement and SRF resolution.

[Half-Dose Verteporfin Photodynamic Therapy (hdPDT) in the Treatment of Central Serous Chorioretinopathy]. / Photodynamische Therapie mit halber Verteporfin-Dosis zur Behandlung der Chorioretinopathia Centralis Serosa.

BACKGROUND: To estimate the efficacy and safety profile of half-dose photodynamic therapy (hdPDT) for treating central serous chorioretinopathy (CSC). PATIENTS AND METHODS: An interventional, retrospective case series of patients with CSC (symptoms ≧ 3 months) receiving half-dose PDT (3 mg/m2 verteporfin). The ophthalmic examination at baseline and at 8 and 16 weeks after treatment included slit-lamp biomicroscopy, indirect ophthalmoscopy, measurement of intraocular pressure (IOP), ETDRS best-corrected visual acuity (BCVA), Amsler grid screening and contrast visual acuity (CVA). Fluorescein angiography (FA), autofluorescence (FAF) and optical coherence tomography (OCT) were measured at each visit. Central macular thickness (CMT) was measured automatically. RESULTS: 12 eyes of 12 patients (10 male and 2 female patients; mean age 46.6 ± 7.91 years) were included in this study. Anatomical resolution was obtained in 10 eyes (83.4 %) at week 16, but 2 eyes (16.6 %) exhibited persistent SRD throughout the follow-up period. Baseline CMT decreased from initially 330.1 µm ± 131.3 to 205.6 µm ± 97.6 (p = 0.034) at week 8 and to 220.3 µm ± 120.1 (p = 0.05) at week 16. Visual acuity (number of total letters read) significantly improved from initially 82.8 ± 11.5 to 86.8 ± 13.9 at week 8 and 91.3 ± 13.8 at week 16 (p = 0.012). Contrast visual acuity (calculated decimal visual acuity) significantly improved from initially 0.14 ± 0.09 to 0.38 ± 0.28 (p = 0.002) at week 16. After therapy, no significant changes in RPE could be detected with FAF and no ocular adverse events were observed. CONCLUSION: PDT with half-dose verteporfin resulted in reduced leakage in FA, enhanced visual acuity and resolution of subretinal fluid in OCT in patients with CSC, with no detected side effects of treatment.

Analysis of the in vivo and in vitro effects of photodynamic therapy on breast cancer by using a sensitizer, sinoporphyrin sodium.

Photodynamic therapy (PDT) is an emerging theranostic modality for various cancers and diseases. Photosensitizers are critical components for PDT. Sinoporphyrin sodium, referred to as DVDMS, is a newly identified photosensitizer that was isolated from Photofrin. Here, we evaluated the effects of DVDMS-mediated PDT (DVDMS-PDT) on tumor cell proliferation and metastasis in the highly metastatic 4T1 cell line and a mouse xenograft model. DVDMS-PDT elicited a potent phototoxic effect in vitro, which was abolished using the reactive oxygen species (ROS) scavenger N-acetylcysteine. In addition, DVDMS-PDT effectively inhibited the migration of 4T1 cells in scratch wound-healing and transwell assays. Using an in vivo mouse model, DVDMS-PDT greatly prolonged the survival time of tumor-bearing mice and inhibited tumor growth and lung metastasis, consistent with in vitro findings. PDT with DVDMS had a greater anti-tumor efficacy than clinically used Photofrin. Moreover, preliminary toxicological results indicate that DVDMS is relatively safe. These results suggest that DVDMS is a promising sensitizer that warrants further development for use in cancer treatment with PDT or other sensitizing agent-based therapies.

Vascular-targeted photodynamic therapy in the treatment of neovascular age-related macular degeneration: Clinical perspectives.

Vascular targeted photodynamic therapy (VTP), with use of verteporfin as a photosensitizer is one of the few therapies, which has been shown to effectively slow the progression of the "wet" form of age-related macular degeneration (AMD), and even to stabilize visual acuity over many years. Although, due to considerable advance of AMD treatment, it is currently not recommended in monotherapy of AMD, however, its combination with steroids and anti-angiogenic biologic drugs may reveal high therapeutic potential in the treatment of neovascular AMD. The future of VTP as a method of AMD treatment is development of new selective and targeted photosensitizer and combination of this method with other therapeutic strategies targeting cellular structures or pathways involved in AMD progression.

A 50% vs 30% dose of verteporfin (photodynamic therapy) for acute central serous chorioretinopathy: one-year results of a randomized clinical trial.

IMPORTANCE: A randomized clinical trial is needed to evaluate what is the best photodynamic therapy (PDT) protocol to use for acute central serous chorioretinopathy. OBJECTIVE: To compare the efficacy and safety of a 50% dose of verteporfin (a method of PDT) with the efficacy and safety of a 30% dose for acute central serous chorioretinopathy. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, noninferiority, double-masked, randomized, controlled, clinical trial in which 131 patients (131 eyes) with acute central serous chorioretinopathy for less than 6 months were recruited with a follow-up of 12 months from university-based ophthalmology practices. INTERVENTIONS: Patients were randomly assigned to either a 50% dose of verteporfin (the 50%-dose PDT group) or a 30% dose (the 30%-dose PDT group). MAIN OUTCOMES AND MEASURES: The 2 primary outcome measures were the proportion of eyes with complete absorption of subretinal fluid and the proportion of eyes with complete disappearance of fluorescein leakage at 6 and 12 months. The secondary outcome measures included the subretinal fluid recurrent rate, the fluorescein leakage recurrent rate at 12 months, the mean best-corrected visual acuity, the retinal thickness of the foveal center, and the maximum retinal thickness at each scheduled visit. RESULTS: The noninferiority of the 30%-dose PDT compared with the 50%-dose PDT for the primary outcomes was not demonstrated. The optical coherence tomography-based improvement rate in the 30%-dose PDT group was less than that in the 50%-dose PDT group both at 6 months (73.8% vs 92.9%; α = 0.0125, P = .006) and at 12 months (75.4% vs 94.6%; α = 0.0125, P = .004). The fluorescein angiography-based improvement rate in the 30%-dose PDT group was less than that in the 50%-dose PDT group both at 6 months (68.9% vs 91.1%; α = 0.0125, P = .003) and at 12 months (68.9% vs 92.9%; α = 0.0125, P = .001). The subretinal fluid recurrence rate in the 30%-dose PDT group was greater than that in the 50%-dose PDT group (24.0% vs 5.7% at 12 months; P = .010, determined by use of the log-rank test). The fluorescein leakage recurrent rate in the 30%-dose PDT group was significantly higher than that in the 50%-dose PDT group (16.7% vs 3.8% at 12 months; P = .03, determined by use of the log-rank test). No ocular adverse event was encountered in the study. CONCLUSIONS AND RELEVANCE: A 50% dose of verteporfin may be more effective at resolving subretinal fluid and fluorescein leakage, and with better visual outcomes, than a 30% dose for acute central serous chorioretinopathy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01574430.

The chorioretinal damage caused by different half parameters of photodynamic therapy in rabbits.

PURPOSE: To compare the chorioretinal tissue response after different half-strength parameters of photodynamic therapy (PDT) in rabbits. METHODS: The study included 4 groups, and each group contained 4 animals. The full dose served as the control group: verteporfin (4 mg/kg) with 600 mW/cm(2) irradiance from a diode laser at 689 nm applied to the retina for 8 s. One parameter was changed to half-strength in the other 3 groups. The HLaser group received half-strength laser irradiance. The HTime group was exposed to photosensitization for half the time, and the HDose group received half the drug dose. Six laser spots were generated in each of the eyes of every rabbit and documented graphically. The lesions were examined on days 1, 7, and 42 after PDT treatment using color fundus imaging, fluorescein angiography (FA), and histopathology analysis. RESULTS: PDT treatment in rabbits caused chorioretinal damage in all 4 groups. FA on day 1 showed that the use of half the laser irradiance, half the drug dose, or half the photosensitizing time tended to decrease the damage to the chorioretinal tissue in terms of the number of occlusions and the area of occlusion, but only the results from half the laser irradiance were significantly different. In addition, the HLaser and HDose groups showed significantly less apoptosis by TUNEL staining on day 1. CONCLUSIONS: Among these PDT parameters, decreasing the laser irradiance by half showed the greatest decrease in chorioretinal damage in an experimental animal model.

Massive exudative retinal detachment following photodynamic therapy for retinal hemangioma in von Hippel-Lindau Syndrome.

Photodynamic therapy (PDT) is a common treatment on retinal capillary hemangioma. We applied PDT to a patient with von Hippel-Lindau(VHL) syndrome and she developed severe massive exudative retinal detachment the next day, which is a rare complication for PDT. After intraocular anti-VEGF agent and peribulbar dexamethasone several times to the patient, her subretinal fluid disappeared and hemangiomas atrophied. Treatment with Anti-VEGF agent and corticosteroid is effective for such complication.