Design, synthesis and antitumor activities of chlorin p6 ether derivatives as photosensitizer for photodynamic therapy / 药学实践杂志

Objective To designe, synthesize a series of chlorin p6 ether photosensitizers and preliminarily investigate their photodynamic antitumor activity based on previous research results that alkoxyl ether derivatives of 3-vinyl on chlorin f exhibited stronger photosensitive antitumor activity than parent compound. Methods Purpurin-18 (4) was obtained by oxidative degradation with air and alkali on pheophorbide a (5) which was prepared through acid hydrolysis of chlorophyll a from crude chlorophyll extracts in Chinese traditional herb named Silkworm excrement. Then, chlorin p6 trimethylester (2) were formed via basic hydrolysis of internal anhydride ring for lead compound 3 and following immediately methylation with CH2N2. The intermediate 2 reacted with 33% HBr, following nucleophilic substitution with various alkoxyl alcohol to get six title compounds (1). All title compounds were subjected to photodynamic antitumor activity screening for melanoma B16-F10 cell in vitro. Results All title compounds showed much higher phototoxicity against melanoma B16-F10 cells than talaporfin and verteporfin. Their structures were confirmed by 1H-NMR, 13C-NMR, ESI-MS and ESI-HRMS spectra. Conclusion Chlorin p6 ether compounds were promising candidate photosensitizers for PDT applications due to theirs high dark toxicity/phototoxicity ratio and excellent phototoxicity, which were worthy of further research and development.

Photodynamic Therapy of Choroidal Neovascularization in Age-Related Macular Degeneration with Verteporfin: An Analysis of 10 Years of Clinical Results

PURPOSE: To analyze the long-term results of photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD). METHODS: The clinical data of patients treated with photodynamic therapy for exudative age-related macular degeneration between April 2000 and December 2000 were analyzed. Patients were followed-up for at least 10 years after PDT. RESULTS: Twenty-nine eyes of 29 patients were enrolled. Mean visual acuity on the logarithm of the minimum angle of resolution (log MAR) scale was 0.78 +/- 0.34 at baseline, 1.01 +/- 0.42 at 60 months, and 1.02 +/- 0.41 at 120 months. Predominantly classic, minimally classic, and occult without classic choroidal neovascularization was noted in 51.7%, 17.2%, and 31.1% of patients, respectively. Visual acuity was improved by 1 or more lines in 27.6% of patients and was unchanged in 20.7% of patients, while 51.7% of patients had lost 1 or more lines of visual acuity by 120 months. Baseline visual acuity and age were associated with the final visual prognosis (p < 0.05). Four patients developed neovascular AMD in the contralateral eye. CONCLUSIONS: PDT is safe and effective for neovascular AMD. However, AMD can recur at any time and thus patients should be followed-up for a long period of time.

Topical ALA-Photodynamic Therapy for Acne Can Induce Apoptosis of Sebocytes and Down-regulate Their TLR-2 and TLR-4 Expression

BACKGROUND: Although photodynamic therapy (PDT) is widely performed for acne, little is known about its exact therapeutic mechanism. OBJECTIVE: We aimed to estimate the efficacy and safety of PDT on acne and to discover its mode of action. METHODS: We performed PDT on 12 patients with mild to moderate acne. The clinical efficacy was assessed by counting the acne lesions and measuring the sebum secretion before and after PDT. In addition, we took biopsy samples from the peri-lesional areas before and after 3-session of PDT. To examine the degree of apoptosis of the sebaceous follicles, TUNEL assay was performed. To investigate the changes of toll-like receptor (TLR)-2 and TLR-4 expression after PDT, immunohistochemical stainings were also carried out. Finally, we performed TUNEL assay using the cultured sebocytes to confirm the apoptosis of sebocytes in vitro after PDT. RESULTS: There was a significant reduction in the number of inflammatory acne lesions after PDT, compared to baseline (p<0.05). Sebum excretion significantly decreased 2 weeks after the first PDT session except for one patient (p<0.05). The TUNEL positive cells in the peri-lesional sebaceous glands after PDT markedly increased, compared with those of before PDT. A decrease in TLR-2 and TLR-4 expression by sebaceous glands and epidermis after PDT was 50% and 30%, respectively. CONCLUSION: Our results demonstrate that apoptosis of the sebaceous glands is associated with improvement of acne by PDT. PDT has shown to down-regulate TLR-2 and TLR-4 expression in the sebaceous glands and epidermis of acne patients.

Photodynamic Therapy Combined with CO2 Laser Vaporization on Disseminated Superficial Actinic Porokeratosis: A Report of 2 Cases on the Face

Disseminated superficial actinic porokeratosis (DSAP) is a skin condition that usually shows a poor response to different modalities of treatment. Herein we describe 2 patients with DSAP on the face, each treated with 3 to 4 sessions of photodynamic therapy combined with laser vaporization.

In vivo study of photodynamic therapy using a new photosensitizer, 9-hydroxypheophorbide-a and 670 nm diode laser on HT-3 cervical cancer cell / 대한산부인과학회지

OBJECTIVE: During the last several years, such as Photofrin(R), Photogem(R), HpD, and 5-aminolevulenic acid (ALA) has been used as photosensitizers for a wide range of malignant tumors as well as non-malignant disease. A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a) was derived from Spirulina platensis. The aim of this study was to evaluate the anticancer effect and mechanism of photodynamic therapy in vivo using 9-HpbD-a and 670 nm diode laser on a HT-3 cervical cancer cell line. METHODS: PDT effects were observed in xenograft nude mouse model. HT-3 cell line was xenografted into the subcutaneous space of the mouse back. When the tumors grew up to 400~500 mm3, the animals were randomly separated into 4 groups: Group I (n=5), control group; group II (n=10), 9-HpbD-a alone; group III (n=10), laser irradiation alone; and group IV (n=20), PDT in nude mouse group. RESULTS: PDT treated group (9-HpbD-a+laser irradiation) showed complete response (15/20, 75%), recurrence (3/20, 15%) or no response (2/20, 10%). PDT group showed significant remission rate, comparing to laser irradiation alone group, 9-HpbD-a alone group and untreated control group (P<0.05). When PDT using 9-HpbD-a, tumor size was decrease and microscopically finding, antitumor effect was showed inflammation and necrosis of tumor cell. Overexpression of p53 and Ki-67 gene had been detected at the HT-3 cervical cancer cell and 10 days after PDT. And no experssion in normal tissue and tumor after PDT. So, immunohistochemical study of p53 and Ki-67 gene correlated with PDT for anticancer effect. CONCLUSION: These results suggest that 9-HpbD-a is one of the promising photosensitizers for the future and would be needed to use 9-HpbD-a as a photosensitizer in clinical setting. We would further suggest that photodynamic therapy is a more effective method than the conventional treatment for women who want to maintain their anatomical and functional uterine cervix.

The anticancer effect and mechanism of photodynamic therapy using a new photosensitizer and diode laser on cervical cancer cell / 대한산부인과학회지

OBJECTIVE: During the last several years, such as Photofrin(R), Photogem(R), HpD, and 5-aminolevulenic acid (ALA) has been used as photosensitizers for a wide range of malignant tumors as well as non-malignant disease. A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a) was derived from Spirulina platensis. The aim of this study was to evaluate the anticancer effect and mechanism of photodynamic therapy in vitro using 9-HpbD-a and 670 nm diode laser on a HT-3 cervical cancer cell line. METHODS: We studied the cytotoxic effect of 9-HpbD-a and 670 nm diode laser in HT-3 cervical cancer cell line. The cultured HT-3 cells were treated with serial concentrations of 9-HpbD-a followed by various irradiation time (0, 5, 15, 30 min) and by various interval times (0, 3, 6, 9, 12 24 hours) until laser irradiation, then 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl-tetrazolium bromide (MTT) assay was applied to measure the relative inhibitory effect of PDT. RESULTS: Optimal condition for laser irradiation time was 15 minutes and the cytotoxic effect according to the incubation time after 9-HpbD-a treatment was increased until 6 hours. Under confocal microscopy, to observe intracellular localization of 9-HpbD-a, cells dual-stained with 9-HpbD-a and panel of organelle-specific fluorescence probes (MitoTracker, LysoTracker, ER-Tracker), endoplasmic reticulum (ER) as a major accumulation organelle site in HT-3 cervical cell line for this new photosensitizer. CONCLUSION: The anticancer effect of PDT using 9-HpbD-a is effective in HT-3 cervical cancer cell line. This agent therefore represents a promising photosensitizing prodrug for the treatment of cervical cancer with PDT in clinical setting for the future.

Treatment of primary carcinomas of facial skin by photodynamic therapy with topical δ-aminolaevulinic acid / 中华医学美学美容杂志

Objective To evaluate the effects of δ-aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of primary carcinomas on the facial skin. Methods In the accordance of these tumors' sites and morphology, 14 patients with squamous cell carcinoma (SCC), 38 patients with basal cell carcinoma (BCC) and 5 patients with Bowen disease were given four to eight times of topical ALA followed by PDT. Results Ten (71.4%) SCC cases, 34 (89.5%) BCC cases and all (100%) Bowen disease cases completely recovered after ALA-PDT. The others all obtained signifi-cant improvement after final treatment. Their unaffected tissues around these tumors kept well and no scaring appeared after ALA-PDT. The recurrence rates among the completely-recovered cases were 10.0% (SCC), 11.8% (BCC) and 0% (Bowen disease), respectively, by the end of six-month's follow-up. Conclusions Topical ALA-PDT is an effective new therapeutical method with lower recur-rence rates, fewer side effects, no scar formation and excellent cosmetic results for primary carcinomas localizing on the facial skin.

The Effect of Photodynamic Therapy with Verteporfin Retreatment on Corneal Neovascularization in Rabbits

PURPOSE: This study evaluated the effect and safety of photodynamic therapy (PDT) with verteporfin retreatment on patients with corneal neovascularization. METHODS: Corneal neovascularization was induced with a silk suture of the corneal stroma in 24 white rabbits (48 eyes). Four rabbits were examined histologically before performing PDT. Ten rabbits were chosen randomly, one eye from each rabbit was treated with PDT at 50 J/cm2, and the other eye was used as a control. Both eyes of the remaining 10 rabbits were treated with PDT at 150 J/cm2. One week later, one eye was further retreated with PDT at the same intensity. The area of corneal neovascularization was measured and evaluated histologically using light and electron microscopies. RESULTS: The least neovascularized area was observed in the retreated group (P=0.04). The histologic examination revealed fewer new corneal vessels in the retreated group, but the corneal epithelium, stroma, and endothelium showed a normal appearance. Results from electron microscopic examination demonstrated thrombi as well as destruction and nuclear fragmentation of the vascular endothelial cells. However, there were no other changes in the cornea except for vascular endothelial cells, even in the retreated group. CONCLUSIONS: In conclusion, these results suggest that PDT with verteporfin retreatment appears to be safe and significantly more effective in patients with regression of corneal neovascularization.

Photodynamic Therapy for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

PURPOSE: To investigate the effects of repeated photodynamic therapy (PDT) for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) in Korean patients. METHODS: Clinical data of patients who were treated with repeated (3 times or more) PDT for subfoveal choroidal neovascularization secondary to AMD and followed up for more than 6 months were collected from 17 hospitals around the country. Visual outcomes at 12 and 24 months, follow-up were compared between subtypes of choroidal neovascularization. The factors related to final visual prognosis and PDT-related adverse effects were evaluated. RESULTS: 244 patients (244 eyes) were recruited (male: 60%, age: 67.7+/-9.1 years). The portion of patients with predominantly classic, minimally classic, and occult without classic choroidal neovascularization was 57%, 13%, and 24%, respectively and that of patients with visual improvements or less than moderate visual loss at 24 months follow-up were 28%, 38%, 30% and 47%, 56%, and 65%, respectively. Baseline visual acuity and age were significantly related to the final visual prognosis (p<0.05). PDT-related adverse events developed in 15 (6.1%) patients, but most were mild and transient. CONCLUSIONS: Repeated PDT for subfoveal choroidal neovascularization secondary to AMD has effects comparable to those of previous prospective, controlled trials without any significant safety concerns in Korea.

ROS Formation and the Mechanism of Photodynamic Therapy Using 9-Hydroxypheophorbide-a on AMC-HN3 Human Head and Neck Carcinoma Cell Line / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: During PDT, photosensitizer accumulates in the cell and irradiation forms ROS. ROS leads to activation of apoptoticpathway and cell death. Elevated intracellular calcium is known to play important role in apoptotic pathway. There are two type of ROS formation. The type of ROS formation differs in type of photosensitizers. We designed the experiment to define the relationship of ROS and cell death in PDT. MATERIALS AND METHOD: AMC-HN3 cells were cultured. Using a CaspACE assay kit, we measured caspases-3 activity after PDT. We also observed intra-cellular calcium concentrations using confocal microscopy (calcium green-1 stain) after PDT. To determine which type of reaction occursduring ROS formation, MTT assay was performed. RESULTS: Confocal microscopy showed that ROS had formed at the site of photosensitizer formation after PDT. After PDT, intracellular calcium increased. MTT assay showed more viability increase in blocking type II reaction. Caspase assay showed highest level after 4hrs. CONCLUSION: ROS is formed at the site photosentizer formation after PDT. Type II reaction was the main type of ROS formation. Apoptosis was main pathway of cell death in low dose of photosensitizer after PDT.

Photodynamic Therapy Results of Retinal Angiomatous Proliferation with Pigmented Epithelial Detachment in Age-related Macular Degeneration

PURPOSE: To evaluate the incidence of retinal angiomatous proliferation (RAP) and retinal pigmented epithelial detachment (PED) in Korean age-related macular degeneration (ARMD) patients and results of photodynamic therapy (PDT) with verteporfin. METHODS: Between May 2001 and December 2004, two hundred fifty-eight patients diagnosed of ARMD were evaluated and nine eyes of seven patients were as having RAP with PED. All patients underwent two or more sessions of PDT. Best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography and ICG angiography were performed before and after treatment. RESULTS: The incidence of RAP with PED was 2.8%. The mean age of onset was 71.7 and five of seven patients were female. After 17 months and mean 2.3 PDT treatments, mean BCVA decreased from 0.2 to 0.04. In two eyes, additional Transpupillary thermotherapy was undertaken. Occlusion of RAP and flattening of PED was observed in one eye, and four evolved toward stage 3 RAP. Three eyes with PDT developed tear of retinal pigmented epithelium. CONCLUSIONS: Korean ARMD patients showed a low incidence of RAP and poor visual outcomes even with treatment.

OPTIMIZATIONS FOR 5-AMINOLEVULINIC ACID BASED PHOTODYNAMIC THERAPY IN PURGING LEUKEMIA CELL HL60 / 药物分析学报

Objective To optimize experimental parameters for the photosensitization of 5-aminolevulinic acid (ALA) in promyelocytic leukemia cell HL60 and compare them with normal human peripheral blood mononuclear cell (PBMC). Methods ALA incubation time, wavelength applied to irradiate, concentration of ALA incubated, irradiation fluence may modulate the effect of 5-aminolevulinic acid based Photodynamic Therapy (ALA-PDT).The high-pressure mercury lamps of 400W served as light source, the interference filter of 410nm, 432nm, 545nm, 577nm were used to select the specific wavelength. Fluorescence microscope was used to detect the fluorescence intensity and location of protoporphyrin IX (PpIX) endogenously produced by ALA. MTT assay was used to measure the survival of cell. Flow cytometry with ANNEXIN V FITC kit (contains annexin V FITC, binding buffer and PI) was used to detect the mode of cell death. Results ① 1mmol/L ALA incubated 1×105/mL HL60 cell line for 4 hours, the maximum fluorescence of ALA induced PpIX was detected in cytomembrane. ② Irradiated with 410nm for 14.4J/cm2 can result in the minimum survivability of HL60 cell. ③ The main mode of HL60 cell death caused by ALA-PDT is necrosis. Conclusion ALA for 1mmol/L, 4 hours for dark incubation time, 410nm for irradiation wavelength, 14.4J/cm2 for irradiation fluence were the optimal parameters to selectively eliminate promyelocytic leukemia cell HL60 by ALA based PDT. The photosensitization of ALA based PDT caused the necrosis of HL60 cell, so it could be used for inactivation of certain leukemia cells.

Result of Photodynamic Therapy for Idiopathic Subfoveal Choroidal Neovascularization

PURPOSE: To investigate the factors that affect final vision following photodynamic therapy (PDT) for idiopathic subfoveal choroidal neovascularization (CNV). METHODS: A retrospective review of 16 patients whose eyes were diagnosed as idiopathic subfoveal CNV and were followed up for a minimum of 9 months. Statistical analysis was performed to investigate relationships between sex, age, size of the lesion, and initial vision compared to final vision. RESULTS: In the PDT group (10 eyes), the mean age of the patients was 34 years, mean size of the lesion was 1300 micrometer, mean initial vision was 20/60, and 7 of the 10 patients (70%) showed more than a two-line improvement in vision. Factors affecting final vision were sex (p=0.049), initial vision (p=0.0455), and size of the lesion (p=0.006). In the observation group (6 eyes), the mean age of the patients was 39 years, mean size of the lesion was 575 micrometer, mean initial vision was 20/32, and 5 of the 6 patients (83%) showed more than a two-line improvement in vision. CONCLUSIONS: The prognosis of idiopathic CNV was favorable as was reported in other studies. In the PDT group, statistically significant factors affecting final vision were initial vision, size of the lesion, and sex. However, since the number of patients sampled was insufficient and the average size of the lesions in the female patients was smaller, the size of the lesion seems to be the most important factor.

Photodynamic Therapy in Practice: A Review of Experiences with Myopic CNV in Korean Patients

PURPOSE: To evaluate the effects of photodynamic therapy with verteporfin on visual acuity and fluorescein angiography in choroidal neovascularization (CNV) associated with pathologic myopia and to determine if this treatment could reproduce the results achieved in the Verteporfin in Photodynamic Therapy (VIP) Trial in Korean patients. METHODS: Forty-two eyes of 39 patients with CNV secondary to pathologic myopia were included. A retrospective review of their clinical records and fluorescein angiography was done. The patients underwent photodynamic therapy with verteporfin and were followed up for more than 6 months after the therapy. The change in best corrected visual acuity (BCVA) and leakage in fluorescein angiography were evaluated. RESULTS: The mean age of the patients was 39.6 and mean follow-up period was 23.5 months. The BCVA of the patients improved in 22 (52.4%) eyes, was unchanged in 13 (30.9%), and worsened in 7 (16.7%). The leakage in fluorescein angiography decreased in 25 (59.5%) eyes. CONCLUSIONS: Photodynamic therapy with verteporfin for myopic CNV in Korean patients appeared to be effective in stabilization of the lesions and improvement of visual acuity.

Photodynamic Therapy of Actinic Keratoses Using 585nm Dye Laser and Variable Lights / 대한피부과학회지

BACKGROUND: Incohorenet lamps or pulsed/continuous wave lasers have effectively been used for photodynamic therapy (PDT). OBJECTIVE: To assess the safety and efficacy of the various light sources, such as halogen, xenon arc, and the 585nm pulsed dye laser, in photodynamic therapy for treatment of actinic keratosis. METHODS: PDT, using 5-aminolaevulinic acid (5-ALA), was used on 18 patients who had been diagnosed with actinic keratoses. A single treatment consisting of a topical application of 20% 5-aminolaevulinic acid for 4 hours, followed by halogen, xenon arch lamp and the 585nm pulsed dye laser was administered. RESULTS: Of the 227 lesions, 95/106 (89.6%), 68/77 (88.3%), and 39/44 (88.6%) lesions showed complete response to the halogen lamp, xenon arc lamp, and 595nm dye laser respectively, and 10/106 (9.4%), 9/77 (11.7%), and 5/44 (11.4%) lesions showed partial response to the above, respectively. Only one lesion (1.0%) showed no response to the halogen lamp. In all cases, cosmetic outcome was excellent, and anatomical function was preserved. Topical 5-ALA based PDT is an effective and useful treatment modality for various premalignant diseases, to the halogen lamp, xenon arc lamp, or 585nm pulsed dye laser were used. CONCLUSIONS: Treatment of actinic keratosis with various light sources, following topical application of 5-ALA is effective. However, advantages of the laser treatment may include recovery times, excellent postreatment cosmesis, and high efficacy rate.

Effect of Photodynamic Therapy in Lung Cancer / 결핵및호흡기질환

BACKGROUND: Photodynamic therapy (PDT) involves the use of photosensitizing agents for treatment of malignant disease. PDT is approved by the U.S. Food and Drug Administration for the endobronchial microinvasive nonsmall cell lung cancer and for palliation in patients with obstructing tumors. We report our experience and results of PDT in lung cancer. METHOD:Ten patients with lung cancer who were diagnosed in Chosun university hospital by histologic confirm through bronchoscopy were included between August 2002 and May 2003. The photosensitizer (Photogem(R), Lomonosov institute of Fine Chemical, Russia/ dose 2.0 mg/kg body weight) was injected 48 hours prior to the PDT session. For PDT with the photosensitizer (Photogem(R)), Diode LASER system (Biolitec Inc., Germany, wavelength; 633nm) were used. PDTs were done at 48-72 hours after photogem injection. Follow up bronchoscopy and chest X-ray or thorax computerized tomography were done for evaluate PDT response. RESULTS: 9 of 10 patients with endobronchial obstruction showed partial remission with bronchus opening after PDT. Direct reaction of the tumor to PDT was similar in despite of its localization. It was as follows; edema, hyperemia, in-situ bleeding, fibrin film occurrence. Any other complications such as sunburns of skin, inflammation within the PDT zone were not occurred by the end of the fourth week. CONCLUSION: In the advanced endobronchial disease, PDT has been shown to be useful in treating endobronchial tumors that are causing clinically significant dyspnea or are likely to progress and lead to further clinical complications, such as postobstructive pneumonia.

A Case of Subfoveal Choroidal Neovascularization following Multiple Evanescent White-Dot Syndrome

PURPOSE: We report a case of subfoveal choroidal neovascularization following multiple evanescent white dot syndrome (MEWDS). METHODS: A 28-year-old female patient with vitreous floater and scotoma of her right eye was diagnosed with MEWDS. Fundus examination revealed multiple white dots at midperipheral retina, and a granular appearance of macular, which were nearly subsided at 1 month after her first visit. She complained of a sudden decrease in visual acuity of right eye at 3 months after her initial episode of MEWDS. Fundus examination showed macular hemorrhage with edema. Typical subfoveal choroidal neovascularization with leakage was confirmed by Indocyanine Green Angiography (ICGA), which was treated by photodynamic therapy (PDT). RESULTS: Subfoveal choroidal neovascularization following MEWDS is rare, and this is the first Korean case report.

Photodynamic Effects of Radachlorin(R) on Cervical Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Photodynamic therapy (PDT) is a novel treatment modality, which produces local tissue necrosis with laser light following the prior administration of a photosensitizing agent. Radachlorin(R) has recently been shown to be a promising PDT sensitizer. In order to elucidate the antitumor effects of PDT using Radachlorin(R) on cervical cancer, growth inhibition studies on a HPV-associated tumor cell line, TC-1 cells in vitro and animals with an established TC-1 tumor in vivo were determined. MATERIALS AND METHODS: TC-1 tumor cells were exposed to various concentrations of Radachlorin(R) and PDT, with irradiation of 12.5 or 25 J/cm2 at an irradiance of 20 mW/cm2 using a Won-PDT D662 laser at 662 nm in vitro. C57BL/6 mice with TC-1 tumor were injected with Radachlorin(R) via different routes and treated with PDTin vivo. A growth suppression study was then used to evaluate the effects at various time points after PDT. RESULTS: The results showed that irradiation of TC-1 tumor cells in the presence of Radachlorin(R) induced significant cell growth inhibition. Animals with established TC-1 tumors exhibited significantly smaller tumor sizes over time when treated with Radachlorin(R) and irradiation. CONCLUSION: PDT after the application of Radachlorin(R) appears to be effective against TC-1 tumors both in vitro and in vivo.

Therapeutic Effect of Photodynamic Therapy with Indocyanine Green Dye in the Treatment of Choroidal Neovascularization

PURPOSE: To determine experimentally the effectiveness of photodynamic therapy (PDT) with indocyanine green (ICG) dye in the treatment of choroidal neovascularization. METHODS: Following the creation of choroidal neovascularization in the retina of 18 pigmented rats (36 eyes), and ICG dye injection (10 mg/kg) in 18 of the eyes, the authors performed PDT, at intensity of 60 mW, spot size of 2.0 mm, and duration of 20 seconds within 2 minutes after ICG dye injection. 0ne, 4, 6, and 8 weeks after PDT, the authors examined the retina for any signs of regression through angiogram and light microscope. RESULTS: When authors conducted PDT after injecting ICG dye into pigmented rats, there was no significant damage to retina when the intensity was set at 60mW with duration of 10 or 20 seconds. Choroidal neovascularization was found in 18 eyes after argon laser photocoagulation, and regression of neovascularization was confirmed through angiogram and pathologic examination after PDT was performed with ICG dye. Pathologic views revealed significant fibrosis and fibrinoid necrosis. The control group consisting of 18 eyes in which no diode laser photocoagulation was performed, showed no regression of choroidal neovascularization. CONCLUSIONS: PDT with ICG dye was found to be quite effective in the treatment of choroidal neovascularization.

Photodynamic Treatment for Precancerous Disease / 대한피부과학회지

BACKGROUND: Photodynamic therapy(PDT) is a treatment modality using a photosensitizer, light and oxygen to cause photochemically induced selective cell death. Topical PDT is an effective therapy for nonmalignant skin disease as well as various skin conditions. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of PDT in the treatment of precancerous disease, and to evaluate the serial histopathologic findings after PDT. METHOD: PDT using 5-aminolaevulinic acid(ALA) was performed in 6 patients who had been diagnosed with extramammary Paget's disease, actinic cheilitis, actinic keratosis, Bowen's disease and arsenic keratosis. Histopathologic changes after PDT were evaluated by serial biopsy at pre-PDT and 2, 24, 48 hours, 7days post-PDT. TUNEL staining for detecting apoptotic cells was also performed. Light was administered at a wavelength of 600~800nm. The light intensity was 120mW/cm2 and the light dose ranged from 144J/cm2 to 216J/cm2. RESULT: Five patients showed a complete response at 1 month after the PDT and continued to show a complete response over six months. One patient showed a partial response and surgical intervention including laser ablation or conventional surgical excision has been needed. Early histopathologic changes after PDT were epidermal necrosis, band like dermal infiltration of inflammatory cells and thrombi formation in venules. At seven days after PDT, there was significant disappearance of abnormal cells in epidermis. Apoptotic cells were detected at 2, 24 hours post-PDT specimen and decreased from 48 hours post-PDT. CONCLUSION: PDT using 5-ALA is an effective and useful treatment modality for various precancerous skin tumors.