Course Of Photodynamic Therapy Research Articles

Comparative study for the effect of photodynamic therapy, imiquimod immunotherapy and combination of both therapies on 40 lesions of actinic keratosis in Japanese patients

We treated 12, 15 and 13 Japanese actinic keratosis (AK) lesions with 5-aminolevulinic acid photodynamic therapy (PDT), 5% imiquimod cream and combination of both therapies, respectively, and compared the effects. Patients underwent the second course, when AK lesions remained after the first course. Efficacy was evaluated 1month after each treatment. Combination therapy cleared all AK lesions only after the first course, while PDT and imiquimod therapy cleared 41.7% and 66.7% of AK lesions after the first course, respectively. All residual AK lesions after the first course were cleared by the second courses of PDT or imiquimod therapy. During the course, erosion and crust developed significantly more frequently in combination therapy (P<0.001). Most Japanese AK lesions can be satisfactorily treated with either PDT or imiquimod monotherapy. However, only severe cases may better be treated with combination therapy, which show higher efficacy even though adverse events occur frequently.

Nitrosylhemoglobin in photodynamically stressed human tumors growing in nude mice

The role of nitric oxide in human tumor biology and therapy has been the subject of extensive studies. However, there is only limited knowledge about the mechanisms of NO production and its metabolism, and about the role NO can play in modern therapeutic procedures, such as photodynamic therapy. Here, for the first time, we report the presence of nitrosylhemoglobin, a stable complex of NO, in human lung adenocarcinoma A549 tumors growing in situ in nude mice. Using electron paramagnetic resonance spectroscopy we show that the level of nitrosylhemoglobin increases in the course of photodynamic therapy and that the phenomenon is local. Even the destruction of strongly vascularized normal liver tissue did not induce the paramagnetic signal, despite bringing about tissue necrosis. We conclude that photodynamic stress substantiates NO production and blood extravasation in situ, both processes on-going even in non-treated tumors, although at a lower intensity.

Fertility Preservation via Photodynamic Therapy in Young Patients With Early-Stage Uterine Endometrial Cancer

We evaluated the effectiveness of photodynamic therapy (PDT) as a conservative fertility-sparing treatment in young women with early-stage endometrial cancer. We reviewed the medical records of patients with endometrial cancer who had been treated with PDT. Of the patients with endometrioid adenocarcinoma, we included those younger than 35 years and in whom the lesion was confined to the endometrium. Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine endometrial cavity and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. Complete response was pathologically defined as the complete disappearance of adenocarcinoma or hyperplastic tissue. Sixteen patients were included in the study. Their mean age was 30.7 years, and the mean body mass index was 24.6 kg/m(2). The mean follow-up period was 78 months. Photodynamic therapy was used in 11 patients as primary treatment and in 5 patients as secondary treatment for recurrence after primary hormonal therapy. Complete remission was observed in 12 (75%) of the 16 patients. Of these 12 patients, 4 experienced recurrence (33%). Two of the 4 patients who experienced recurrence showed complete remission after the next course of PDT, and 1 of the 4 nonresponders also showed complete remission after the second course of PDT. The final response rate was therefore 68%. Of the 7 women who attempted to get pregnant, 4 had 7 successful pregnancies (57%, 4/7), resulting in 6 live births. No tumor-related deaths or PDT-related severe adverse effects were noted. Photodynamic therapy can be an effective conservative treatment method for fertility sparing in young patients with early-stage endometrial adenocarcinoma.

New optional photodynamic therapy laser wavelength for infantile port wine stains: 457 nm

To expand the optional laser wavelengths of photodynamic therapy (PDT) for port wine stain (PWS), the feasibility of applying a 457 nm laser to the PDT for infantile PWS was analyzed by mathematical simulation and was validated by clinical experiment. Singlet oxygen yield of 457 nm PDT or 532 nm PDT in an infantile PWS model and an adult PWS model was theoretically simulated. Fifteen PWS patients (14 infants and 1 adult) with 40 spots were treated with 457 nm (20 spots) and 532 nm (20 spots), respectively, in two PDT courses. Simulation results showed that under the same power density and irradiation time, singlet oxygen yield of 457 nm PDT and 532 nm PDT are similar in infantile PWS vessels. Yet, in adult PWS vessels, singlet oxygen yield of 457 nm PDT is lower than 532 nm PDT. Clinical outcomes showed that no statistic difference existed between 457 nm PDT and 532 nm PDT for infantile PWS. The result of this study suggested that 457 nm wavelength laser has the potential to be applied in PDT for infantile PWS.

PDT in non‐surgical treatment of periodontitis in HIV patients: A split‐mouth, randomized clinical trial

The aim of this study was to evaluate the clinical and microbiological effect of photodynamic therapy (PDT) in the non-surgical treatment of periodontitis in HIV patients. Twelve HIV patients from the CEAPE/UNIP, Brazil, with periodontitis were included in this 6-month, split-mouth, double-blind, controlled clinical trial. Patients were placed in the following groups: Group SRP-scaling and root planning with an ultrasonic device (SRP); and Group SRP + PDT-SRP associated with a course of PDT with a diode laser with a wavelength of 660 nm and 0.03 W power associated with methylene blue 0.01% lasting 133 seconds. All clinical measurements (periodontal probing depth (PPD), gingival recession (GR), clinical attachment level (CAL), full-mouth plaque index (FMPI), bleeding score (FMBS)), and microbiological parameters (detection of Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), and Aggregatibacter actinomycetemcomitans (Aa)) were assessed at baseline and at 45 days, and 3 and 6 months after therapy. The ANOVA/Tukey was used for statistical analysis (α = 5%). There were no differences in any of the investigated parameters observed at baseline in the two groups (P > 0.05). Moreover, participants in the SRP + PDT group presented a higher PPD reduction and CAL gain than those in the SRP group at 45 days and 3 and 6 months. At 6 months, sites receiving SRP + PDT showed a significant PPD reduction of 1.4 ± 0.5 mm, while those in the SRP group showed a 0.3 ± 0.8 mm reduction (P < 0.05). The CAL gain at the sixth month was 1.3 ± 0.5 mm and 0.2 ± 0.7 mm for participants in the SRP + PDT and SRP groups, respectively (P < 0.05). Microbiologically, both therapies presented a reduction in the detection of Pg, Tf, and Aa, and there was no difference between them (P > 0.05). We concluded that PDT therapy used adjunctively to SRP could promote additional benefits in the treatment of HIV-associated periodontitis.

Dose characteristics of radachlorin photosensitizer in modeling the photodynamic effect on the cellular level

A study was carried out on the dose characteristics of the Radachlorin photosensitizer using both a laser light source and partially coherent irradiation from a matrix light-emitting diode observing the photodynamic effect on an erythrocyte suspension at various concentrations. The use of these results is proposed for developing a procedure for the a priori determination of irradiation dose for specific patients in the course of photodynamic therapy.

Fluorescence examination and photodynamic therapy of facial squamous cell carcinoma—A case report

To evaluate the usefulness and feasibility of fluorescence examination and photodynamic therapy (PDT) for facial squamous cell carcinoma. A 68-year-old male patient underwent 3 courses of PDT. The first treatment was carried out using topically applied 5-aminolevulinic acid (ALA) to the affected area (5.0 cm × 2.5 cm) 3h before light irradiation. ALA/PpIX-mediated fluorescence was used to visualize the lesion and its margin. The lesion was illuminated with a 630 nm laser at 120 J/cm². Thirty days later, the residual lesion received the second treatment at the same light dose after topical use of ALA. Despite the tumor was treated with two courses of PDT, The lesion was not cleared completely yet. At last we used topical ALA and intravenous injection of HiPorfin, with the same light dose, then the lesion was cured and the patient was tumor-free followed up for over 15 months. ALA/PpIX-mediated fluorescence visualized the lesion location. Complete cure was achieved after the third course of ALA/Hiporfin PDT. During the 15 months of followed up, no recurrence was noticed. ALA assisted fluorescence examination can be a useful tool to visualize the malignant lesion and determine its margin. ALA-PDT is effective for superficial lesions, but for thicker and deeper lesions, systemic administration of photosensitizer is indispensable.

Traitement de la maladie de Paget extramammaire par photothérapie dynamique topique

The usual treatment for extramammary Paget's disease (EMPD) is surgery, but this approach may have grave functional and physical consequences, as well as high recurrence rates. Topical photodynamic therapy (PDT) offers an optional approach for EMPD; it has a high complete response rate and there is no dose restriction. The aim of this study was to evaluate the efficacy and safety of PDT in the treatment of EMPD. This series of patients was seen at a single centre between 1 December 2005 and 31 December 2010. All patients with histologically confirmed EMPD were included. Patients received two courses of PDT 21 days apart: 3 hours after topical application of methyl aminolevulinic acid emulsion, they underwent illumination with red light (570-670 nm) at a dose of 37 J/cm(2) for 10 minutes. In the event of relapse, a further cycle was given at week 6. Eight patients (seven female, one male) of a mean age of 69 years were included. After two series of two illuminations, seven patients were in complete clinical remission at 3 months and one patient was in partial remission. Five patients were still in complete clinical remission at 6 months. All patients had relapsed after a mean 8.4 months (4-14 months). The limiting factor appears to be pain occurring during illumination. Patients reported satisfaction with the disappearance of symptoms and a notable improvement in quality of life. The complete clinical response rate to PDT at month 6, after two series of two illuminations, was equivalent to that for surgery. Although the recurrence rate was high, this treatment may be repeated without functional or physical consequences. PDT resulted in disappearance of pain and improved quality of life.

Combined photodynamic and low-level laser therapies as an adjunct to nonsurgical treatment of chronic periodontitis

In recent years, there has been a growing interest in the use of dental lasers for treatment of periodontal diseases. The purpose of this short-term clinical trial was to evaluate the effects of a combination of photodynamic therapy with low-level laser therapy as an adjunct to nonsurgical treatment of chronic periodontitis. Twenty-four nonsmoking adults with untreated chronic periodontitis were randomly assigned in a split-mouth design to receive scaling and root debridement with or without one course of adjunctive photodynamic therapy and low-level laser therapy within 5 d. Plaque, bleeding on probing, probing depth and gingival recession were recorded at baseline, 1 and 3 mo after the treatment. Gingival crevicular fluid was collected for assay of interleukin-1β levels at baseline, 1 wk and 1 mo. The test teeth achieved greater reductions in the percentage of sites with bleeding on probing and in mean probing depth at 1 mo compared with the control teeth (p < 0.05). A significant decrease in gingival crevicular fluid volume was observed in both groups at 1 wk (p < 0.001), with a further decrease at 1 mo in the test sites (p < 0.05). The test sites showed a greater reduction of interleukin-1β levels in gingival crevicular fluid at 1 wk than the control sites (p < 0.05). No significant differences in periodontal parameters were found between the test and control teeth at 3 mo. The present study suggests that a combined course of photodynamic therapy with low-level laser therapy could be a beneficial adjunct to nonsurgical treatment of chronic periodontitis on a short-term basis. Further studies are required to assess the long-term effectiveness of the combination of photodynamic therapy with low-level laser therapy as an adjunct in nonsurgical treatment of periodontitis.

Effects of photodynamic therapy with verteporfin for the treatment of chronic central serous chorioretinopathy: An uncontrolled, open-label, observational study

Background: Central serous chorioretinopathy is an idiopathic disorder that leads to serous neurosensory retinal detachment. The disorder is usually self-limited and resolves spontaneously; however, sometimes neurosensory retinal detachment persists. This form of the disorder is called chronic central serous chorioretinopathy (CCSC). Objective: The aim of this study was to assess the effects of photodynamic therapy (PDT) on visual acuity with full-dose verteporfin for CCSC. Methods: The eyes of patients with CCSC were included in the study. Ophthalmic examination including best-corrected visual acuity (BCVA), fundus examination, fluorescein angiography, and optical coherence tomography was performed before treatment and at 1, 3, 6, 9, and 12 months. PDT with full-dose verteporfin (6 μ/m 2 of body surface area) was applied only to areas of active leakage. BCVA was converted to a log of the minimum angle of resolution (logMAR) equivalent for statistical analysis. Central foveal thickness and BCVA between baseline and follow-up were compared. Results: Seventeen eyes of 16 patients (13 males, 3 females; mean [SD] age, 39.75 [7.51] years; mean duration of follow-up, 13.06 [1.82] months) were used in the study. The mean (SEM) logMAR BCVA was 0.26 (0.07) at baseline and 0.04 (0.02) at 12 months. Mean logMAR BCVA values at baseline (0.259) and after treatment (0.112, 0.053, 0.047, 0.041, and 0.041 at 1, 3, 6, 9, and 12 months, respectively) differed significantly ( P = 0.006, P = 0.005, P = 0.005, P = 0.005, and P = 0.005). There was a significant difference in the mean central foveal thickness at the final visit (169 μm) compared with the baseline value (383 μm; P < 0.001). BCVA decreased in one eye (20/20 vs 20/25) and persisted during follow-up; in the other 16 eyes, BCVA either increased (n = 10) or remained stable (n = 6). Conclusions: In this small, open-label study, patients with CCSC treated with a single course of PDT with full-dose verteporfin had significant improvement from baseline in BCVA and resolution of subretinal fluid accumulation and active leakage. Treatment was generally well tolerated, but one patient had worsening in BCVA.

Lipophilic photosensitizer administration via the prostate arteries for photodynamic therapy of the canine prostate

Current limitations of interstitial photodynamic therapy (PDT) for treatment of prostate cancer include low drug selectivity after intravenous (i.v.) administration and incomplete ablation of glandular tissue. To overcome these limitations, intra-arterial (i.a.) injection of a photosensitizer was tested in a canine model. A lipophilic photosensitizer, SL052 formulated in liposomes or dissolved in dimethyl sulphoxide (DMSO), was injected into male dogs as an intravenous injection or intra-arterially via the prostate arteries. Optical fibers were inserted into the prostate 3h after i.v. or immediately following i.a. drug delivery. Laser light was delivered through the fibers in cycles controlled by a computer-driven switch. Drug concentration (fluorescence) and light transmission in prostate tissue were monitored during the course of PDT. Side effect profile and completeness of prostate gland ablation were the primary parameters compared among treatment groups. Control animals received drug-only or light-only treatment. Thirteen dogs were treated by PDT mediated by i.a. injection of SL052 dissolved in DMSO and attained either complete ablation of prostatic glandular tissue or significant reduction of prostate volume compared with that of pre-PDT (p<0.0001). When compared to i.v. administration the i.a. route resulted in more complete photo-ablation. Associated side effect included acute urinary retention which resolved overtime. No incontinence was observed. With careful tailoring of PDT drug and light doses, interstitial PDT with i.a. injection of SL052-DMSO has the potential to provide effective treatment for prostate disease.

Topical ALA PDT for the treatment of severe acne vulgaris

To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)-medicated photodynamic therapy (PDT) for the treatment of severe acne vulgaris. A total of 78 Chinese patients with Grade 4 severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (10%) was applied topically to acne lesions for 3 h. The lesions were irradiated by a LED light of 633 nm at dose levels of 50-70 J/cm(2) at 66 mW/cm(2). Clinical assessment was conducted before and after treatment up to 6 months. 22% of patients showed excellent improvement after one-course treatment and another 34% showed excellent improvement after two-course. The rest (44%) required three-course treatment to further reduce the number and size of residual lesions. Adverse effects were minimal. The symptoms and signs in recurrent cases (14%) were much milder and responded well to conventional topical medication. ALA PDT is a simple, safe and effective therapeutic option for the treatment of severe acne. Further studies to fully understand its mechanisms and optimize its effectiveness are needed.

Treatment of perianal Paget’s disease using photodynamic therapy with assistance of fluorescence examination: case report

Our aim was to determine the usefulness of fluorescence examination and photodynamic therapy (PDT) for the management of perianal extramammary Paget's disease. A 75-year-old woman underwent two courses of PDT. The first treatment was carried out with topically applied 5-aminolevulinic acid (ALA) to the affected area (2.5 x 2.5 cm(2)) 3 h before light treatment. We used ALA/protoporphyrin IX (PpIX)-mediated fluorescence to visualize the lesion and its margins. The lesion was treated with a 630 nm laser at 120 J/cm(2). Forty days later, the residual lesion was given a second treatment at the same light dose after topical application of ALA and intravenous injection of HiPorfin. ALA/PpIX-mediated fluorescence served as a useful tool to visualize the lesion's location. Complete cure was achieved after the second course of PDT. During 7 months of follow up, no recurrence, scarring or functional loss was noticed. We concluded that ALA-assisted fluorescence examination can be a useful tool to determine the lesion and its margins. ALA-PDT is effective for superficial lesions, but, for thicker and deeper lesions, the systemic administration of photosensitizer is needed.

Estimation of blood microcirculation in integuments by non-invasive speckle-optical method under the photodynamic action

In studies on animals (rats, rabbits) an experimental technique for estimation of microhemocirculation parameters of tissue under treatment has been developed. This technique has been used to compare the changes of speckle-optical parameters of skin microhemodynamics in laser-irradiated and light-isolated areas in the course of photodynamic therapy. Strong correlation between efficiency of tissue response and injection-photoirradiation time interval has been established. The results obtained are confirmed by the data of microhemodynamics estimation in the course of photodynamic therapy by the method of intravital microscopy. The defined ways of modification of the speckle-optical module will make it possible to optimize the conditions of parameters registration taking into account the object features and to improve informativity and sensitivity of the method.

The use of magnetic field effects on photosensitizer luminescence as a novel probe for optical monitoring of oxygen in photodynamic therapy

The effect of a magnetic field on the steady-state and time-resolved optical emission of a custom fullerene-linked photosensitizer (PS) in liposome cell phantoms was studied at various oxygen concentrations (0.19–190 µM). Zeeman splitting of the triplet state and hyperfine coupling, which control intersystem crossing between singlet and triplet states, are altered in the presence of low magnetic fields (B < 320 mT), perturbing the luminescence intensity and lifetime as compared to the triplet state at B = 0. Measurements of the luminescence intensity and lifetime were performed using a time-domain apparatus integrated with a magnet. We propose that by probing magnet-affected optical emissions, one can monitor the state of oxygenation throughout the course of photodynamic therapy. Since the magnetic field effect (MFE) operates primarily by affecting the radical ion pairs related to type I photodynamic action, the enhancement or suppression of the MFE can be used as a measure of the dynamic equilibrium between the type I and II photodynamic pathways. The unique photo-initiated charge-transfer properties of the PS used in this study allow it to serve as both cytotoxic agent and oxygen probe that can provide in situ dosimetric information at close to real time.

Patient Predictors of Esophageal Stricture Development After Photodynamic Therapy

The most common significant adverse event after photodynamic therapy (PDT) with porfimer sodium is esophageal stricture formation. This study assessed whether pretreatment variables, including prior endoscopic therapy for Barrett's esophagus, are associated with post-PDT stricturing. Data from all patients who had undergone PDT with porfimer sodium for Barrett's esophagus with high-grade dysplasia, intramucosal carcinoma, or T1 cancer at our institution since 1997 were reviewed. One hundred sixteen patients underwent 160 courses of PDT. The incidence of stricture formation after index PDT was 16% (19/116). For all PDT courses, the overall incidence of stricture was 23% (37/160). Stricture rate was significantly higher after a second PDT course compared with index PDT (43% vs 16%, P = .0007). There was no association between post-PDT stricture development and age, gender, body mass index, or prior endoscopic mucosal resection. Patients who developed a stricture had a longer length of Barrett's esophagus before treatment than those who did not develop a stricture (7.7 vs 5.7 cm for index PDT only, P = .025; 7.4 vs 5.7 cm for all PDT courses, P = .007). Length of Barrett's esophagus, multiple PDT courses, and presence of intramucosal carcinoma on pretreatment pathology were independent predictors of post-PDT stricture in a stepwise logistic regression analysis controlling for treatment variables, including treatment length. An increased risk of stricture development was seen after multiple courses of PDT. An association between post-PDT stricture and length of Barrett's esophagus but not treatment length was also found. Endoscopic mucosal resection did not appear to influence the likelihood of stricture development after porfimer sodium-based PDT.

Photodynamic Therapy Treatment for Eyes with Drusenoid Pigment Epithelium Detachment

We report the clinical course of photodynamic therapy (PDT) in a patient with drusenoid pigment epithelium detachment (PED). A patient with drusenoid PED underwent PDT follow-up was carried out at one week, one month, three months, six months and one year after treatment. Fundus exam, optical coherence tomography (OCT) and fluorescein angiography were performed. After the PDT, drusen and PED were gradually diminished over one year. However, pure serous PED eventually developed at the same location of the drusenoid PED. The results of the PDT, on drusenoid PED, were initially effective, but not completely successful. Therefore, PDT may be considered as an alternative treatment option for drusenoid PED.

Deficits in the electroretinogram in neovascular age-related macular degeneration and changes during photodynamic therapy

To describe the deficits in four electroretinography (ERG) modalities in patients with neovascular age-related macular degeneration (AMD). To describe the changes in these parameters during a course of verteporfin photodynamic therapy (PDT). Pattern (PERG), multifocal (mfERG) (19 segment simplified test protocol), flash ERG and flicker ERG were performed in patients with active neovascular AMD before PDT and compared to fellow eye controls using paired t-tests. Changes in ERG parameters during the 12 month treatment course were visualised using 95% confidence intervals of the median difference. The statistical significance of any changes was quantified using Wilcoxon signed ranks tests. Fifty patients were recruited and followed. At presentation all ERG amplitudes were reduced with greater reductions in focal as opposed to global test protocols (P < 0.05). Over the 12 month course of PDT, PERG P50 amplitude showed a general downward trend and latency remained unchanged. mfERG p1 amplitude density showed an upward trend at six months before returning to baseline by 12 months. mfERG ring 2 amplitude density was significantly increased at 12 months compared to baseline (P = 0.010). Flicker ERG latency was significantly increased at six months compared to baseline (P = 0.015). The simplified mfERG protocol was tolerated by this patient group, however, they found the full test protocol demanding. Large deficits in the retinal ERG function occur in neovascular AMD and involve retinal locations adjacent to as well as overlying choroidal neovascularisation (CNV). After PDT there is an improvement in electro-retinal function in retinal locations overlying the CNV.

Pre-Treatment Predictors of Esophageal Stricture Formation Following Photodynamic Therapy for Barrett's Esophagus with High-Grade Dysplasia

Introduction: The major local adverse effect of photodynamic therapy (PDT) with porfimer sodium is esophageal stricture formation. The exact cause of stricture formation is not known but might be influenced by treatment variables including treatment length, light dosimetry and use of a centering balloon. This study was performed to assess whether pre-treatment variables, including prior endoscopic therapy for Barrett's esophagus (BE), are associated with post-PDT stricture formation. Methods: Data were reviewed for all patients who have undergone PDT with porfimer sodium for BE with high-grade dysplasia at our institution since 1997. Exclusion criteria included palliative PDT for adenocarcinoma stage T2 or greater and PDT for squamous cell carcinoma. Results: 113 patients underwent 158 PDT courses (75 patients treated with a single PDT course, 32 patients with 2 courses, 5 patients with 3 courses, and 1 patient with 4 courses). 81% were male and 99% were Caucasian, with a mean age of 70.3 at the time of index PDT. 83% of patients received additional endoscopic treatment for BE, including 28 who underwent endoscopic mucosal resection (EMR) prior to PDT. The incidence of stricture formation following index PDT was 15% (17/113). When all PDT courses were considered, the overall incidence of stricture was 23% (36/158). Stricture rate was significantly higher following a second PDT course compared with index PDT (45% versus 15%, [P = 0.0002]). Of the 17 patients who developed stricture following index PDT, 6 underwent a second PDT course, with 3 developing recurrent stricture. There was no association between age, gender, or body-mass index and development of post-PDT stricture. There was no association between prior EMR and post-PDT stricture. Patients who developed stricture had longer length BE pre-treatment than those who did not develop stricture (8.3 cm versus 5.7 cm [P = 0.005] for index PDT only; 7.5 cm versus 5.7 cm [P = 0.004] for all PDT courses). Length of BE and multiple PDT courses were independent predictors of post-PDT stricture in a stepwise logistic regression analysis controlling for treatment variables, including treatment length. Conclusions: Endoscopic therapy for BE frequently requires multiple courses of PDT or PDT as one component in a multimodality approach. EMR has gained use as a neoadjuvant therapy, and does not appear to influence the likelihood of stricture development following porfimer sodium PDT. Our data demonstrate an increased risk of stricture following multiple PDT courses. Our data also suggest an association between post-PDT stricture and length of BE, but not treatment length.

Neurotrophic Factors Minimize the Retinal Toxicity of Verteporfin Photodynamic Therapy

A prior study showed that brain-derived neurotrophic factor (BDNF) rescues photoreceptors from collateral retinal damage caused by photodynamic therapy (PDT). This study was conducted to determine whether ciliary neurotrophic factor (CNTF), a combination of BDNF and CNTF, or pigment epithelial cell-derived growth factor (PEDF) might protect photoreceptors and retinal function more effectively than BDNF. Also investigated was whether protection would be observed after a second round of PDT with adjunctive BDNF treatment. Normal rats received intravitreal injections of BDNF, CNTF, a combination of BDNF and CNTF, or PEDF in one eye and PBS in the other 2 days before PDT. Retinal function and photoreceptor survival were assessed with multifocal ERG (mfERG) and histology 1 week after PDT. Another group of rats received two courses of PDT 3 months apart, with injection of BDNF 2 days before each treatment. All factors significantly increased photoreceptor survival. The combination of BDNF and CNTF rescued more photoreceptors than either factor alone. Only BDNF improved retinal function 1 week after PDT, with CNTF and the combination of BDNF and CNTF reducing mfERG responses. BDNF injection before a second round of PDT improved mfERG responses and retinal structure. BDNF is the most effective single factor among those tested for neuroprotection and improvement of retinal function after PDT, although a combination of BDNF and CNTF rescues more photoreceptors. Adjunctive treatment with BDNF also protects retinal structure and function through two rounds of PDT, suggesting its potential value for patients who require multiple treatments.