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Reginald Birngruber

Bio: Reginald Birngruber is an academic researcher from University of Lübeck. The author has contributed to research in topics: Laser & Optical coherence tomography. The author has an hindex of 55, co-authored 321 publications receiving 11167 citations. Previous affiliations of Reginald Birngruber include Air Force Research Laboratory & Massachusetts Eye and Ear Infirmary.


Papers
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Journal ArticleDOI
TL;DR: Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, it is recommended ophthalmologists consider vertEPorfin therapy for treatment of such patients.

529 citations

Journal ArticleDOI
TL;DR: In this article, the authors investigated the partition of laser energy between these channels during breakdown in water, and found that the absorption at the breakdown site first decreases strongly with decreasing pulse duration, but increases again for < 3p s.
Abstract: During optical breakdown, the energy delivered to the sample is either transmitted, reflected, scattered, or ab- sorbed. Pathways for the division of the absorbed energy are the evaporation of the focal volume, the plasma radiation, and the mechanical effects such as shock wave emission and cav- itation. The partition of laser energy between these channels during breakdown in water was investigated for four selected laser parameters typical for intraocular microsurgery ( 6-ns pulses of 1 and 10 mJ focused at an angle of 22 ,a nd30-ps pulses of 50 mJ and 1m Jfocused at 14 ,a ll at1064 nm). Scattering and reflection were found to be small compared to transmission and absorption during optical breakdown. The ratio of the shock wave energy and cavitation bubble energy was approximately constant (between 1.5:1 and 2:1). These results allowed us to perform a more comprehensive study of the influence of pulse duration ( 100 fs- 76 ns )a nd focus- ing angle (4- 32) on the energy partition by measuring only the plasma transmission and the cavitation bubble energy. The bubble energy was used as an indicator for the total amount of mechanical energy. We found that the absorption at the breakdown site first decreases strongly with decreasing pulse duration, but increases again for < 3p s. The conversion of the absorbed energy into mechanical energy is 90% with ns pulses at large focusing angles. It decreases both with de- creasing focusing angle and pulse duration (to < 15 %f or fs pulses). The disruptive character of plasma-mediated laser effects is therefore strongly reduced when ultrashort laser pulses are used.

473 citations

Journal ArticleDOI
TL;DR: OCT is a promising new imaging method for visualization of morphologic changes of superficial layers of the human skin that may be useful for noninvasive diagnosis of bullous skin diseases, skin tumors, and in vivo investigation of pharmacologic effects.
Abstract: Background: Optical coherence tomography (OCT) is a new diagnostic method for tissue characterization. Objective: We investigated normal and pathologic structures in human skin in several locations to evaluate the potential application of this technique to dermatology. Methods: Based on the principle of low-coherence interferometry, cross-sectional images of the human skin can be obtained in vivo with a high spatial resolution of about 15 μm. Within a penetration depth of 0.5 to 1.5 mm, structures of the stratum corneum, the living epidermis, and the papillary dermis can be distinguished. Results: Different layers could be detected that were differentiated by induction of experimental blisters and by comparison with corresponding histologic sections. Furthermore, OCT images of several skin diseases and tumors were obtained. Conclusion: OCT is a promising new imaging method for visualization of morphologic changes of superficial layers of the human skin. It may be useful for noninvasive diagnosis of bullous skin diseases, skin tumors, and in vivo investigation of pharmacologic effects. (J Am Acad Dermatol 1997;37:958-63.)

429 citations

Journal ArticleDOI
TL;DR: Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 of 31 patients, and this strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT.
Abstract: OBJECTIVES: To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. DESIGN: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m2 infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm2 applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm2 applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. RESULTS: The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, -5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented regularly at 1 week after each retreatment. Fluorescein leakage reappeared by 4 to 12 weeks after a retreatment in almost all cases. However, compared with baseline, leakage activity appeared to be reduced after multiple PDT courses. For the 31 patients who had follow-up for 3 months after the last retreatment and had received retreatment 2 to 4 weeks after the initial treatment, progression of CNV beyond the area identified before the retreatment was noted in 10 (48%) of the 21 eyes with classic CNV in regimen 2 and 9 (90%) of 10 eyes in regimen 4. The rate and severity of ocular or systemic adverse events were not increased by multiple applications. CONCLUSIONS: Multiple applications of PDT with verteporfin achieve repetitive, short-term cessation of fluorescein leakage from CNV secondary to AMD, without loss of visual acuity. This strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT for recurrent fluorescein dye leakage from persistent or recurrent CNV, following an initial or subsequent PDT treatment, with maintenance of visual acuity. Retreatments may achieve progressive cessation of leakage and prevent further growth of CNV and subsequent visual loss.

373 citations

Journal ArticleDOI
TL;DR: Compared with photocoagulation BPD-PDT allows endothelial-bound intraluminal photothrombosis, sparing important structures such as neural retina and Bruch's membrane, and may provide a more selective treatment of juxtafoveal and subfoveal neovascular membranes.

256 citations


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Journal Article
TL;DR: In this article, a fast Fourier transform method of topography and interferometry is proposed to discriminate between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour generation techniques.
Abstract: A fast-Fourier-transform method of topography and interferometry is proposed. By computer processing of a noncontour type of fringe pattern, automatic discrimination is achieved between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour-generation techniques. The method has advantages over moire topography and conventional fringe-contour interferometry in both accuracy and sensitivity. Unlike fringe-scanning techniques, the method is easy to apply because it uses no moving components.

3,742 citations

Journal ArticleDOI
TL;DR: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin (Visudyne) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration (AMD).
Abstract: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD).

2,098 citations

Journal ArticleDOI
TL;DR: The basic premise of this review is that a combination of imaging and PDT will provide improved research and therapeutic strategies.
Abstract: 1.1 Photodynamic Therapy and Imaging The purpose of this review is to present the current state of the role of imaging in photodynamic therapy (PDT). In order for the reader to fully appreciate the context of the discussions embodied in this article we begin with an overview of the PDT process, starting with a brief historical perspective followed by detailed discussions of specific applications of imaging in PDT. Each section starts with an overview of the specific topic and, where appropriate, ends with summary and future directions. The review closes with the authors’ perspective of the areas of future emphasis and promise. The basic premise of this review is that a combination of imaging and PDT will provide improved research and therapeutic strategies. PDT is a photochemistry-based approach that uses a light-activatable chemical, termed a photosensitizer (PS), and light of an appropriate wavelength, to impart cytotoxicity via the generation of reactive molecular species (Figure 1a). In clinical settings, the PS is typically administered intravenously or topically, followed by illumination using a light delivery system suitable for the anatomical site being treated (Figure 1b). The time delay, often referred to as drug-light interval, between PS administration and the start of illumination with currently used PSs varies from 5 minutes to 24 hours or more depending on the specific PS and the target disease. Strictly speaking, this should be referred to as the PS-light interval, as at the concentrations typically used the PS is not a drug, but the drug-light interval terminology seems to be used fairly frequently. Typically, the useful range of wavelengths for therapeutic activation of the PS is 600 to 800 nm, to avoid interference by endogenous chromophores within the body, and yet maintain the energetics necessary for the generation of cytotoxic species (as discussed below) such as singlet oxygen (1O2). However, it is important to note that photosensitizers can also serve as fluorescence imaging agents for which activation with light in the 400nm range is often used and has been extremely useful in diagnostic imaging applications as described extensively in Section 2 of this review. The obvious limitation of short wavelength excitation is the lack of tissue penetration so that the volumes that are probed under these conditions are relatively shallow. Open in a separate window Figure 1 (A) A schematic representation of PDT where PS is a photoactivatable multifunctional agent, which, upon light activation can serve as both an imaging agent and a therapeutic agent. (B) A schematic representation of the sequence of administration, localization and light activation of the PS for PDT or fluorescence imaging. Typically the PS is delivered systemically and allowed to circulate for an appropriate time interval (the “drug-light interval”), during which the PS accumulates preferentially in the target lesion(s) prior to light activation. In the idealized depiction here the PS is accumulation is shown to be entirely in the target tissue, however, even if this is not the case, light delivery confers a second layer of selectivity so that the cytotoxic effect will be generated only in regions where both drug and light are present. Upon localization of the PS, light activation will result in fluorescence emission which can be implemented for imaging applications, as well as generation cytotoxic species for therapy. In the former case light activation is achieved with a low fluence rate to generate fluorescence emission with little or no cytotoxic effect, while in the latter case a high fluence rate is used to generate a sufficient concentration of cytotoxic species to achieve biological effects.

1,922 citations

Journal ArticleDOI
TL;DR: OCT as discussed by the authors synthesises cross-sectional images from a series of laterally adjacent depth-scans, which can be used to assess tissue and cell function and morphology in situ.
Abstract: There have been three basic approaches to optical tomography since the early 1980s: diffraction tomography, diffuse optical tomography and optical coherence tomography (OCT). Optical techniques are of particular importance in the medical field, because these techniques promise to be safe and cheap and, in addition, offer a therapeutic potential. Advances in OCT technology have made it possible to apply OCT in a wide variety of applications but medical applications are still dominating. Specific advantages of OCT are its high depth and transversal resolution, the fact, that its depth resolution is decoupled from transverse resolution, high probing depth in scattering media, contact-free and non-invasive operation, and the possibility to create various function dependent image contrasting methods. This report presents the principles of OCT and the state of important OCT applications. OCT synthesises cross-sectional images from a series of laterally adjacent depth-scans. At present OCT is used in three different fields of optical imaging, in macroscopic imaging of structures which can be seen by the naked eye or using weak magnifications, in microscopic imaging using magnifications up to the classical limit of microscopic resolution and in endoscopic imaging, using low and medium magnification. First, OCT techniques, like the reflectometry technique and the dual beam technique were based on time-domain low coherence interferometry depth-scans. Later, Fourier-domain techniques have been developed and led to new imaging schemes. Recently developed parallel OCT schemes eliminate the need for lateral scanning and, therefore, dramatically increase the imaging rate. These schemes use CCD cameras and CMOS detector arrays as photodetectors. Video-rate three-dimensional OCT pictures have been obtained. Modifying interference microscopy techniques has led to high-resolution optical coherence microscopy that achieved sub-micrometre resolution. This report is concluded with a short presentation of important OCT applications. Ophthalmology is, due to the transparent ocular structures, still the main field of OCT application. The first commercial instrument too has been introduced for ophthalmic diagnostics (Carl Zeiss Meditec AG). Advances in using near-infrared light, however, opened the path for OCT imaging in strongly scattering tissues. Today, optical in vivo biopsy is one of the most challenging fields of OCT application. High resolution, high penetration depth, and its potential for functional imaging attribute to OCT an optical biopsy quality, which can be used to assess tissue and cell function and morphology in situ. OCT can already clarify the relevant architectural tissue morphology. For many diseases, however, including cancer in its early stages, higher resolution is necessary. New broad-bandwidth light sources, like photonic crystal fibres and superfluorescent fibre sources, and new contrasting techniques, give access to new sample properties and unmatched sensitivity and resolution.

1,914 citations

Journal ArticleDOI
TL;DR: It was found that the structure and morphology also affect the energy transport among tissue constituents and therefore the ablation efficiency of biological tissues is increased.
Abstract: Author(s): Vogel, Alfred; Venugopalan, Vasan | Abstract: The mechanisms of pulsed laser ablation of biological tissues were studied. The transiently empty space created between the fiber tip and the tissue surface improved the optical transmission to the target and thus increased the ablation efficiency. It was found that the structure and morphology also affect the energy transport among tissue constituents.

1,861 citations