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Biomedical subjects

R Birngruber

Publications and source records attributed to R Birngruber.

At least 73 records · Page 4Linked to original sources

Development of a new Er: YAG laser conception for laser sclerostomy ab externo: experimental and first clinical results.

The erbium:YAG laser is a preferable energy source for laser sclerostomy ab externo due to the high absorption of its radiation (2940-nm wavelength) in the aqueous parts of scleral tissue. It has thus far been a disadvantage that laser energy has to be transmitted from the laser source to the application site via very susceptible special optical fibers (ZrF). As a consequence of technical improvements, the laser source could be integrated into the application probe. Therefore, only a robust quartz fiber was necessary for contact application. A fiber diameter of 400 microns was chosen according to the experience gained in previous studies. A total of 24 eyes with chronical open-angle glaucoma were treated. A fistula end-point detection unit was developed for safe indication of a full-thickness perforation of the sclera. With a fiber diameter of 400 microns, a postoperative success rate of about 54% was achieved at 6 months follow-up. The automated full-thickness perforation detection prevented the application of additional, surplus laser pulses in the anterior chamber. The postoperative success rate could be improved over that achieved in previous studies. The new device/conception offers more technical reliability and is a further step toward minimally invasive fistulating laser surgery of open-angle glaucoma.

Erbium↗

[Progress in laser sclerotomy ab externo] Enlarging the sclerostomy channel and local mitomycin administration].

In a previous study we presented our first results after sclerostomy using a pulsed erbium/holmium: YAG laser. At a fiber diameter of 300 microns a success rate of 20-30% was found after a 1-year follow-up. This study concentrates on the improvement of the parameters for filter survival. METHODS. The fiber diameter and thus the size of the fistula increased to 400 microns. Patients who had undergone fibrosis for a previous fistula were treated intraoperatively with topical mitomycin administration. RESULTS. After a follow-up of 6 months, filter function in the 300 microns group was maintained in 26% of the treated eyes (n = 23), while 400 microns fistulas were successful in 48% (n = 26). In the mitomycin-treated group (n = 6), sclerostomy achieved an IOP regulation in four patients. Postoperative hypotony was more frequent, but did not exceed 2 weeks. CONCLUSION. An increase in fistula diameter improves the long-term results of laser sclerostomy. Mitomycin is useful in maintaining filter function in patients with an unfavorable prognosis.

Antibiotics, Antineoplastic↗

Laser sclerostomy ab externo using two different infrared lasers: a clinical comparison.

This study was designed to compare the clinical results of an ab externo approach to laser sclerostomy using two different laser sources under identical conditions. A pulsed (200 microseconds) erbium-YAG laser (lambda = 2940 nm) and a pulsed (200 microseconds) holmium:YAG laser (lambda = 2120 nm) were used. The energy of each laser was transmitted via a fiber (300 microns in diameter) and applied near the limbus, with the fiber tip remaining in steady contact with the sclera. According to the higher tissue absorption coefficient, a shorter penetration depth and, therefore, fewer complications were expected for the Er:YAG laser. A total of 26 patients with advanced open-angle glaucoma were treated and followed for up to 6 months. In all cases a functioning fistula with a prominent filtering bleb and a marked reduction in the intraocular pressure (from up to 35 mm Hg to < 10 mm Hg) could be achieved primarily. The total energy required was about 4 times lower for erbium:YAG laser was compared with holmium:YAG laser sclerostomies. No complication occurred intraoperatively. Postoperatively, reversible adherence of the iris to the internal ostium was more frequently observed in Ho:YAG laser sclerostomies (60%) and small hyphemas were more often seen in Er:YAG laser sclerostomies (30%). After 6 months of follow-up, about 40% of the fistula remained patent in both groups. In principle, both lasers are suited to serve as energy sources for the described approach. Under the conditions of the present study, different levels of thermal effects did not cause any significant difference in the clinical success rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Reflection measurement during retinal laser coagulation in patients. Development of an automatically controlled dosimeter].

PURPOSE: Retinal laser coagulation has limited reproducibility, because every laser exposition is unpredictably affected by pigmentation and media opacities. This can lead to complications. A feedback-controlled dosimeter would make retinal laser treatment a safer, more reproducible and faster procedure. METHOD: A reflectometer was developed that allows monitoring of the reflection of laser light during standard photocoagulation. Hundreds of coagulations in rabbit eyes and about 12,000 coagulations in patients undergoing routine laser treatment were recorded. RESULTS: The results of the first reflectance measurements in humans are presented along with extensive animal studies. A typical reflectance history was found for different lesion intensities. The degree of retinal whitening correlates with reflectance characteristics. These characteristics allow an early prediction of lesion intensity. Motion during laser exposure affects each coagulation in a fashion similar to spot size and exposure time. CONCLUSION: Reflectometry is the currently most effective means of monitoring lesion development. An automatic dosimeter for retinal photocoagulation seems feasible.

Animals↗

Mechanisms of intraocular photodisruption with picosecond and nanosecond laser pulses.

Nd:YAG laser photodisruption with nanosecond (ns) pulses is an established method for intraocular surgery. In order to assess whether an increased precision can be achieved by the use of picosecond (ps) pulses, the plasma size, the shock wave characteristics, and the cavitation bubble expansion after optical breakdown with ps- and ns-laser pulses were investigated by time-resolved photography and acoustic measurements. Nd:YAG laser pulses with a duration of 30 ps and 6 ns, respectively, were focused into a water-filled glass cuvette. Frequency doubled light from the same laser pulses was optically delayed between 2 ns and 136 ns and used as illumination light source for photography. Since the individual events were well reproducible, the shock wave and bubble wall position could be determined as a function of time. From the slope of these r(t) curves, the shock wave and bubble wall velocities were determined, and the shock wave pressure was calculated from the shock velocity. The plasma size at various laser pulse energies was measured from photographs of the plasma radiation. The breakdown thresholds at 30 ps and 6 ns pulse duration were found to be 15 microJ and 200 microJ, respectively. At threshold, ps-plasmas are shorter than ns-plasmas, but at the same pulse energy they are always approximately 2.5 times longer. The initial shock pressures were 17 kbar after ps-pulses with an energy of 50 microJ, and 21 kbar after 1 mJ ns-pulses. The pressure amplitude decayed much faster after the ps-pulses. The maximum expansion velocity of the cavitation bubble was 350 m/s after a 50 microJ ps-pulse, but 1,600 m/s after a 1 mJ ns-pulse. The side effects of intraocular microsurgery associated with shock wave emission and cavitation bubble expansion can be considerably reduced by the use of ps-pulses, and new applications of photodisruption may become possible.

Eye↗

Intraocular microsurgery with a picosecond Nd:YAG laser.

We investigated the use of picosecond Nd:YAG laser pulses for intraocular microsurgery. With a pulse duration of 100 picoseconds, only 70 microJ of pulse energy is required to consistently produce optical breakdown in the deep vitreous. This pulse energy is nearly two orders of magnitude less than the typical pulse energies used in conventional (nanosecond) photodisruptors. The reduced pulse energy results in a smaller zone of tissue damage, an important consideration when operating close to the retina or other sensitive ocular structures. Efficient cutting action is achieved by applying multiple pulses at a moderately high repetition rate of 50-200 Hz. An in vitro model was developed to assess axial confinement of picosecond photodisruption. In vivo vitreous membrane surgery was performed in experimental rabbit eyes to demonstrate a potential clinical application of picosecond laser-induced optical breakdown.

3T3 Cells↗

Dynamic reflectometer for control of laser photocoagulation on the retina.

In retinal laser photocoagulation, constant exposure parameters do not result in identical lesions. This lack of reproducibility increases the rate of complications from over- or undertreatment and inhibits determination of the optimal treatment endpoints for different retinal disorders. To this end, a feedback-controlled photocoagulator could make retinal photocoagulation a safer, more reproducible, and faster procedure. A dynamic confocal reflectometer was integrated into a slit lamp laser delivery system. Real-time reflectance changes on the retinas of pigmented rabbits were obtained by monitoring the increasing back-scattered light of the coagulating beam during argon laser photocoagulation. Reproducible temporal reflectance patterns were measured that correlated with ophthalmoscopically assessed lesion intensity independent of the exposure parameters, the transparency of the optical media, and the focusing conditions. As a step toward the development of a feedback-controlled photocoagulator, the confocal reflectometer has been proven in animal trials closely resembling clinical practice.

Animals↗

Vascular targeting in photodynamic occlusion of subretinal vessels.

PURPOSE: To evaluate the potential of photodynamic therapy (PDT) using benzoporphyrin derivative (BPD) for occlusion of subretinal neovascular membranes, the authors studied efficiency and collateral damage of PDT-induced photothrombosis in the rabbit choriocapillary layer. METHOD: Benzoporphyrin derivative, a new photosensitizer, currently in clinical trials for tumor therapy, was used. Low-density lipoprotein served as a carrier to enhance selective targeting of vascular endothelial cells. RESULTS: Complete choriocapillary occlusion was achieved at a BPD dose of 2 mg/kg and a radiant exposure as low as 10 J/cm2. When PDT was performed 3 hours after BPD application, damage to the neural retina was minimal. Only inner photoreceptor segments showed mitochondrial swelling probably secondary to choroidal ischemia. Bruch's membrane remained intact. Retinal pigment epithelium was invariably damaged as seen with other photosensitizers. CONCLUSION: Compared with photocoagulation BPD-PDT allows endothelial-bound intraluminal photothrombosis, sparing important structures such as neural retina and Bruch's membrane. It may thus provide a more selective treatment of juxtafoveal and subfoveal neovascular membranes.

Animals↗

Photodynamic therapy of experimental choroidal melanoma using lipoprotein-delivered benzoporphyrin.

BACKGROUND: Benzoporphyrin derivative monoacid (BPD) is a new photosensitizer currently undergoing clinical trial for cutaneous malignancies. Compared with the clinically most frequently used sensitizer, Photofrin, BPD may offer higher tumor phototoxicity, better tissue penetration, and absence of significant skin sensitization. Low-density lipoprotein (LDL) carriers heighten efficiency and selectivity of BPD because neovascular and tumor cells express an increased number of LDL receptors. Hence, in addition to the vaso-occlusive effects similar to most other photosensitizers, LDL-BPD also has been shown to cause direct tumor cell damage. METHODS: Benzoporphyrin derivative monoacid was complexed with human LDL and used in photodynamic treatment of choroidal melanomas experimentally induced in eight albino rabbits. Five rabbits served as controls. Three hours after intravenous injection of 2 mg/kg body weight of LDL-BPD, eight tumors were irradiated at 692 nm and 100 J/cm2 via an argon-pumped dye laser coupled into a slit lamp. RESULTS: Angiography and histologic findings showed immediate photothrombosis after disintegration of endothelial membranes. After complete necrosis of tumor cells within 24 hours, a small fibrotic scar slowly developed. No tumor regrowth was noted up to 6 weeks when animals were killed. CONCLUSION: These data suggest that photodynamic treatment with LDL-BPD may be a promising modality for multiple clinical applications, including tumors and neovascularizations II.

Animals↗

[Experimental studies on the effect of the Er:glass and Cr:Tm:Ho:YAG laser in thermokeratoplasty].

So far the dose-effect ratio of the Holmium laser (wavelength 2.12 microns) and the erbium laser (1.54 microns) for laser thermokeratoplasty (LTK) are not defined in detail. Our study was designed not only to compare the erbium contact and the holmium non-contact applications but also to throw light on the influence of different geometrical application patterns, pulse energies, pulses per coagulation site and repetition rates under experimental conditions. Enucleated sheep and pig eyes were used 2-6 h post mortem, pressurized to 25 mmHg and moisturized with saline solution. Before and after LTK, pachymetry and keratometry were performed. Some specimens were prepared for light and scanning microscopy. The coagulation threshold for the erbium laser in a contact mode with a 200-microns fibre was 25 J/cm2 (ca. 8 mJ/pulse) and for the holmium laser 8 J/cm2 (ca. 2.5 mJ/pulse). The erbium laser was used in a single shot per spot mode, the holmium laser in repeated pulse per spot mode. With the single shot per spot mode, we were able to induce a promising hyperopic shift of up to -3.47 +/- 0.61 D, while myopic changes could only be induced up to +1.89 +/- 0.74 D. Higher changes of up to +8.27 +/- 1.3 D could be achieved by means of repeated pulses per spot (20 pulses, 45 mJ, 10 Hz). Our experiments showed an obvious increase of dioptric changes when using a higher repetition rate while pulse energy and number were kept constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Intrastromal refractive corneal surgery with pico-second Nd:YAG laser pulses].

Intrastromal laser surgery with picosecond pulses aims to achieve refractive changes of the cornea without damaging the epithelium, Bowman's membrane, or the endothelium. For that, a tissue layer with well-defined thickness has to be evaporated by creating laser plasmas within the corneal stroma. We investigated the plasma formation and the plasma-induced shock wave emission and bubble generation (cavitation) in the cornea, as well as the tissue effects and the range for endothelial damage. The laser light source used was an Nd:YAG laser emitting pulses with a duration of 30 ps at a repetition rate of 10 Hz. Intrastromal plasma formation and cavitation were investigated in sheep eyes in vitro by means of time-resolved macro-photography with 20 ns exposure time. Photographs were taken at various delay times (3 microseconds-2 min) after the release of the Nd:YAG laser pulse. The morphology of the laser effects and the incidence of endothelial damage was investigated by light-microscopic inspection of histological cross sections of the irradiated corneas. The minimal plasma size at energies close to the breakdown threshold was about 40 microns. Using a laser effects could be created without causing microscopically detectable damage to the epithelium, endothelium, or Bowman's membrane. To avoid damage, the distance between endothelium and laser focus had to be larger than 150 microns. Shock wave-induced tissue damage was not observed, although the maximum shock wave pressure was up to 13 kbar. The laser-generated intrastromal cavities are at least 10 times larger than the plasma volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Retinal photocoagulation with a pulsed, frequency-doubled Nd:YAG laser (532 nm)].

The small difference in wavelength between an argon laser (514 nm) and a frequency-doubled Nd:YAG laser (532 nm), together with the advantage of the solid-state technology, makes the Nd:YAG laser likely to play a major role in retinal photocoagulation in the near future. For technical reasons all frequency-doubled Nd:YAG lasers work in a quasi-continuous mode, emitting a burst of highly repetitive short laser pulses during the exposure time desired. We investigated the side effects due to high peak irradiances of those short laser pulse trains (Crystal Focus Nd:YAG laser, Emerald; pulse duration 1-10 microseconds, repetition rate 13 KHz) in rabbits in comparison with a standard argon laser system (Zeiss, Visulas, Argon II). The energy necessary for blanching the retina was similar in both cases. As opposed to the argon laser system, subretinal bubbles were regularly visible ophthalmoscopically with the Nd:YAG system, when average powers as high as 200 mW were used. The ED50 power for bubble formation is about 2-3 times above the ED50 power for blanching. Thermal calculations show that this bubble formation effect is likely to be related to the peak power of the short pulses. The hemorrhage threshold is similar in both systems. However, light microscopically there is no difference between the two laser systems. Panretinal photocoagulation (300-500 microns, 100-200 ms) in patients with proliferative diabetic retinopathy produced such bubbles about once per 1000 lesions.

Animals↗

[Selective occlusion of subretinal neovascularization with photodynamic therapy].

Conventional photocoagulation of subretinal membranes induces a non-selective thermal necrosis of retinal and choroidal layers with extensive collateral damage. Hence, this modality is of limited value for the treatment of lesions close to or underneath the fovea. Photodynamic therapy uses systemic administration of a primarily non-toxic photosensitizer with localized light activation of the dye by subthermal light intensities. It provides intraluminal vascular occlusion by means of localized endothelial damage. Enhanced selectivity for neovascularization is achieved by the use of carrier molecules with increased receptor density on proliferating endothelial cells, e.g. low-density lipoproteins (LDL). Benzoporphyrin derivative (BPD), currently in phase I clinical trials, was complexed with LDL. BPD-LDL was used for photodynamic occlusion of the choriocapillary layer in the rabbit model. Subretinal photothrombosis and collateral damage to neural retina, retinal pigment epithelium, Bruch's membrane and large choroidal vessels were documented by ophthalmoscopy, angiography and light and electron microscopic histology. Homogenous vascular occlusion without retinal destruction was induced with light doses as low as 10 J/cm2. Selective neovascular occlusion by photodynamic therapy may allow occlusion of subretinal membranes while preserving retinal integrity and visual function.

Animals↗

[Selective vascular occlusion by repetitive short laser pulse].

The occlusion of arterioles and venules (30 microns in diameter) by means of repeated dye laser pulses (577 nm, 160 microseconds, 0.5 Hz) was studied in the hamster cheek pouch model. Microscopically visible changes during and after irradiation were recorded and monitored by a video system. The energy necessary per pulse for vessel occlusion with a single pulse (arterioles 5 J/cm2, venules 3.5 J/cm2) can be lowered more than 50% with 100 pulses (1.8 J/cm2, 1.2 J/cm2). Rupture of vessels, which regularly occurs with a single pulse, can be totally avoided with 100 repetitive laser pulses. Investigations of the temperature dependence of the occlusion rate of arterioles showed different interaction mechanisms with one pulse and 100 pulses (mechanical and thermal respectively). Light and electron microscopic investigations supported this concept of selective occlusion using repeated short laser pulses. Possible clinical applications are portwine stains of the eyelid, neovascularisation on the cornea and subretinal neovascularisation.

Animals↗

[Photodynamic therapy of experimental, intraocular tumors with benzoporphyrin-lipoprotein].

Photodynamic therapy (PDT) with its potential for precise localization and absence of severe side effects such as radiation retinopathy may be particularly appropriate for the treatment of intraocular tumors. Benzoporphyrin (BPD), a potent photosensitizer currently in clinical trial, absorbs light at 692 nm, thus allowing sufficient tissue penetration due to minor light absorption in melanin and hemoglobin. The efficiency and selectivity of BPD are significantly pronounced through preassociation with low-density lipoprotein (LDL), since proliferating cells exhibit an increased metabolism of lipoproteins. As an experimental model Greene's melanomas were implanted either into the iris or choroid of albino rabbits. Irradiation at a radiation energy of 80 for iris and 100 J/cm2 for choroidal tumors 3 h after the i.v. injection of BPD-LDL (2 mg/kg) was administered via a laser arrangement with argon-pumped dye-laser, using the slit-lamp. Angiographies and LM/EM histologies were done immediately, and 1, 3, and 14-21 days post-exposure. All 16 treated tumors demonstrated complete regression with a remaining avascular, fibrotic scar. Immediate vascular occlusion within the tumor was seen angiographically, suggesting a direct vascular mechanism. Histologically, two primary mechanisms could be detected: destruction of neovascular endothelial cells and intracellular tumor cell damage. These results indicate that PDT using BPD-LDL complexes may provide an efficient and selective modality for the management of intraocular neoplasms. The availability of new and potent photosensitizers may also lead to broader clinical applications.

Animals↗

Laser sclerostomy ab externo using the erbium: YAG laser. First results of a clinical study.

A new approach to fistulating glaucoma surgery, laser sclerostomy ab externo, was investigated in a clinical study. A pulsed (200 microseconds) erbium-YAG laser was used, as its wavelength (2940 nm) is very well absorbed by tissue water. The laser energy was transmitted via a fiber to an application probe with a cannula particularly designed to guide another fiber into the subconjunctival space. Nine patients with advanced open-angle or neovascular glaucoma were treated. In all cases a functioning fistula with a prominent filtering bleb and a reduction of the intraocular pressure (from up to 50 mmHg to 8-18 mmHg) could be achieved. The total energy was 60 mJ on average. No complication occurred intraoperatively. Postoperatively, all fistulas in patients with neovascular glaucoma (n = 6) were impatent after approx. 7 days due to iris adherence to the internal ostium and episcleral scarring. In cases of open-angle glaucoma (n = 3) a patent fistula persisted for several months. Variation of the exposure parameters, the use of antiproliferative drugs, and a less restrictive selection of patients could further improve the success rate.

Fiber Optic Technology↗

Intraocular photodisruption with picosecond and nanosecond laser pulses: tissue effects in cornea, lens, and retina.

PURPOSE: Nd:YAG laser photodisruption with nanosecond (ns) pulses in the millijoule range is an established tool for intraocular surgery. This study investigates tissue effects in cornea, lens, and retina to assess whether picosecond (ps) pulses with energies in the microjoule range can increase the surgical precision, reduce collateral damage, and allow applications requiring more localized tissue effects than can be achieved with ns pulses. METHODS: Both ps and ns Nd:YAG laser effects on Descemet's membrane, in the corneal stroma, in the lens, and at the retina were investigated in vitro in bovine and sheep eyes and in cataractous human lens nuclei. For each tissue, the optical breakdown threshold was determined. The morphology of the tissue effects and the damage range of the laser pulses were examined by light and scanning electron microscopy. The cavitation bubble dynamics during the formation of corneal intrastromal laser effects were documented by time-resolved photography. RESULTS: The optical breakdown threshold for ps pulses in clear cornea, lens, and vitreous is, on average, 12 times lower than that for ns pulses. In cataractous lens nuclei, it is lower by a factor of 7. Using ps pulses, Descemet's membrane could be dissected with fewer disruptive side effects than with ns pulses, whereby the damage range decreased by a factor of 3. The range for retinal damage was only 0.5 mm when 200 microJ ps pulses were focused into the vitreous. Picosecond pulses could be used for corneal intrastromal tissue evaporation without damaging the corneal epithelium or endothelium, when the pulses were applied in the anterior part of the stroma. The range for endothelial damage was 150 microns at 80 microJ pulse energy. Intrastromal corneal refractive surgery is compromised by the laser-induced cavitation effects. Tissue displacement during bubble expansion is more pronounced than tissue evaporation, and irregular bubble formation creates difficulties in producing predictable refractive changes. CONCLUSIONS: The use of ps pulses improves the precision of intraocular Nd:YAG laser surgery and diminishes unwanted disruptive side effects, thereby widening the field of potential applications. Promising fields for further studies are intrastromal corneal refractive surgery, cataract fragmentation, membrane cutting, and vitreolysis close to the retina.

Animals↗

Microphotocoagulation: selective effects of repetitive short laser pulses.

Repetitive exposure to short laser pulses is shown to cause selective damage to absorbing structures (cells, organelles, or enzymes) with pulse energies below the threshold energy for single-pulse damage. Directly adjacent structures are spared in vivo. Additivity of (presumably nonphotochemical) subthreshold effects is demonstrated. Selective damage to the retinal pigment epithelium with sparing of the neural retina is shown (514 nm, 5 microseconds, 1-500 pulses at 500 Hz, 2- to 10-microJ pulse energy). A melanin granule model has been developed and applied to the experimental situation. Histological results as well as the basic mechanism for these effects are discussed.

Animals↗