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R Brinkmann

Publications and source records attributed to R Brinkmann.

At least 19 recordsLinked to original sources

Variability of RPE reaction in two cases after selective RPE laser effects in prophylactic treatment of drusen.

BACKGROUND: The value of prophylactic photocoagulation of soft drusen is unclear. Photocoagulation is usually performed by a continuous wave laser. METHODS: We report the cases of two patients with age-related macular degeneration with soft drusen who were treated by selective retinal pigment epithelium (RPE) photocoagulation of a pulsed Nd:YLF (527 nm) laser. Laser parameters were: wavelength 527 nm, number of pulses in a train 500, pulse duration 1.7 microseconds, energy per pulse 70 microJ, spot size 160 microns, repetition rate 500 Hz. RESULTS: Dosimetry performed individually showed that in both patients laser photocoagulation was performed at the threshold of RPE disruption. None of the laser effects was visible during photocoagulation. They were detectable only by fluorescein angiography. Despite identical photocoagulation parameters the RPE reaction was completely different. In the first patient RPE hyperpigmentation was notable at most photocoagulation sites and the drusen had disappeared after 6 months. In the second patient the laser effects were not visible after 6 months by biomicroscopy and the drusen stayed unchanged. CONCLUSION: These findings could reflect different repair mechanisms of the RPE after alteration and could represent a sign of a different viable stage in the life of RPE cells. Close attention should be paid to this phenomenon in the various drusen studies currently under way.

Fluorescein Angiography

Continuous-wave diode laser thermokeratoplasty: first clinical experience in blind human eyes.

PURPOSE: To evaluate the safety and stability of laser thermokeratoplasty (LTK) with a continuous-wave diode laser in blind human eyes and to optimize parameters for a study in sighted eyes. SETTING: Department of Ophthalmology, Medical University Lübeck, Germany. METHODS: A continuous-wave diode laser was set to emit radiation with a wavelength of 1.854 microns (Group 1, n = 4) or 1.870 microns (Group 2, n = 4) and 100 to 150 mW power for 10 seconds. A focusing handpiece was coupled with an application mask and fixed by partial vacuum to the conjunctiva or cornea. The radiation was focused into the corneal stroma between 400 and 600 microns in Group 1 and set to 1000 microns in Group 2. Eight (Group 1, single ring) or 16 (Group 2, double ring) coagulations were applied. RESULTS: The refractive change increased with higher laser power and smaller ring diameters. Two rings of coagulations provided higher and more stable refractive changes of up to 5.66 diopters (D) than a single ring. The refractive effect stabilized between 3 and 6 months postoperatively. At 1 year, mean refractive change was +0.99 D +/- 0.39 (SD) in Group 1 and +2.32 +/- 2.24 D in Group 2. Extensive endothelial damage occurred in Group 1 but was minimal in Group 2. CONCLUSIONS: Diode LTK was used to treat hyperopia safely and effectively. Regression occurred mainly in the first 3 postoperative months. With a wavelength of 1.870 microns, corneal endothelial damage was limited.

Adult

Diode laser thermokeratoplasty: application strategy and dosimetry.

PURPOSE: To investigate suitable application parameters for efficient hyperopic correction by laser thermokeratoplasty (LTK) using mid-infrared laser diodes. SETTING: Medical Laser Center Lübeck, Lübeck, Germany. METHOD: A tunable continuous-wave laser diode in the spectral range between 1.845 and 1.871 microns was used. Transmitted by waveguides, the laser energy was used to induce coagulations on freshly enucleated porcine eyes to increase corneal curvature. The coagulations were equidistantly applied by a fiber-cornea contact and a noncontact focusing device that were adjusted on a ring concentric to the corneal apex. Different laser parameters and application geometries were evaluated. Refractive changes were measured by computer-assisted corneal topography before and after treatment. Polarization light microscopy and temperature calculations were used to analyze the coagulations. RESULTS: Because of the tunability of the laser diode, the influence of the corneal absorption coefficient (between 0.9 and 1.6 mm-1) on the refractive change could be measured. A laser power between 125 and 200 mW was adequate to achieve refractive changes up to 10.0 diopters. In the preferable focusing device, the refractive change increased almost logarithmically with the irradiation time up to 15 seconds. The number of coagulations on a fixed application ring showed no significant influence on refractive change; however, it showed an almost linear decrease with increasing ring diameter from 5.0 to 10.0 mm. Histological analysis revealed 3 stages of thermal damage. CONCLUSION: Diode LTK provided defined and uniform coagulations when using a well-adapted focusing device, resulting in sufficient refractive change. The results indicate that diode LTK is superior to pulsed holmium LTK.

Absorption

[Optical coherence tomography of the cornea and the anterior eye segment].

TARGET: The method of optical coherence tomography (OCT) was investigated regarding its suitability and limits for measuring the cornea and the anterior segment of the eye. Furthermore, the stromal expansion of thermally induced lesions in the cornea directly after irradiation was determined within the scope of the laser thermokeratoplasty (LTK). MATERIAL AND METHODS: With the experimental scanning OCT system, x-z sections of the anterior eye segment were made with an optical resolution of about 20 microns axially and 25 microns laterally. Freshly enucleated, tonicized porcine eyes were used as model eyes. Thermal lesions were applied with a continuously emitting laser diode (lambda = 1.86 microns) and various radiation parameters. Before and after coagulation, the cornea was viewed from limbus to limbus in a central OCT scan and the individual coagulation source was measured. RESULTS: Global and local changes of the thickness of the cornea as well as the distance between cornea and lens were measured with high precision. Thermal lesions in their expansion can be dearly presented and matching well with the histologically stained sections, but are not as exactly defined at the edges due to the limited optical resolution, as known from histological preparations. CONCLUSION: With the OCT method quantitative measuring of the anterior eye segment can be performed in vitro and with reduced resolutions also in vivo. Due to the qualitatively good correspondence regarding the dimensions of thermal damage of the cornea with histologically obtained morphometric results, this method can be used for supervision of coagulation directly after LTK as well as for examination of the individual healing process.

Animals

[Imaging of laser thermokeratoplasty lesions by optical low coherence tomography and polarization microscopy after Sirius Red staining].

BACKGROUND: Information on the extent and degree of the thermal effect produced is of great importance for control of the laser dosage in laser thermokeratoplasty (LTK) and for postoperative follow-up. We investigated on acute LTK effects which information images obtained by optical low coherence tomography (OCT) offer compared to those obtained by polarization microscopy. METHODS: Porcine eyes were irradiated through a 400 microns quartz fiber using light from a laser diode emitting up to 300 mW at a wavelength of 1.86 microns. Thermal lesions of varying strength were scanned using an experimental OCT device with about 25 microns lateral and 20 microns axial resolution. Histologic evaluation of the scanned areas was done by polarization microscopy after Sirlus-Red staining, and similar lesions were also analyzed by TEM. RESULTS: Both methods differentiated three damage zones a transition zone, a zone of moderate coagulation, and a central zone of strong coagulation. In the transition zone, increased birefringence was seen in polarization microscopy, which correlated with increased light scattering seen in the OCT images. In the moderately coagulated zone, a decrease in birefringence was associated with an even stronger increase of the OCT signal. In the central zone, a loss of the fibrillar tissue structure was observed, which led to a complete loss of birefringence and a strong reduction of the OCT signal. CONCLUSIONS: Although OCT does not provide the detailed information on thermal changes of tissue seen by the histologic method, it offers information on the extent and degree of tissue changes without preparation artifacts and provides a non-invasive method of immediate and follow-up control of LTK lesions. A quantitative analysis of changes in corneal thickness and curvature is much simpler than by a slit lamp. Time-resolved measurements of corneal light scattering may be used for on-line control of the laser-light dosage during LTK.

Animals

Histologic analysis of thermal effects of laser thermokeratoplasty and corneal ablation using Sirius-red polarization microscopy.

PURPOSE: To evaluate how well several histologic techniques differentiate degrees of thermally induced changes in corneal tissue after laser thermokeratoplasty (LTK) or corneal ablation. SETTING: Medical Laser Center Lübeck, Germany. METHODS: Corneas of freshly enucleated porcine eyes were treated with a continuous wave laser diode (1.86 microns) and a pulsed chromium-thulium-holmium: YAG laser (2.1 microns) to produce LTK lesions or ablated with a Q-switched and a free-running chromium-erbium: YSGG laser (2.70 microns), a free-running erbium: YAG laser (2.94 microns), and an argon-fluoride excimer laser (193 nm). The lesions were evaluated by light microscopy (LM) (hematoxylin and eosin, Azan, van Gieson's, and Masson-Goldner's trichrome stains), transmission electron microscopy (TEM), and polarization microscopy after Sirius-red staining. Sirius-red, a strongly elongated, birefringent molecule binding parallel to collagen molecules, was used to enhance corneal birefringence. RESULTS: With routine LM, it was difficult to discriminate the degrees of thermal alterations in LTK lesions. Combined Sirius-red staining and polarization microscopy distinguished between a strongly coagulated central zone and the transition zone to normal tissue. Sirius-red uptake was increased in both zones, reflecting the availability of new binding sites. The central zone appeared darker under polarization than normal collagen because of a loss of birefringence. Intrinsic birefringence was greatly reduced; however, form birefringence partly remained as long as some collagen fibrils were intact. In the center of very strong lesions, where the collagen was hyalinized, birefringence was completely lost because of the complete disintegration of the fibrillar structure, which was visible under TEM. The transition zone toward normal cornea showed increased birefringence because the natural birefringence was largely preserved and enhanced by the increased Sirius-red uptake. Mechanical stretching between neighboring LTK lesions was manifested by increased birefringence. CONCLUSION: Sirius red offered an improved and simple histologic method for analyzing thermal collagen changes. It may contribute to a better understanding of the working mechanisms of LTK and improve analysis of thermal effects in corneal ablation.

Animals

Ablation dynamics in laser sclerostomy Ab externo by means of pulsed lasers in the mid-infrared spectral range.

BACKGROUND AND OBJECTIVE: Sclerostomy ab externo with pulsed laser systems is currently in phase II clinical trials. The authors investigated the ablation dynamics of tissue treated with pulsed laser systems in the mid-infrared range to estimate the extent of thermo-mechanical damage to the sclera and the anterior chamber. MATERIALS AND METHODS: Freshly harvested porcine eyes were used. A bare 400-micron fiber in direct contact with tissue was used for fistulization. Polarization light microscopy, fast-flash photography, as well as optical and acoustic transients were performed for analysis. RESULTS: Substantial mechanical tissue deformation and dissections were found during pulsed laser ablation. The mechanical damage range within tissue far exceeds the pure thermal damage zone. Aspheric cavitation bubbles of up to 3 mm in length penetrate the anterior chamber after perforation. The cavitation demonstrates a significantly larger time constant in tissue than in water. CONCLUSIONS: Early fistula occlusions due to iris adherences may be attributed to iris trauma caused by cavitation. In response to the findings of this study, the authors propose an automatic feedback system to control the ablation process and minimize secondary ocular tissue effects. With respect to the overall damage zones, a new continuous-wave, mid-infrared diode laser system seems to be superior to pulsed laser systems.

Animals

The effect of simian immunodeficiency virus infection in vitro and in vivo on the cytokine production of isolated microglia and peripheral macrophages from rhesus monkey.

Microglia are the major target for human immunodeficiency virus (HIV) infection within the central nervous system. Because only a few cells are productively infected, it has been suggested that an aberrant cytokine production by this cell population may be an indirect mechanism leading to the development of neurological disorders in HIV-infected patients. Therefore we decided to study the secretion pattern of several interleukins (IL) by microglial cells and peripheral blood macrophages isolated from uninfected and simian immunodeficiency virus (SIV)-infected Rhesus monkeys. We found that uninfected, unstimulated primate microglia produce more IL-6 and less TNF alpha than peripheral blood macrophages, but generate comparable levels of IL-1 beta and IL-8. After infection with SIV in vitro, synthesis of all cytokines tested is increased compared to uninfected cultures and to peripheral blood macrophages. Microglia isolated from infected animals produce more IL-8 and TNF alpha than the uninfected cultures and display a strongly increased capacity to secrete TNF alpha upon stimulation with lipopolysaccharide. In addition, production of IL-6 by in vivo-infected microglia increases with time in culture to very high levels despite the fact that only a few cells contained replicating virus. These findings clearly show that the cytokine production of microglia is impaired after SIV infection both in vitro and in vivo and that a low level of viral replication is sufficient for these alterations to occur. In conclusion, the results of this study further support a possible role of cytokines in the pathogenesis of neuro-AIDS.

Animals

Morphological and biomorphometrical observations on laser thermal keratoplasty. Histological and biomorphometrical examination of the relationship between refractive change and the volume following Cr:Tm:Ho:YAG laser treatment.

Laser thermal keratoplasty (LTK) is currently under clinical trial for the correction of hyperopia and hyperopic astigmatism by means of collagen coagulation in the peripheral cornea. The purpose of our study was to optimize the ratio between the volume of damaged corneal stroma and the refractive effect so as to minimize potential side effects such as endothelial damage or induction of glare phenomena. We therefore performed histological and morphometrical examinations of enucleated pig eyes to determine the relationship between the coagulated stromal volume and the refractive change after LTK using a pulsed Cr:Tm:Ho:YAG laser (wavelength 2.12 microns) on enucleated pig eyes. The refractive change was documented with a Littman ophthalmometer. Morphometrical analysis was performed using polarized light microscopy of sirius red-stained specimens. This special stain separated the thermally changed stroma into a dark nonbirefringent center and a birefringent peripheral zone. The volume of both zones was positively correlated with the refractive change induced. The volume was in turn influenced by the choice of laser parameters. From the ratio of the volume to the refractive change it was found that pulse energies above 30 mJ let to an enlargement of the coagulation volume without increasing the refractive change effectively. The use of high pulse energies did not improve the effect of LTK but only increased the risk of unwanted side effects. However, an increase in the laser repetition rate at a constant pulse number per spot led to refractive changes with minimal coagulation volume. The highest relative refractive change was achieved with a dark central zone and a birefringent zone, each having a volume of about 50-80 x 10(-3) mm3.

Animals

[Use of the confocal laser scanning method for determining corneal topography and corneal tissue effects in refractive corneal surgery].

Refraction of the cornea head been generally measured with ophthalmometers or computer disk keratometers. We therefore used a confocal laser scanning system for measurement of the corneal topography. Enucleated tonicized pig eyes were measured before and after laser thermokeratoplasty (LTK). The topographical data were used to determine refraction and refractive change; the data were stored digitally. The single images and their differences were displayed on a PC. Unlike conventional ophthalmometry, confocal laser scanning can demonstrate the topographical shape, showing the overall topography of the cornea and local corneal effects, e.g., coagulation, mechanical lesions or high-energy laser effects. Topographical laser scanning has proven to be a generally useful method of determining refraction and surface alterations in corneal refractive surgery.

Animals

Photofragmentation of lens nuclei using the Er: YAG laser: preliminary report of an in vitro study.

The energy of the erbium: YAG laser (2.940-nm wave-length) can be used for minimally traumatic photoablation due to its high absorption at the tissue water and its consequently low penetration depth. Laser sclerostomy ab externo, an application of this principle, has undergone advanced clinical investigation. Another potential application is photofragmentation of the lens for cataract extraction. A laboratory model Er: YAG laser (flashlamp-pumped. 200-microseconds pulse length, 5-Hz repetition frequency) was coupled to a short low-OH quartz fiber (400 microns in diameter). The laser energy was applied by direct contact of the fiber tip to human lenses with very dense cataract. The lenses rested in a small cuvette filled with an aqueous-humor-analogous fluid. The fragmentablation rate was evaluated in relation to the number of pulses and the pulse energy. A laser-triggered flash-photography unit was engaged to visualize the ablation dynamics. We found tissue-ablation rates to range from 4 to 19 micrograms/pulse, depending on the nucleus density and ulse energy. The maximal size of the removed fragments was always below 500 microns. During ablation, rapidly increasing and collapsing cavitation bubbles were photographed at the distal tip of the application fiber. The impact radius of these cavitation effects markedly exceeded the pure penetration depth of laser radiation at a 2.9-microns wavelength. A clinical application of the method should be possible as judged by the results obtained for tissue-ablation rate and fragment size. Cavitation-bubble dynamics seems to be responsible for the high fragmentation efficiency. Special application probes have to be developed to optimize ablation and to prevent inadvertent destruction of the posterior lens capsule by cavitation effects.

Humans

Sequelae of definitive radiation therapy for prostate cancer localized to the pelvis.

OBJECTIVES: To evaluate sequelae and estimate quality of life utilizing a survey instrument in 133 consecutive patients who have undergone definitive radiation therapy for localized prostate cancer. METHODS: All patients reported on have been followed for 14 to 60 months (median, 31 months) after radiation therapy and only patients with definitive prostate radiation therapy are included. Of the patients still alive at time of follow-up, 115 were mailed the questionnaire. Data regarding tumor grade and stage as well as treatment were extracted from patient files. RESULTS: Of the 91% of patients who returned the questionnaire, 11% used a pad and 13% leaked more than a few drops of urine daily. Of all the respondents, 9% stated that incontinence was a problem, and 31% found urinary leaking significantly worsened after radiation therapy compared with before their diagnosis of prostate cancer. With respect to sexual function, 77% recalled being able to have full or partial erections prior to radiation therapy. At some time after radiation therapy, 22% of previously potent respondents were able to have a full erection and 41% were able to have a partial erection. Twenty-nine percent of all patients who were able to establish an erection prior to radiation therapy reported that impotence was a problem at the time of follow-up. Forty-nine percent of patients had abdominal pain, diarrhea, or abdominal cramping during or after radiation therapy and 31% of all patients still had some intestinal symptoms at the time of follow-up. Eighteen percent of all patients were significantly bothered by one or more of these bowel problems. Overall, 31% of all patients reported a persistent degree of physical discomfort that they believed was secondary to their prostate cancer or the effect of treatment. Eighty-one percent were satisfied with radiation therapy and 97% of the patients said they would have radiation therapy again if faced with the decision. CONCLUSIONS: Utilizing a sensitive questionnaire on patients who had definitive radiation therapy for prostate cancer, we found the incidence of patients bothered by incontinence to be surprisingly frequent and higher than previously reported. The frequency of impotence is similar to previous studies. However, when our incontinence and impotence data were compared to Medicare patients who had undergone radical prostatectomy, the frequencies after radiation therapy were significantly lower. Despite the rates of sequelae, the patients were generally satisfied with the decision to undergo radiation therapy and with the medical treatment received.

Aged

Benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common cause of bladder outlet obstruction and voiding symptoms in elderly men. The pathogenesis is not fully determined but a combination of androgens and age are needed for development of BPH. Symptoms of BPH are divided into obstructive and irritative symptoms but large interpersonal variability is found and no specific BPH symptom exists. Treatment modalities include surgery (TURP, TUIP, open prostatectomy, laser ablation, balloon dilatation, hyperthermia and thermotherapy, and urethral stents) and medical therapy. TURP is the gold standard treatment and TUIP is a safe and effective alternative to TURP in patients with smaller prostates. Laser ablation, hyperthermia and thermotherapy, and urethral stents are at the present time under investigation. Balloon dilatation is FDA-approved but not often used because of low efficacy and poor long-term results. Medical treatment includes alpha-blocker or finasteride treatment and is indicated in patients with moderate to severe symptoms of BPH without a strong indication for surgery.

Humans

[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

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

In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus.

The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIDS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIVmac251 strain as well as the infectious clone (SIV239). Infectious virus was produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue.

Animals

Human immunodeficiency virus infection in microglia: correlation between cells infected in the brain and cells cultured from infectious brain tissue.

In acquired immunodeficiency syndrome, the lesions of the central nervous system in association with the human immunodeficiency virus are thought to be related to an infection of microglia, although no studies are available in which cultured and physiological characteristics of microglia cells infected in vivo have been examined. In this report, we used brain tissue from a child dying of human immunodeficiency virus infection and show that microglia cells were the main cell population being infected. Moreover, isolated macrophage-like cells from fresh brain material revealed a close resemblance to peripheral blood macrophages in their content of surface and intracellular antigens. No virus particles or viral antigens were produced by these cells during the first week of cultivation. Productive infection was readily apparent, however, by day 30. This finding illustrates the slow nature of the virus life cycle in these cells and the minimal cytopathology that accompanied the infection.

Brain