Automatische Photokoagulation an der Netzhaut des Auges (AutoPhoN)

Die Photokoagulation der Retina gilt als die erfolgreichste therapeutische Anwendung des Lasers in der gesamten Medizin. Sie wird seit Anfang der 70er Jahre nahe­zu un­ver­ändert durchgeführt und ist als Standardtherapie für verschiedenste Netzhauterkran­kungen am Augen­hinter­grund etabliert. Jedes Jahr werden allein in Deutschland ca. 1 Milli­on Behand­lungen durchgeführt.

Die während der Bestrahlung erzielte Temperaturerhöhung definiert das Schädigungs­volu­men. Sie wird neben der Laserleistung durch die Lichtstreuung im Auge und die lokale Absorption des Fundus bestimmt, die selbst innerhalb eines Auges stark variieren. Die Leistung des Lasers wird bisher vom Operateur so dosiert, dass gräuliche Läsio­nen der Netzhaut im Weißlicht sichtbar werden, als Folge der ein­set­zenden Lichtstreuung durch Koagulation. Die resul­tierende Aus­dehnung des irreparablen Netzhautschadens ist meist viel zu groß und sehr ungleich, da die Laser­leistung nicht für jede Koagulation angepasst werden kann (Abb. 1).

Wir haben eine optoakustische Methode entwickelt, mit der es erstmals möglich ist, die Temperaturerhöhung während der Photokoagulation der Netzhaut in Echtzeit zu messen. Hierbei macht man sich die Temperaturabhängigkeit des thermischen Expansionskoeffizienten des Gewebes zu Nutze (Abb. 2). Ziel des Projektes ist es, eine automatische Dosimetrie der Laserbe­strahlung zu realisieren, die immer eine reproduzierbar gleiche, frei wähl­bare minimal invasive Koagulationsstärke erzielt (Abb. 1). Hier­zu soll die Leistung des Behand­lungs­­lasers auf einen zu ermittelnden Solltem­pe­ra­tur­verlauf ge­regelt wer­den. Ist diese Soll­­temperatur erreicht, wird der Be­hand­lungs­la­ser z.B. auto­ma­tisch abgeschaltet.

Eine solche auto­ma­­tisierte Dosierung wäre vor­teilhaft für den ge­sam­ten Ablauf der Be­hand­lung, den Patienten, den ausführenden Arzt so­wie auch sozioökonomisch:

  • Sichere, verkürzte Behandlung, reproduzierbar minimal invasive Koagulationen
  • Reduzierung der Sehverluste und keine Schmerzen bei Behandlung für den Patienten
  • Geringere Zahl der Behandlungen bei Diabetes
  • Frühbehandlung von Drusen zur Prävention der Altersbedingten Makuladegeneration (AMD)

Abb. 3 zeigt bereits gemessene Temperaturverläufe am Patienten. Abb. 4 zeigt erste in-vitro Ergebnisse einer OCT-basierten Messung von Phasenänderungen während der Netzhautkoagulation, die in Temperaturänderungen umgerechnet werden können.

Aktuelle Arbeiten

  • Optimierung der Bestrahlung und der Druckdetektion
  • OCT zur Echtzeit-Temperaturmessung
  • Realisierung der Temperaturregelung
  • Klinische Studien

Das Projekt wird vom BMBF gefördert und wurde mit dem Innovationspreis zur Förderung der Medizintechnik ausgezeichnet. Partner des Projekts sind das Medizinische Laserzentrum Lübeck, die Augenklinik des UK S-H, Campus Kiel sowie die Firma Carl Zeiss Meditec AG, Jena.

Publikationen zur automatischen Photokoagulation

2012

  • Koinzer, Stefan and Schlott, Kerstin and Portz, Lea and Ptaszynski, Lars and Baade, Alexander and Bever, Marco and Saeger, Mark and Caliebe, Amke and Denner, Renè and Birngruber, Reginald and Brinkmann, Ralf and Roider, Johann: Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation. Journal of Biophotonics, pp. n/a-n/a, 2012
    BibTeX
    @article{Koinzer,
       author = {Koinzer, Stefan and Schlott, Kerstin and Portz, Lea and Ptaszynski, Lars and Baade, Alexander and Bever, Marco and Saeger, Mark and Caliebe, Amke and Denner, Renè and Birngruber, Reginald and Brinkmann, Ralf and Roider, Johann},
       title = {Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation},
       journal = {Journal of Biophotonics},
       pages = {n/a-n/a},
       abstract = {We conducted a study to correlate the retinal temperature rise during photocoagulation to the afterward detected tissue effect in optical coherence tomography (OCT). 504 photocoagulation lesions were examined in 20 patients. The retinal temperature increase was determined in real-time during treatment based on thermoelastic tissue expansion which was probed by repetitively applied ns laser pulses. The tissue effect was examined on fundus images and OCT images of individualized lesions. We discerned seven characteristic morphological OCT lesion classes. Their validity was confirmed by increasing visibility and diameters. Mean peak temperatures at the end of irradiation ranged from approx. 60 °C to beyond 100 °C, depending on burn intensity. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)},
       keywords = {laser photocoagulation
    optoacoustics
    photocoagulation
    retinal temperature
    spectral domain optical coherence tomography
    OCT
    subthreshold
    classification},
       year = {2012}
    }
  • Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Bever, Marco and Baade, Alex and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf: Automatic temperature controlled retinal photocoagulation. Journal of Biomedical Optics, no. 17, pp. 061223, 2012
    BibTeX Link
    @article{Schlott2012,
       author = {Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Bever, Marco and Baade, Alex and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Automatic temperature controlled retinal photocoagulation},
       journal = {Journal of Biomedical Optics},
       volume = {17},
       number = {6},
       pages = {061223},
       keywords = {AutoPhoN},
       year = {2012}
    }
    

1986

  • Gabel, V. P. and Birngruber, R. and Lorenz, B.: Clinical relevance of a dosage device for laser photocoagulation. Klin Monbl Augenheilkd, no. 188, pp. 263-5, 1986
    BibTeX Link Link
    @article{Gabel1986,
       author = {Gabel, V. P. and Birngruber, R. and Lorenz, B.},
       title = {Clinical relevance of a dosage device for laser photocoagulation},
       journal = {Klin Monbl Augenheilkd},
       volume = {188},
       number = {4},
       pages = {263-5},
       note = {Gabel, V P
    Birngruber, R
    Lorenz, B
    GERMANY, WEST
    Klin Monbl Augenheilkd. 1986 Apr;188(4):263-5.},
       abstract = {Fundus reflectometry constitutes a procedure with which dosage can be precisely regulated during the coagulation process. During retinal coagulation, for example, it is possible with this method to administer coagulations of uniform intensity regardless of variations in either the quality of the fundus image or the absorption of the pigmented structures. This can be useful for coagulation procedures which have to be confined for the most part to the pigment epithelium, as for example in the treatment of central serous retinopathy or in panretinal photocoagulation, where the functional therapeutic principle is still not clearly understood. Another area of application for reflectometric laser coagulation will be laser trabeculoplasty, in which barely detectable lesions have to be placed in the trabecular meshwork.},
       keywords = {*Computers
    Diabetic Retinopathy/surgery
    Humans
    *Laser Therapy
    Pigment Epithelium of Eye/surgery
    Retinal Detachment/surgery
    Retinal Diseases/*surgery
    Retinal Vein/surgery
    Trabecular Meshwork/surgery
    AutoPhoN},
       ISSN = {0023-2165 (Print)
    0023-2165 (Linking)},
       DOI = {10.1055/s-2008-1050625},
       url = {http://www.ncbi.nlm.nih.gov/pubmed/3723965},
       year = {1986},
       type = {Journal Article}
    }
    

1983

  • Birngruber, Reginald and Gabel, V. P. and Hillenkamp, F.: Experimental studies of laser thermal retinal injury. Health Phys, no. 44, pp. 519-31, 1983
    BibTeX Link
    @article{Birngruber1983,
       author = {Birngruber, Reginald and Gabel, V. P. and Hillenkamp, F.},
       title = {Experimental studies of laser thermal retinal injury},
       journal = {Health Phys},
       volume = {44},
       number = {5},
       pages = {519-31},
       note = {0017-9078 (Print)
    Journal Article},
       abstract = {In damage tests conducted on rabbit and monkey eyes, the threshold values for retinal damage resulting from different laser radiation were determined. The reproduction of the "worst-case" situation was ensured by the test apparatus. All physical parameters, such as power/energy, exposure time, and retinal spot, were carefully controlled. Probit analysis showed a very precise determination of the threshold values based on ophthalmoscopical visibility. The attempt of a simple physical interpretation of the thresholds leads to contradictions in major points, so a detailed calculation of damage functions and thermal model calculations are necessary.},
       keywords = {Animals
    Lasers/*adverse effects
    Macaca
    Rabbits
    Retina/*injuries
    AutoPhoN},
       url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6853172},
       year = {1983},
       type = {Journal Article}
    }
    

1977

  • Birngruber, R. and Gabel, V. P. and Hillenkamp, F.: Fundus reflectometry: a step towards optimization of the retina photocoagulation. Mod Probl Ophthalmol, no. 18, pp. 383-90, 1977
    BibTeX Link
    @article{BGB1977,
       author = {Birngruber, R. and Gabel, V. P. and Hillenkamp, F.},
       title = {Fundus reflectometry: a step towards optimization of the retina photocoagulation},
       journal = {Mod Probl Ophthalmol},
       volume = {18},
       pages = {383-90},
       note = {Birngruber, R
    Gabel, V P
    Hillenkamp, F
    SWITZERLAND
    Mod Probl Ophthalmol. 1977;18:383-90.},
       abstract = {A method is described for monitoring the light reflected from exposed areas during and after argon laser photocoagulation of rabbit eyes. The light serves as a measure of the retinal blanching and thus of the tissue reaction. It is shown, that the reflected light changes its time-dependent behavior qualitatively if hemorrhages occur. The energy necessary for a therapeutic coagulation is shown to decrease with decreasing exposure time as does the therapeutic band width for clinical coagulations. A relationship between exposure time and therapeutic band width was found and is discussed.},
       keywords = {Animals
    *Fundus Oculi
    *Laser Therapy
    Lasers/adverse effects/*methods
    Photometry/*methods
    Rabbits
    Retina/*surgery
    Retinal Hemorrhage/etiology
    AutoPhoN},
       year = {1977}
    }
    

  • Schlott, Kerstin and Langejürgen, Jens and Bever, Marco and Koinzer, Stefan and Birngruber, Reginald and Brinkmann, Ralf: Time resolved detection of tissue denaturation during retinal photocoagulation. pp. 73730E-73730E,
    BibTeX Link
    @inproceedings{Schlott2009,
       author = {Schlott, Kerstin and Langejürgen, Jens and Bever, Marco and Koinzer, Stefan and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Time resolved detection of tissue denaturation during retinal photocoagulation},
       editor = {7373, Proc. SPIE},
       pages = {73730E-73730E},
       note = {10.1117/12.831877},
       abstract = {The retinal photocoagulation is an established treatment method for different retinal diseases. The extent of the thermal coagulations depends strongly on the generated temperature increase. Until now the dosage is based on a pool of experience of the treating physicians as well as the appearance of the whitish lesions on the retina. The temperature course during photocoagulation can be measured in real-time by optoacoustics. A frequency-doubled Q-switched Nd:YLF laser (523nm, 75 ns) is used for optoacoustic excitation and a continuous-wave Nd:YAG laser (532nm) with adjustable irradiation time and power for heating of the fundus tissue. The onset of coagulation is determined by a photodiode that is placed directly behind enucleated porcine eyes, which served as a model. The onset of coagulation is observed clearly when scattering sets in. The required power for coagulation increases exponentially with decreasing irradiation time. The first results on rabbit eyes in vivo indicate that the onset of coagulation defined by just barely visibile lesions at a slit lamp sets in at an ED50 threshold temperature of 63°C for an irradiation time of 400 ms. In conclusion, optoacoustics can be used to determine temperatures during retinal laser treatments in real-time. This allows evaluating the time-temperature-dependence of retinal coagulation in vivo.},
       keywords = {AutoPhoN},
       url = {http://dx.doi.org/10.1117/12.831877},
       type = {Conference Proceedings}
    }
    
  • Kandulla, J and Elsner, H and Hilmes, M and Hartert, C and Brinkmann, R: Optoacoustic temperature determination at the fundus of the eye during Transpupillary Thermotherapy. in Proc SPIE, no. 5688, pp. 208-214,
    BibTeX
    @inproceedings{Kandulla2005,
       author = {Kandulla, J and Elsner, H and Hilmes, M and Hartert, C and Brinkmann, R},
       title = {Optoacoustic temperature determination at the fundus of the eye during Transpupillary Thermotherapy},
       booktitle = {Proc SPIE},
       volume = {5688},
       pages = {208-214},
       keywords = {AutoPhoN},
       type = {Conference Proceedings}
    }
    
  • Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Luft, Susanne and Baade, Alex and Bever, Marco and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf: Optoacoustic temperature determination and automatic coagulation control in rabbits. in Ophthalmic Technologies XXI, no. 7885, Proc. SPIE,
    BibTeX Link
    @inproceedings{Schlott2011,
       author = {Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Luft, Susanne and Baade, Alex and Bever, Marco and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
       title = {Optoacoustic temperature determination and automatic coagulation control in rabbits},
       booktitle = {Ophthalmic Technologies XXI },
       editor = {Ho, Fabrice Manns; Per G. Söderberg; Arthur},
       publisher = {Proc. SPIE},
       volume = {7885},
       note = {10.1117/12.875104},
       abstract = {Retinal laser photocoagulation is an established treatment method for many retinal diseases like macula edema or diabetic retinopathy. The selection of the laser parameters is so far based on post treatment evaluation of the lesion size and strength. Due to local pigment variations in the fundus and individual transmission the same laser parameters often lead to an overtreatment. Optoacoustic allows a non invasive monitoring of the retinal temperature increase during retinal laser irradiation by measuring the temperature dependent pressure amplitudes, which are induced by short probe laser pulses. A 75 ns/ 523 nm Nd:YLF was used as a probe laser at a repetition rate of 1 kHz, and a cw / 532 nm treatment laser for heating. A contact lens was modified with a ring-shaped ultrasonic transducer to detect the pressure waves at the cornea. Temperatures were collected for irradiations leading to soft or invisible lesions. Based on this data the threshold for denaturation was found. By analyzing the initial temperature increase, the further temperature development during irradiation could be predicted. An algorithm was found to calculate the irradiation time, which is needed for a soft lesion formation, from the temperature curve. By this it was possible to provide a real-time dosimetry by automatically switching off the treatment laser after the calculated irradiation time. Automatically controlled coagulations appear softer and more uniformly.},
       keywords = {AutoPhoN},
       url = {http://dx.doi.org/10.1117/12.875104},
       type = {Conference Proceedings}
    }