Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results.

Selective retina therapy (SRT) is a new laser procedure for retinal diseases that are thought to be associated with a degradation of the retinal pigment epithelium (RPE). The aim of the irradiation is to selectively damage the RPE without affecting the neural retina, the photoreceptors and the choroid. Goal of the treatment is to stimulate RPE cell migration and proliferation into the irradiated areas in order to improve the metabolism at the diseased retinal sites. In a pilot study more than 150 patients with soft drusen, retinopathia centralis serosa (RCS) and macular edema were treated. The first 3-center international trial targets diabetic macular edema and branch vein occlusion. In this review, selective RPE effects are motivated and two modalities to achieve selective RPE effects will be introduced: a pulsed and a continuous wave scanning mode. The mechanism behind selective RPE-effects will be discussed reviewing in vitro results and temperature calculations. So far clinical SRT is performed by applying trains of 30 laser pulses from a Nd:YLF-Laser (527 nm, 1.7 micros, 100 Hz) to the diseased fundus areas. In the range of 450-800 mJ/cm(2) per pulse, RPE-defects in patients were proved angiographically by fluorescein or ICG-leakage. The selectivity with respect to surrounding highly sensitive tissue and the safety range of the treatment will be reviewed. With the laser parameters used neither bleeding nor scotoma, proved by microperimetry, were observed thus demonstrating no adverse effects to the choroid and the photoreceptors, respectively. During and after irradiation, it shows that the irradiated locations are ophthalmoscopically invisible, since the effects are very limited and confined to the RPE, thus a dosimetry control is demanded. We report on a non-invasive opto-acoustic on-line technique to monitor successful RPE-irradiation and compare the data to those achieved with standard angiography one-hour post treatment.

[1]  Kirill V. Larin,et al.  Monitoring of temperature distribution in tissues with optoacoustic technique in real time , 2000, BiOS.

[2]  G. Bresnick.  Diabetic maculopathy. A critical review highlighting diffuse macular edema. , 1983, Ophthalmology.

[3]  R Birngruber,et al.  Retinal sparing by selective retinal pigment epithelial photocoagulation. , 1999, Archives of ophthalmology.

[4]  B. S. Fine,et al.  Retinal repair after experimental xenon arc photocoagulation. I. A comparison between rhesus monkey and rabbit. , 1973, American journal of ophthalmology.

[5]  R Birngruber,et al.  Response of the retinal pigment epithelium to selective photocoagulation. , 1992, Archives of ophthalmology.

[6]  Charles P. Lin,et al.  Targeting of the retinal pigment epithelium (RPE) by means of a rapidly scanned continuous wave (CW) laser beam , 2003, Lasers in surgery and medicine.

[7]  J. Marshall,et al.  Some New Findings on Retinal Irradiation by Krypton and Argon Lasers , 1984 .

[8]  Ralf Brinkmann,et al.  Noninvasive optoacoustic temperature determination at the fundus of the eye during laser irradiation. , 2004, Journal of biomedical optics.

[9]  J. Fujimoto.  Optical coherence tomography for ultrahigh resolution in vivo imaging , 2003, Nature Biotechnology.

[10]  Ralf Brinkmann,et al.  Microbubble dynamics around laser heated microparticles , 2003, European Conference on Biomedical Optics.

[11]  N. Yoshimura,et al.  Increased production of transforming growth factor-beta 2 from cultured human retinal pigment epithelial cells by photocoagulation. , 1994, Investigative ophthalmology & visual science.

[12]  B Paul,et al.  Selective thermal effects with pulsed irradiation from lasers: from organ to organelle. , 1983, The Journal of investigative dermatology.

[13]  M. Figueroa,et al.  LASER PHOTOCOAGULATION FOR MACULAR SOFT DRUSEN: Updated Results , 1997, Retina.

[14]  Ralf Brinkmann,et al.  Interferometric detection of laser-induced microbubbles in the retinal pigment epithelium , 2001, European Conference on Biomedical Optics.

[15]  V. K. Pustovalov.  Thermal processes under the action of laser radiation pulse on absorbing granules in heterogeneous biotissues , 1993 .

[16]  M L Wolbarsht,et al.  The rationale of photocoagulation therapy for proliferative diabetic retinopathy: a review and a model. , 1980, Ophthalmic surgery.

[17]  F Hillenkamp,et al.  Theoretical investigations of laser thermal retinal injury. , 1985, Health physics.

[18]  W. Foulds,et al.  Effect of photocoagulation on the barrier function of the pigment epithelium. II. A study by electron microscopy. , 1977, Transactions of the ophthalmological societies of the United Kingdom.

[19]  M. Latina,et al.  Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions. , 1995, Experimental eye research.

[20]  Kirill V. Larin,et al.  Real-time optoacoustic monitoring of temperature in tissues , 1999, Photonics West - Biomedical Optics.

[21]  M. Mandai,et al.  Photocoagulated human retinal pigment epithelial cells produce an inhibitor of vascular endothelial cell proliferation. , 1995, Investigative ophthalmology & visual science.

[22]  W. Ertmer,et al.  Optoacoustic imaging for optimization of laser cyclophotocoagulation. , 2003, Journal of biomedical optics.

[23]  R.R. Anderson,et al.  Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. , 1983, Science.

[24]  P. Campochiaro,et al.  Retinal pigment epithelial cells release inhibitors of neovascularization. , 1987, Ophthalmology.

[25]  F Hillenkamp,et al.  Microphotocoagulation: selective effects of repetitive short laser pulses. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[26]  W. Heriot,et al.  Pigment epithelial repair , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.

[27]  N. Bülow.  THE PROCESS OF WOUND HEALING OF THE AVASCULAR OUTER LAYERS OF THE RETINA , 1978, Acta ophthalmologica. Supplementum.

[28]  Kirill V. Larin,et al.  Real-time optoacoustic monitoring during thermotherapy , 2000, BiOS.

[29]  Kirill V. Larin,et al.  Real-time optoacoustic monitoring of temperature in tissues , 2005 .

[30]  Ralf Brinkmann,et al.  Selective damage of pigmented cells by means of a rapidly scanned cw laser beam , 2002, SPIE BiOS.

[31]  A. Prosperetti,et al.  Bubble Dynamics and Cavitation , 1977 .

[32]  Charles P. Lin,et al.  Selective cell killing by microparticle absorption of pulsed laser radiation , 1999 .

[33]  Markus W. Sigrist,et al.  Laser‐generated stress waves in liquids , 1978 .

[34]  Ralf Brinkmann,et al.  Optoacoustic measurements during us irradiation of the retinal pigment epithelium , 2000, Photonics West - Biomedical Optics.

[35]  Charles P. Lin,et al.  Microcavitation and cell injury in RPE cells following short-pulsed laser irradiation , 1997, Photonics West - Biomedical Optics.

[36]  T. Flotte,et al.  Stress‐wave‐induced injury to retinal pigment epithelium cells in vitro , 1996, Lasers in surgery and medicine.

[37]  Reginald Birngruber,et al.  Threshold determinations for selective retinal pigment epithelium damage with repetitive pulsed microsecond laser systems in rabbits. , 2002, Ophthalmic surgery and lasers.

[38]  R. Anderson,et al.  Selective thermal effects with pulsed irradiation from lasers: from organ to organelle. , 1983, The Journal of investigative dermatology.

[39]  Horst Kuchling,et al.  Taschenbuch der Physik , 2022 .

[40]  R. Murphy,et al.  Choroidal neovascularization after laser photocoagulation for diabetic macular edema. , 1990, Ophthalmology.

[41]  Reginald Birngruber,et al.  Optoacoustic real-time dosimetry for selective retina treatment. , 2005, Journal of biomedical optics.

[42]  R. Birngruber,et al.  [Histology of retinal lesions after continuous irradiation and selective micro-coagulation of the retinal pigment epithelium]. , 1993, Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft.

[43]  R Birngruber,et al.  Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study , 2000, The British journal of ophthalmology.

[44]  Charles P. Lin,et al.  Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen , 2000, Lasers in surgery and medicine.

[45]  S. Ryan,et al.  SUBRETINAL ENDOPHOTOCOAGULATION: A New Model of Subretinal Neovascularization in the Rabbit , 1991, Retina.

[46]  Victor K. Pustovalov,et al.  Theoretical consideration of the selective thermodenaturation of pigment epithelium layer using short laser pulses , 1994, Photonics West - Lasers and Applications in Science and Engineering.

[47]  Reginald Birngruber,et al.  Thermal Modeling in Biological Tissues , 1980 .

[48]  M. Sigrist.  Laser generation of acoustic waves in liquids and gases , 1986 .

[49]  I. Wallow.  Repair of the pigment epithelial barrier following photocoagulation. , 1984, Archives of ophthalmology.

[50]  Ralf Brinkmann,et al.  Pump-probe detection of laser-induced microbubble formation in retinal pigment epithelium cells. , 2004, Journal of biomedical optics.