Selective Retinal Therapy (SRT) was developed at the Medical Laser Center Lübeck and is currently being evaluated experimentally and clinically as a new, gentle laser treatment method for various diseases of the ocular fundus. In SRT, cells of the retinal pigment epithelium (RPE) are selectively destroyed without affecting the directly adjacent photoreceptors of the retina or the Bruch's membrane and choroid located under the RPE. Among other things, the RPE regulates the entire metabolism at the retina. The aim of the treatment is to significantly improve the metabolism at the retina through the wound healing reaction by regeneration of the RPE and Bruch's membrane. 

Further informations on SRT : mll-luebeck.com/industrieprojekte/selektive-retina-therapie/

A current topic is the realization and clinical testing of an automatic dosage, since the physician cannot optically see the irradiated areas. The dosimetry is based on the detection of intracellular microbubbles, which are responsible for the selective disruption of RPE cells. The bubbles can be detected optically (changing light reflection or OCT) or acoustically (cf. bubbling of the bubbles while boiling water in the tea kettle). In the automatic dosage system currently under investigation, the laser pulse energy per laser spot is increased in a stair-like manner. The laser is then automatically switch off as soon as the bubble formation threshold is exceeded in the pulse energy ramp (see figure).

 

Pulse energy ramp for a SRT spot (a) with acoustical (b) and optical transients (c) colour coded for the same laser spot, exemplary from a clinical trial using both techniques simultaneously. Blue colours represent sub microbubble formation (MBF) energies. Pulse # 8 (light green) first shows clear modulations on both the acoustical and optical transients, respectively, compared to the previous pulses, indicating that the MBF threshold has passed. Orange and red lines denote pulses with strong modulations associated with large and likely coalesced bubbles. In case of an automated feedback, the laser ramp should be ceased with the green or orange pulses to safely stay within the therapeutic window in order to prevent large thermomechanical disruption. This can lead to collateral damage, including bleeding as it has been observed after therapeutic 3 ns laser exposure.

Own peer reviewed publications to SRT:
1.            Seifert E, Tode J, Pielen A, Theisen-Kunde D, Framme C, Roider J, Miura Y, Birngruber R, Brinkmann R. Selective retina therapy: toward an optically controlled automatic dosing. J Biomed Opt 2018; 23(11):1-12.
2.            Yasui A, Yamamoto M, Hirayama K, Kohno T, Theisen-Kunde D, Brinkmann R, Miura Y, Shiraki K. Retinal sensitivity after selective retina therapy (SRT) on patients with central serous chorioretinopathy. Graefe's Archive for Clinical and Experimental Ophthalmology 2016; 255(2):243-254.
3.            Park YG, Kim JR, Kang S, Seifert E, Theisen-Kunde D, Brinkmann R, Roh Y-J. Safety and efficacy of selective retina therapy (SRT) for the treatment of diabetic macular edema in Korean patients. Graefes Archive For Clinical and Experimental Ophthalmology 2016; 254(9):1703-1713.
4.            Kim HD, Jang SY, Lee SH, Kim YS, Ohn Y-H, Brinkmann R, Park TK. Retinal Pigment Epithelium Responses to Selective Retina Therapy in Mouse Eyes. Investigative Ophthalmology & Visual Science 2016; 57(7):3486-3495.
5.            Kang S, Park YG, Kim JR, Seifert E, Theisen-Kunde D, Brinkmann R, Roh YJ. Selective Retina Therapy in Patients With Chronic Central Serous Chorioretinopathy: A Pilot Study. Medicine 2016; 95(3):e2524.
6.            Steiner P, Ebneter A, Berger LE, Zinkernagel M, Povazay B, Meier C, Kowal JH, Framme C, Brinkmann R, Wolf S, Sznitman R. Time-Resolved Ultra-High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina Therapy. Invest Ophthalmol Vis Sci 2015; 56(11):6654-6662.
7.            Park YG, Kang S, Brinkmann R, Roh Y-J. A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation. Journal of ophthalmology 2015; 2015:247259.
8.            Kim HD, Han JW, Ohn Y-H, Brinkmann R, Park TK. Functional Evaluation Using Multifocal Electroretinogram After Selective Retina Therapy With a Microsecond-Pulsed Laser. Investigative Ophthalmology & Visual Science 2015; 56(1):122-131
9.            Framme C, Walter A, Berger L, Prahs P, Alt C, Theisen-Kunde D, Kowal J, Brinkmann R. Selective retina therapy in acute and chronic-recurrent central serous chorioretinopathy. Ophthalmologica 2015; 234(4):177-188.
10.          Park Y-G, Seifert E, Roh YJ, Theisen-Kunde D, Kang S, Brinkmann R. Tissue response of selective retina therapy by means of a feedback-controlled energy ramping mode. Clinical and Experimental Ophthalmology 2014; 42(9):846-855.
11.          Treumer F, Klettner A, Baltz J, Hussain AA, Miura Y, Brinkmann R, Roider J, Hillenkamp J. Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): Towards slowing the macular ageing process. Experimental Eye Research 2012; 97(1):63-72.
12.          Klatt C, Saeger M, Oppermann T, Poerksen E, Treumer F, Hillenkamp J, Fritzer E, Brinkmann R, Birngruber R, Roider J. Selective retina therapy for acute central serous chorioretinopathy. British Journal of Ophthalmology 2011; 95(1):83-88.
13.          Roider J, Liew SHM, Klatt C, Elsner H, Poerksen E, Hillenkamp J, Brinkmann R, Birngruber R. Selective retina therapy (SRT) for clinically significant diabetic macular edema. Graefes Archive for Clinical and Experimental Ophthalmology 2010; 248(9):1263-1272.
14.          Prahs P, Walter A, Regler R, Theisen-Kunde D, Birngruber R, Brinkmann R, Framme C. Selective retina therapy (SRT) in patients with geographic atrophy due to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2010; 248(5):651-658.
15.          Framme C, Walter A, Prahs P, Regler R, Theisen-Kunde D, Alt C, Brinkmann R. Structural changes of the retina after conventional laser photocoagulation and selective retina treatment (SRT) in spectral domain OCT. Curr Eye Res 2009; 34(7):568-579.
16.          Neumann J, Brinkmann R. Self-limited growth of laser-induced vapor bubbles around single microabsorbers. Applied Physics Letters 2008; 93(3).
17.          Framme C, Walter A, Prahs P, Theisen-Kunde D, Brinkmann R. Comparison of Threshold Irradiances and Online Dosimetry for Selective Retina Treatment (SRT) in Patients Treated With 200 Nanoseconds and 1.7 Microseconds Laser Pulses. Lasers in Surgery and Medicine 2008; 40(9):616-624.
18.          Framme C, Schuele G, Kobuch K, Flucke B, Birngruber R, Brinkmann R. Investigation of selective retina treatment (SRT) by means of 8 ns laser pulses in a rabbit model. Lasers in Surgery and Medicine 2008; 40(1):20-27.
19.          Framme C, Roider J, Brinkmann R, Birngruber R, Gabel V-P. Grundlagen und klinische Anwendung der Lasertherapie an der Netzhaut. klin Monatsblätter Augenheilkunde 2008; 225(4):259-268.
20.          Neumann J, Brinkmann R. Nucleation dynamics around single microabsorbers in water heated by nanosecond laser irradiation. Journal of Applied Physics 2007; 101(11).
21.          Framme C, Brinkmann R. Die Selektive Retina Therapie (SRT). Der Augenspiegel 2007; 53G1396(11).
22.          Framme C, Alt C, Schnell S, Sherwood M, Brinkmann R, Lin CP. Selective targeting of the retinal pigment epithelium in rabbit eyes with a scanning laser beam. Invest Ophthalmol Vis Sci 2007; 48(4):1782-1792.
23.          Brinkmann R, Birngruber R. Selektive Retina-Therapie (SRT). Z Med Phys 2007; 17:6-22.
24.          Neumann J, Brinkmann R. Cell disintegration by laser-induced transient microbubbles and its simultaneous monitoring by interferometry. J Biomed Opt 2006; 11(4):041112, 041111-041111.
25.          Klatt C, Elsner H, Porksen E, Brinkmann R, Bunse A, Birngruber R, Roider J. Selektive Retina-Therapie bei Retinopathia centralis serosa mit Pigmentepithelabhebung. Ophthalmologe 2006; 103(10):850-855.
26.          Elsner H, Poerksen E, Klatt C, Bunse A, Theisen-Kunde D, Brinkmann R, Birngruber R, Laqua H, Roider J. Selective retina therapy in patients with central serous chorioretinopathy. Graefes Archive for Clinical and Experimental Ophthalmology 2006; 244(12):1638-1645.
27.          Elsner H, Klatt C, Liew SH, Porksen E, Bunse A, Rudolf M, Brinkmann R, Hamilton RP, Birngruber R, Laqua H, Roider J. Selektive Retina Therapie (SRT) bei Patienten mit diabetischer Makulopathie. Ophthalmologe 2006; 103(10):856-860.
28.          Brinkmann R, Schüle G, Neumann J, Framme C, Porksen E, Elsner H, Theisen-Kunde D, Roider J, Birngruber R. Selektive Retina-Therapie: Methodik, Technik und Online-Dosimetrie. Ophthalmologe 2006; 103(10):839-849.
29.          Brinkmann R, Roider J, Birngruber R. Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results. Bulletin de la Societe belge d'ophtalmologie 2006(302):51-69.
30.          Schuele G, Rumohr M, Huettmann G, Brinkmann R. RPE damage thresholds and mechanisms for laser exposure in the microsecond-to-millisecond time regimen. Investigative Ophthalmology & Visual Science 2005; 46(2):714-719.
31.          Schuele G, Elsner H, Framme C, Roider J, Birngruber R, Brinkmann R. Optoacoustic real-time dosimetry for selective retina treatment. Journal of Biomedical Optics 2005; 10(6).
32.          Neumann J, Brinkmann R. Boiling nucleation on melanosomes and microbeads transiently heated by nanosecond and microsecond laser pulses. J Biomed Optics 2005; 10(2):024001.
33.          Framme C, Roider J, Sachs HG, Brinkmann R, Gabel V-P. Noninvasive Imaging and Monitoring of Retinal Pigment Epithelium Patterns Using Fundus Autofluorescence - Review. Curr Med Imag Rev 2005; 1:89-103.
34.          Framme C, Alt C, Schnell S, Brinkmann R, Lin CP. Selektive Behandlung des RPE unter Verwendung eines gescannten cw-Laserstrahls im Kaninchenmodell. Ophthalmologe 2005; 102(5):491-496.
35.          Alt C, Framme C, Schnell S, Lee H, Brinkmann R, Lin CP. Selective targeting of the retinal pigment epithelium using an acousto-optic laser scanner. J Biomed Opt 2005; 10(6):64014.
36.          Schüle G, Hüttmann G, Framme C, Roider J, Brinkmann R. Noninvasive optoacoustic temperature determination at the fundus of the eye during laser irradiation. Journal of Biomedical Optics 2004; 9(1):173-179.
37.          Roegener J, Brinkmann R, Lin CP. Pump-probe detection of laser-induced microbubble formation in retinal pigment epithelium cells. J Biomedical Optics 2004; 9(2):367-371.
38.          Kracht D, Brinkmann R. Green Q-switched microsecond laser pulses by overcoupled intracavity second harmonic generation. Optics communication 2004; 231:319-324.
39.          Framme C, Schule G, Roider J, Birngruber R, Brinkmann R. Online autofluorescence measurements during selective RPE laser treatment. Graefes Archive For Clinical and Experimental Ophthalmology 2004; 242(10):863-869.
40.          Framme C, Schüle G, Birngruber R, Roider J, Schütt F, Kopitz J, Holz F, Brinkmann R. Temperature dependent fluorescence of A2-E, the main fluorescent lipofuscin component in the RPE. Curr Eye Res 2004; 29(4-5):287-291.
41.          Framme C, Schuele G, Roider J, Birngruber R, Brinkmann R. Influence of pulse duration and pulse number in selective RPE laser treatment. Lasers in Surgery and Medicine 2004; 34(3):206-215.
42.          Roider J, Brinkmann R, Birngruber R. Selective retinal pigment epithelium laser treatment - Theoretical and clinical aspects. In: Fankhauser F, Kwasniewska S, eds. Lasers in Ophthalmology - Basic, Diagnostic and surgical Aspects. The Hague: Kugler Publications. 2003:119-129.
43.          Framme C, Alt C, Schuele G, Brinkmann R, Birngruber R, Lin C. Threshold determinations for selective RPE laser treatment with a laser scanner in rabbits with different scan times in the microsecond regime. Investigative Ophthalmology & Visual Science 2003; 44:U663-U663.
44.          Brinkmann R, Koop N, Ozdemir M, Alt C, Schuele G, Lin CP, Birngruber R. Targeting of the retinal pigment epithelium (RPE) by means of a rapidly scanned continuous wave (CW) laser beam. Lasers in Surgery and Medicine 2003; 32(4):252-264.
45.          Framme C, Schüle G, Brinkmann R, Birngruber R, Roider J. Fundus-Autofluoreszenz nach selektiver RPE-Laserbehandlung bei makulären Erkrankungen. Ophthalmologe 2002; 99(11):854-860.
46.          Framme C, Schuele G, Roider J, Kracht D, Birngruber R, Brinkmann R. Threshold determinations for selective retinal pigment epithelium damage with repetitive pulsed microsecond laser systems in rabbits. Ophthalmic Surgery and Lasers 2002; 33(5):400-409.
47.          Framme C, Brinkmann R, Birngruber R, Roider J. Autofluorescence imaging after selective RPE laser treatment in macular diseases and clinical outcome: a pilot study. British Journal of Ophthalmology 2002; 86(10):1099-1106.
48.          Roider J, Brinkmann R, Wirbelauer C, Laqua H, Birngruber R. Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study. Br J Ophthalmol 2000; 84(1):40-47.
49.          Brinkmann R, Hüttmann G, Rögener J, Roider J, Birngruber R, Lin CP. Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen. Lasers Surg Med 2000; 27(5):451-464.
50.          Roider J, Brinkmann R, Wirbelauer C, Laqua H, Birngruber R. Retinal sparing by selective retinal pigment epithelial photocoagulation. Arch Ophthalmol 1999; 117(8):1028-1034.
51.          Roider J, Brinkmann R, Wirbelauer C, Birngruber R, Laqua H. Variability of RPE reaction in two cases after selective RPE laser effects in prophylactic treatment of drusen. Graefes Arch Clin Exp Ophthalmol 1999; 237(1):45-50.